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Cardiac surgery–associated acute kidney injury (AKI) is associated with increased postoperative morbidity and mortality. Evidence suggests an association between perioperative acetaminophen administration and decreased incidence of postoperative AKI in pediatric cardiac surgery patients; however, an effect in adults is unknown. All patients (n = 6192) undergoing coronary and/or valve surgery with a recorded Society of Thoracic Surgeons (STS) risk score at our institution between 2010 and 2018 were stratified by acetaminophen exposure on the day of surgery using institutional pharmacy records. AKI was determined using the Kidney Disease: Improving Global Outcomes (KDIGO) staging criteria. Logistic regression was used to analyze the association between perioperative acetaminophen and postoperative kidney injury or STS major morbidity. A sensitivity analysis using propensity score matching on the STS predicted risk of renal failure and cardiopulmonary bypass time was performed to account for time bias. Perioperative acetaminophen exposure was associated with lower odds of stage 1 to 3 acute kidney injury (odds ratio [OR], 0.68; 95% CI, 0.56-0.83; P <.001) and decreased prolonged postoperative ventilation (OR, 0.53; 95% CI, 0.37-0.76; P <.001). A sensitivity analysis provided well-balanced (standard mean difference <0.10) groups of 401 pairs, in which acetaminophen was associated with a decreased incidence of postoperative AKI (OR, 0.7; 95% CI, 0.52-0.94; P =.016). Exposure to acetaminophen on the day of surgery was associated with a decreased incidence of AKI in our patients undergoing cardiac surgery. These data serve as a measure of effect size to further explore the therapeutic potential of acetaminophen to reduce postoperative AKI after cardiac surgery and to elucidate the mechanisms involved. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the potential of diffusion kurtosis imaging (DKI) to assess the early renal functional undulation of diabetic mellitus (DM). Fifty-seven Sprague-Dawley (SD) rats were randomly divided into two groups and eventually 48 rats were included in this study: the normal control (CON) group and diabetic mellitus (DM) group. Weeks 0, 4, 8, and 12 after the diabetes model was successfully established, all the rats were scanned on the 3.0T MRI. The DKI derived parameters of renal parenchyma, including fractional anisotropy (FA co , FA me), mean diffusivity (MD co , MD me), and mean kurtosis (MK co , MK me) were measured. Their alteration over time was analyzed and then correlated with urine volume (UV), blood urea nitrogen (BUN), and serum creatinine (Scr) using Pearson correlation analysis. Finally, hematoxylin and eosin (H&E) staining was performed on the kidneys of the two groups. There was a decreasing trend in FA, MK, and MD values over time in diabetic rats. Also, the gradually worsening histological damage of kidneys was noted over time in diabetic rats. The cortical FA and MK values and medullary FA, MK and MD values of diabetic rats were significantly lower than those of controls at most time points after DM induction. In addition, negative correlations were revealed between the BUN and FA co (r = -0.43, p = 0.03) or FA me value (r = -0.49, p = 0.01). The cortical MK value was moderately correlated with UV (r = -0.46, p = 0.03) and BUN (r = -0.55, p = 0.01). The preliminary findings suggest that DKI might be an effective and sensitive tool to assess the early changes of renal function impairment in diabetic rats. The FA values of the cortex and medulla and the MK value of the cortex are sensitive markers in detecting renal injury in diabetic rats. [ABSTRACT FROM AUTHOR]

This article is a review of the highlights of pertinent literature of interest to the congenital cardiac anesthesiologist, and was published in 2022. After a search of the United States National Library of Medicine PubMed database, several topics emerged in which significant contributions were made in 2022. The authors of this manuscript considered the following topics noteworthy to be included in this review—intensive care unit admission after congenital cardiac catheterization interventions, antifibrinolytics in pediatric cardiac surgery, the current status of the pediatric cardiac anesthesia workforce in the United States, and kidney injury and renal protection during congenital heart surgery. [ABSTRACT FROM AUTHOR]

To observe the effect of electroacupuncture at "Zusanli (ST36)" on 5-fluorouracil (5-FU)-induced renal injury in colorectal cancer-bearing mice, and to further investigate its effects on oxidative stress, inflammatory responses, and cell apoptosis in mouse renal tissue. Thirty-five male BALB/c mice were randomly divided into five groups of seven mice each, namely the control, CT26, 5-FU, sham point (SP), and ST36 (which received EA at the "ST36") groups. With the exception of the control group, each group was subjected to establishment of a subcutaneous implantation tumor model using the murine CT26 colorectal cancer cell line. Once the models were successfully established, the 5-FU, SP, and ST36 groups received 5-FU injection solution intraperitoneally at a dose of 5 mg/mL once every three days over a 21-day period. Mice in the SP and ST36 groups additionally received an EA intervention after each intraperitoneal 5-FU injection. EA were performed on mice of the SP group at bilateral sham acupoints and on mice of the ST36 group at the bilateral "ST36" using the continuous wave mode at a frequency of 2 Hz for a duration of 5 min, intervention was administered once every two days for a duration of 21 days. Samples were collected from the mice at the end of the experiment. The pathological morphology of the renal tissue was observed using hematoxylin and eosin (HE) staining; the contents of creatine (Cre), blood urea nitrogen (BUN) and malondialdehyde (MDA), and superoxide dismutase (SOD) activity were measured using biochemical assays; the expression and nuclear translocation of nuclear factor kappa B p65 subunit (NF-κB p65) were measured by immunofluorescence; the expression levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in serum were measured by ELISA; cell apoptosis in renal tissue was detected using the TUNEL assay; and the expression levels of the anti-B-cell lymphoma/leukemia 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3, cleaved caspase-9, and cytochrome C (cyt c) in renal tissue were measured by Western blotting. Compared with the control group, mice of the CT26 group showed a significant increase in serum Cre content (P <0.01), but the difference in BUN content was not statistically significant (P >0.05). HE staining of renal tissue revealed clear structures with normal glomerular and renal tubular morphology. SOD activity was decreased (P <0.01); MDA content was increased, but the increase was not statistically significant (P >0.05). Differences in NF-κB p65 protein expression in the cytoplasm of renal tissue and serum levels of TNF-α, IL-6, and IL-1β were not statistically significant (all P >0.05). Results of immunofluorescent TUNEL staining indicated an absence of significant cell apoptosis. In the renal tissue, Bcl-2 protein expression was slightly increased (P <0.05), and the expression levels of Bax (P <0.01), cleaved caspase-3 (P >0.05), cleaved caspase-9 (P <0.01), and cyt c (P >0.05) were increased. Compared with the CT26 group, mice of the 5-FU group exhibited an increase in Cre (P <0.01) and BUN (P <0.05) content. HE staining of renal tissue revealed the presence of glomerular atrophy and dilated Bowman's capsular spaces. SOD activity was significantly decreased (P <0.01), while the increase of MDA content was not significant (P >0.05). The expression of NF-κB p65 in the nucleus and serum TNF-α, IL-6, and IL-1β levels showed significant increases (P <0.05). The cell apoptosis level was significantly increased. The protein expression of Bcl-2 (P <0.05), Bax (P <0.01), cleaved caspase-9 (P <0.01), and cyt c (P <0.05) was significantly increased. Compared with the 5-FU group, the ST36 group showed decreased serum Cre and BUN levels (both P <0.01). HE staining of renal tissue showed less renal tissue injury and less dilation of renal capsular cavities. SOD activity was significantly higher (P <0.01), while MDA content was lower (P <0.05). Nuclear expression of NF-κB p65 and serum TNF-α (P <0.05), IL-6 (P <0.05), and IL-1β (P <0.01) levels were lower. The cell apoptosis level was decreased relative to the 5-FU group. Bcl-2 protein expression was significantly increased (P <0.01), while the protein expression levels of Bax (P <0.01), cleaved caspase-3 (P <0.01), cleaved caspase-9 (P <0.01), and cyt c (P <0.05) also were reduced. EA at "ST36" attenuated 5-FU-induced renal injury in colorectal cancer-bearing mice. The mechanism may be related to the regulation of renal oxidative stress, alleviation of inflammatory responses, and inhibition of cell apoptosis. [ABSTRACT FROM AUTHOR]

Triclosan (TCS) is a ubiquitous antimicrobial used in daily consumer products. Previous reports have shown that TCS could induce hepatotoxicity, endocrine disruption, disturbance on immune function and impaired thyroid function. Kidney is critical in the elimination of toxins, while the effects of TCS on kidney have not yet been well-characterized. The aim of the present study was to investigate the effects of TCS exposure on kidney function and the possible underlying mechanisms in mice. Male C57BL/6 mice were orally exposed to TCS with the doses of 10 and 100 mg/(kg•day) for 13 weeks. TCS was dissolved in dimethyl sulfoxide (DMSO) and diluted by corn oil for exposure. Corn oil containing DMSO was used as vehicle control. Serum and kidney tissues were collected for study. Biomarkers associated with kidney function, oxidative stress, inflammation and fibrosis were assessed. Our results showed that TCS could cause renal injury as was revealed by increased levels of renal function markers including serum creatinine, urea nitrogen and uric acid, as well as increased oxidative stress, pro-inflammatory cytokines and fibrotic markers in a dose dependent manner, which were more significantly in 100 mg/(kg•day) group. Mass spectrometry-based analysis of metabolites related with lipid metabolism demonstrated the occurrence of lipid accumulation and defective fatty acid oxidation in 100 mg/(kg•day) TCS-exposed mouse kidney. These processes might lead to lipotoxicity and energy depletion, thus resulting in kidney fibrosis and functional decline. Taken together, the present study demonstrated that TCS could induce lipid accumulation and fatty acid metabolism disturbance in mouse kidney, which might contribute to renal function impairment. The present study further widens our insights into the adverse effects of TCS. [Display omitted] [ABSTRACT FROM AUTHOR]

This study used skipjack by-products to produce skipjack trypsin hydrolysate (STH), which was then processed through the Maillard reaction to create its Maillard product, STHMS3 (200–1000 Da). We evaluated STHMS3's protective effects against hyperuricemia-induced renal injury in mice. Utilizing in vivo experiments, network pharmacology, and molecular docking, we explored its protective mechanisms. STHMS3 significantly decreased serum uric acid, creatinine, blood urea nitrogen, and xanthine oxidase (XOD) levels, reduced oxidative stress, and enhanced antioxidant protein levels in kidneys. Network pharmacology analysis showed STHMS3's interaction with multiple targets and pathways, including apoptosis, NF-κB, and TNF signaling pathways, suggesting a multi-level interactive network mechanism. Molecular docking confirmed STHMS3's ability to directly inhibit XOD through hydrogen bond formation. This study highlights the therapeutic potential of food-derived peptides in managing hyperuricemia and protecting renal function. [Display omitted] [ABSTRACT FROM AUTHOR]

• AAI induces a sex- and time-dependent kidney damage in mice. • AAI modulates circadian behavior in vivo and in vitro. • AAI and its bioactive metabolite ALI disturb the renal circadian clock. • Genetic or environmental perturbation of the central clock does not alter AAI-induced renal injury. • Tubular epithelial-specific loss of the core clock gene Bmal1 aggravates AAI nephrotoxicity. Aristolochic acid I (AAI), an emerging biogenic contaminant widely present in Aristolochic plants, has been implicated in the progression of tubulointerstitial disease, known as aristolochic acid nephropathy (AAN). The circadian clock, a vital regulator of organ homeostasis, is susceptible to external chemical cues, including toxins. However, the reciprocal interactions between AAI and the circadian clock remain unexplored. We initially assessed sex- and time-dependent nephropathy and behavioral responses in C57BL/6J mice exposed to AAI. Subsequently, we evaluated changes in the expression of circadian clock genes following treatment with AAI or its bioactive metabolite, aristolactam I, using real-time quantitative PCR and immunoblotting in renal tissues and cells. Additionally, real-time reporter assays were conducted on kidney explants from PER2::Luc knock-in reporter mice and Per2-dLuc / Bmal1-dLuc reporter cell lines. To further elucidate the regulatory role of circadian clocks in AAI-induced nephropathy, mice with global or kidney-specific knockout of Bmal1 , as well as mice subjected to experimental jetlag, were utilized. Our findings revealed a sex-dependent nephrotoxicity of AAI, with males exhibiting greater vulnerability. AAI-induced nephropathy was accompanied by impaired spatial cognitive function, disruptions in free-running locomotor activity, altered renal expression of multiple core clock genes, and disturbances in the circadian rhythm of renal PER2::Luc activity. Notably, kidney-specific ablation of the core clock gene Bmal1 significantly exacerbated renal injury and inflammation, whereas disruptions to the central clock, either genetically (through conventional knockout of Bmal1) or environmentally (mimicking jetlag), had minimal effects on AAI nephrotoxicity. Furthermore, both AAI and its bioactive metabolite aristolactam I demonstrated the ability to disrupt circadian clocks in human osteosarcoma cells (U2OS) and mouse renal tubular epithelial cells (mRTEC). Collectively, these findings highlight the detrimental impact of aristolochic acids on local renal circadian clocks, ultimately exacerbating kidney damage. This study provides novel insights into the molecular mechanisms underlying AAI nephrotoxicity, potentially opening avenues for therapeutic interventions aimed at modulating the renal circadian clock to treat AAN. [Display omitted] [ABSTRACT FROM AUTHOR]

Triptolide (TPL) is a bioactive component extracted from the traditional Chinese herb Tripterygium wilfordii Hook F., and has multiple pharmacological activities, such as anti-tumor activity. However, severe adverse effects and toxicity, especially nephrotoxicity, limit its clinical application. It has been demonstrated that mitochondrial defect is a major toxic effects of TPL. In this study, we show that triptolide activated the cGAS-STING signaling pathway in kidney tubular cells in vivo and in vitro. Renal injury models were established in BALB/c mice and human tubular epithelial cells using TPL. We found that TPL enhanced the phosphorylation levels of STING, TBK1 and IRF3, and upregulated the expression of IFNβ, which is the production of cGAS-STING signaling pathway. STING inhibitor C176 had protective effects in TPL-induced nephrocyte damage. STING siRNA down regulated the expression level of IFNβ. In addition, triptolide induced an increase in protein levels of the transcription factor BACH1, while transcriptional expression of the antioxidant enzyme HMOX1 was reduced due to the increased expression of BACH1. Furthermore, oxidative stress-induced mtDNA damage and DNA leakage caused activation of the cGAS-STING signaling pathway. Altogether, cGAS-STING signaling pathway involved in TPL induced nephrotoxicity. Inhibiting cGAS-STING over-activation may be a new strategy for alleviating renal injury of triptolide. [Display omitted] • Triptolide activates the cGAS-STING signaling pathway in kidney tubular cells in vivo and in vitro. • STING inhibitor C176 had protective effects in TPL-induced nephrocyte damage. • Triptolide induced an enhancement in protein levels of BACH1, while the expression of HMOX1 was reduced. • Oxidative stress-induced mtDNA damage and DNA leakage were the causes of the activation of cGAS-STING signaling pathway. [ABSTRACT FROM AUTHOR]

Simiao Pills, a classical traditional Chinese medicine prescription recorded in Cheng Fang Bian Du , has been traditionally used to treat hyperuricemia due to its heat-clearing and diuretic properties. Studies have shown that Simiao Pills effectively reduce uric acid levels. However, further research is needed to elucidate the precise composition of Simiao Pills for treating hyperuricemia and their potential pharmacological mechanism. This study aimed to investigate the therapeutic effects of Simiao Pills on hyperuricemia, with a particular focus on evaluating their protective role against hyperuricemia-induced renal injury and elucidating the underlying mechanism of action. UPLC-MS/MS was used to identify the components of Simiao Pills. The hyperuricemia model mice were established by intraperitoneal injecting potassium oxonate (PO) and oral administrating hypoxanthine (HX). Network pharmacology, transcriptome, and metabolomics analyses were integrated to explore the mechanism of Simiao Pills in reducing uric acid and protecting the kidney. Mechanistic and functional studies were conducted to validate the potential mechanisms. Simiao Pills were found to contain 12 characteristic components. Treatment with Simiao Pills significantly reduced serum uric acid levels and ameliorated hyperuricemia-induced renal injury. Simiao Pills inhibited the enzymatic activities of XOD and XDH, and regulated the uric acid transporters in the kidney and ileum. Transcriptome and network pharmacology analyses highlighted quercetin, berberine, kaempferol, and baicalein as the principal active components of Simiao Pills acting on the kidney during hyperuricemia treatment, primarily impacting fibrosis, apoptosis, and inflammation-related signaling pathways. Metabolomic analysis unveiled 21 differential metabolites and 5 metabolic pathways associated with Simiao Pills against renal injury associated with hyperuricemia. Further experimental results validated that Simiao Pills reduced renal fibrosis, apoptotic renal cells, serum inflammation levels, and inhibited the NF-κB/NLRP3/IL-1β signaling pathway. This study demonstrated that Simiao Pills significantly reduced serum uric acid levels and improved renal injury by regulating inflammation, apoptosis, and renal fibrosis. These findings have provided a robust scientific pharmacological basis for the use of Simiao Pills in treating hyperuricemia patients. Simiao Pills alleviates renal injury associated with hyperuricemia: A multi-omics analysis. [Display omitted] [ABSTRACT FROM AUTHOR]

Podocytes maintain renal filtration integrity when the glomerular filtration barrier (GFB) is integrated. Impairment or attrition of podocytes, leading to compromised GFB permeability, constitutes the primary etiology of proteinuria and is a hallmark pathological feature of diabetic nephropathy (DN). This study centers on Heterogeneous Nuclear Ribonucleoprotein I (HNRNP I), an RNA-binding protein, delineating its role in facilitating DN-induced renal damage by modulating podocyte health. Comparative analyses in renal biopsy specimens from DN patients and high-glucose-challenged podocyte models in vitro revealed a marked downregulation of HNRNP I expression relative to normal renal tissues and podocytes. In vitro assays demonstrated that high-glucose conditions precipitated a significant reduction in podocyte viability and an escalation in markers indicative of apoptosis. Conversely, HNRNP I overexpression was found to restore podocyte viability and attenuate apoptotic indices. IRAK1, a gene encoding a protein integral to inflammatory signaling, was shown to interact with HNRNP I, which promotes IRAK1 degradation. This interaction culminates in suppressing the PI3K/AKT/mTOR signaling pathway, thereby diminishing podocyte apoptosis and mitigating renal damage in DN. This investigation unveils the mechanistic role of HNRNP I in DN for the first time, potentially informing novel therapeutic strategies for DN renal impairment. [ABSTRACT FROM AUTHOR]

[Display omitted] Hyperuricemia (HUA), recognized as the fourth "high" condition following hypertension, hyperlipidemia, and hyperglycemia, is a metabolic disorder that severely impairs renal function. Spike lavender essential oil (SLEO) exhibits substantial anti-inflammatory and antioxidant activities and can inhibit xanthine oxidase (XOD), suggesting its potential therapeutic potential against HUA. This of this study aimed to analyze the chemical constituents of SLEO with potential efficacy in treating HUA and to explore their mechanisms of action. Gas chromatography-mass spectrometry (GC–MS) combined with a greedy algorithm identified linalool, β-pinene, and β-caryophyllene as key active components of SLEO. Through network pharmacology "weight coefficient" method, the NOD-like signaling pathway emerged as a significant mechanism for SLEO in treating HUA. Investigating an in vitro uric acid (UA)-induced HK-2 cell model revealed that SLEO effectively inhibited the production of IL-1β and IL-18 in the supernatant of HK-2 cells compared to the NLRP3 (antagonist MCC950). Additionally, a HUA rat model demonstrated that SLEO administration significantly reduced hyperuricemia pathological indicators, such as UA, XOD, and blood urea nitrogen (BUN) levels, with renal histopathological sections showing a marked reduction in following SLEO treatment. Metabolomics and transcriptomics analyses further highlighted significant changes in differential metabolites such as arachidonic acid and glycine, as well as the regulation of differential genes such as pycard and PTGS2 in rats. Immunohistochemistry, Western blotting, molecular docking and in vitro XOD activity inhibition assays elucidated the active components mechanisms of SLEO in treating HUA and associated renal inflammation. The findings concluded that SLEO mitigates HUA and renal inflammation by modulating the arachidonic acid metabolic pathway and the NF-κB signaling pathway. Moreover, linalool, β-pinene and β-caryophyllene in SLEO were shown to reduce UA production and lower UA levels in vivo by inhibiting the TLR4/NF-κB/NLRP3 pathway, thereby alleviating HUA-induced renal injury. [ABSTRACT FROM AUTHOR]

Phellinus igniarius is an important medicinal and edible fungus with diverse biological activities. This study aimed to investigate the effects of aqueous extract from P. igniarius (API) on the treatment of hyperuricemia (HUA) and related kidney damage. The chemical constituents of API were determined. The therapeutic effects of API on HUA and renal injury were assessed in adenine/potassium oxonate (PO)-treated mice. The constituent analysis of API revealed a predominance of polysaccharides (33.4 %), followed by total flavonoids (9.1 %), and total triterpenoids (3.5 %). Compared to control, the adenine/PO treatment greatly elevated serum uric acid (UA) levels but this elevation was attenuated by API. In the liver, the expression and activity of xanthine oxidase (XOD) were increased by HUA which were diminished by API. Furthermore, API was found to enhance the expression of UA transporter ABCG2 in the kidney and intestine of HUA mice, suggesting elevating UA excretion. Additionally, API ameliorated HUA-induced renal injury, as indicated by reduced serum BUN/creatinine levels, decreased glomerular and tubular damage, and lowered fibrotic levels. Network pharmacology analysis predicted that P. igniarius may regulate mitochondrial function to improve HUA-related renal injury. This prediction was then substantialized by the API-induced upregulation of NAD+/NADH ratio, ATP level, SOD2 activity, and expression of SOD2/PCG-1α/PPARγ in the kidney of HUA mice. Our results demonstrate that API may effectively ameliorate HUA by reducing UA production in the liver and enhancing UA excretion in the kidney and intestine, and it might be a potential therapy to HUA-related renal injury. [Display omitted] • Aqueous extract of Phellinus igniarius (API) mainly contains total polysaccharides, total flavonoids and total triterpenoids. • API effectively ameliorated hyperuricemia (HUA) by reducing uric acid productionand enhancing UA excretion. • API attenuated HUA-related renal injury by improving the mitochondrial function. [ABSTRACT FROM AUTHOR]

Exposure to environmental contaminants and the development of hypertension and diabetes represent crucial risk factors for chronic kidney disease (CKD). Toxicological studies have revealed that organophosphate esters (OPEs) impair kidney function. However, the joint effects of OPE exposure on kidney injury and the interactions of OPE exposure with hypertension or diabetes on kidney injury remain unclear. Our study aimed to investigate the individual and joint effects of OPE exposure on renal injury, as well as the potential interaction between OPE exposure and hypertension or diabetes on kidney injury. The study enrolled 1938 participants from Wuhan, China. To explore the relationship between OPE exposure and renal injury, we conducted multivariate linear and logistic regression analysis. The results indicated that each unit increase in 4-hydroxyphenyl diphenyl phosphate (4-HO-DPHP), bis(2-butoxyethyl) phosphate (BBOEP), and tris(2-chloroethyl) phosphate (TCEP) (1 μg/L-ln transformed) was associated with a decreased 0.57 mL/min/1.73 m2 (95%CI: -1.05, −0.09), 0.85 mL/min/1.73 m2 (95%CI: -1.52, −0.19) and 1.24 mL/min/1.73 m2 (95%CI: -2.26, −0.23) of estimated glomerular filtration rate (eGFR), while each unit increase in 4-HO-DPHP and BBOEP (1 μg/L-ln transformed) was associated with 14% and 20% elevation of incident impaired renal function (IRF) risk. Notably the highest tertile of BCIPHIPP was positively associated with eGFR, although the p for trend ＞ 0.05. We employed Bayesian kernel machine regression (BKMR) and quartile-based g-computation (qgcomp) models to explore the joint effects of OPE mixtures on eGFR and IRF. Both the results of BKMR and qgcomp model consistently demonstrated negative associations between OPE mixtures and eGFR, and TCEP and 4-HO-DPHP were major contributors. Furthermore, we observed multiplicative interactions of diphenyl phosphate (DPHP), BBOEP, di-ocresyl phosphate (DoCP) & di-p-cresyl phosphate (DpCP), 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) and hypertension or diabetes on kidney injury (all P ＜0.05). Those with diabetes or hypertension and higher OPE metabolite concentrations had increased risk of kidney function impairment compared to those who did not have diabetes or hypertension. These findings suggest that specific OPE exposure may elevate the risk of renal injury, particularly among hypertensive and diabetic populations. [Display omitted] • Urinary 4-HO-DPHP, BBOEP and TCEP were significantly associated with decreased eGFR level. • Urinary 4-HO-DPHP and BBOEP were associated with increased IRF risk. • OPE mixtures were related to decreased eGFR levels. • Significant interactions between OPE exposure and hypertension or diabetes on kidney injury were identified. [ABSTRACT FROM AUTHOR]

Chronic kidney disease is a prevalent and severe significant complication of hypoxia. This study found that peptide LVYPFPGPIPN could protect hypoxia-induced renal injury in the animal model. Network pharmacology and molecular docking analysis indicated that cathepsin B (CTSB) and interleukin-1β (IL-1β) represent potential targets for the prevention/treatment of hypoxic-induced renal injury. GO analysis revealed the involvement of these genes in various biological processes, including apoptosis regulation, oxidative stress response, and adaptive immune modulation. Experimental results in vitro and in vivo demonstrated that peptide LVYPFPGPIPN could effectively inhibit apoptosis and stress responses of kidney cells by regulating the NRF2/IL-1β/mitochondrial apoptosis pathway, thereby protecting hypoxic human embryonic kidney cells from damage. The anti-hypoxic effect of the LVYPFPGPIPN offers a novel therapeutic clue for the treatment/prevention of hypoxic-induced kidney injury and inflammation-associated chronic kidney disease. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Most of the data on high grade Traumatic renal injuries (TRI) has come from centres which predominantly encounter blunt trauma. Blunt and penetrating mechanisms are not analogous, and it is imprudent to blindly extrapolate management strategies between the two groups. In addition, within the broad group of penetrating mechanisms of injury there are also major differences between gunshot wounds (GSW) and stab wounds (SW). The aim of this comparative study of GSW and SW to the kidney is to quantify the impact of the mechanism of injury on nephrectomy rate in high grade TRI.Methods: A prospective trauma registry was interrogated retrospectively. All patients sustaining a high grade (Grade III to V) penetrating TRI were included. The diagnosis was made either with cross-sectional imaging or intra-operative findings. The nephrectomy rate of the different mechanisms of penetrating (GSW vs SW) TRI was compared in each grade.Results: A total of 28 GSW and 27 SW causing high grade TRIs (Grade III-V) were included over the 85 months of the study. GSW lead to a higher nephrectomy rate than SWs 50.0 vs 19%, (p = 0.023). When comparing grade for grade, Grade III: 20.0 (GSW) vs 21% (SW), (p = 1). Grade IV: 71 (GSW) vs 17%, (SW) (p = 0.058) and Grade V: 100 (GSW) vs 0%, (SW) (p = 0.28). When comparing Grade IV - V together, the difference is 85 (GSW) vs 15%, (SW) (p = 0.001).Conclusion: On a grade to grade comparison GSWs have a much higher risk for nephrectomy than SW's in grade IV and V TRI. TRI secondary to GSWs appears to be an independent risk factor for nephrectomy in high grade injuries. The mechanism of penetrating TRI should be considered in future management algorithms and clinical approaches. [ABSTRACT FROM AUTHOR]

Background: Renal injury accounts for 1-5% of all traumatic injuries. Non-operative management (NOM) of renal trauma has demonstrated higher renal salvage rates and reduced morbidity.Aims: The aim of this review is to clarify the indications of early follow up CT scan for adult patients, with NOM, renal trauma, with a view to avoiding unnecessary CT scanning and radiation exposure in this cohort of patients.Methods: A systematic search was conducted using PubMed (MEDLINE), Web of Science, Embase, and Cochrane library, with references from relevant articles also evaluated. Inclusion criteria were defined as studies reporting outcomes of patients ≥12 years of age, with NOM, renal trauma and early CT re-imaging. The outcomes of interest were renal complications requiring intervention, specifically collecting system and vascular complications.Results: Five studies met the inclusion criteria. In total, 542 patients were included in this analysis; study sizes ranged from 48 to 207 patients. Early re-imaging was performed for 510 patients, including 489 CTs and 31 Ultrasounds (US). Mean time to re-imaging ranged from 1 - 35.9 days. Twenty three patients required intervention following re-imaging, all of which were for injuries grade ≥ 3 and presented with clinical deterioration prior to re-imaging, had a collecting system injury identified on initial CT scan or both. The number needed to re-image, in order to change the management of one patient, was 22.Conclusions: Although the findings of this review are based on retrospective data, they suggest routine early re-imaging can be safely omitted for all NOM, renal injuries which remain asymptomatic, with no collecting system injury diagnosed on initial CT, provided appropriate delayed phase imaging is available. Future prospective studies are required to further clarify the indications of early re-imaging, specifically for NOM penetrating injuries, and the appropriate modality and timing of early re-imaging for all NOM renal trauma. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fabrication of Cisplatin (CIS-PT) on conjugations of linoleic acid by nanoassembly (CIS-PT-NPs). • The in vitro antiproliferative activity shows CIS-PT-NPs induced apoptosis in renal cancer cells. • The morphological examinations of CIS-PT-NPs have studied AO/EB and nuclear staining methods. • The cell death of CIS-PT-NPs was confirmed by flow cytometry analysis. • The In vivo toxicity results displays the CIS-PT-NPs remarkably alleviated the toxicity compared to CIS-PT. Renal cell carcinoma (RCC) is a widespread type of urological tumor that derives from the highly heterogeneous epithelium of the kidney tissue. For the past decade, the treatment of kidney cancer cells has changed clinical care for RCC. Herein, we present a very easy and cost-effective method that incorporates tumor-specific targeting supramolecular nanoassembly, and therapeutically to overcome the different challenges raised by the distribution of the pharmaceutical potential anticancer drug Cisplatin (CIS-PT). On covalent conjugations of hydrophobic linoleic acid by carboxylic group, the CIS-PT prodrugs were skilled in impulsively nanoassembly into extremely steady nanoparticles size (∼100 nm). Electron microscopic techniques have verified the newly synthesized morphology of CIS-PT-NPs. The anticancer properties of CIS-PT and CIS-PT-NPs against Caki-1 and A-498 (renal carcinoma) cancer cell lines have been evaluated after successful synthesis. Other research, such as dual staining acridine orange/ethidium bromide (AO–EB), Hoechst 33,344 and flow cytometry study on the apoptosis mechanisms, have shown that proliferation in renal cancer cells is associated with apoptosis. Further the In vivo toxicity results displays the CIS-PT-NPs remarkably alleviated the toxicity of the potential anticancer drug CIS-PT In vivo while conserving the Pharmaceutical activity. Compared to CIS-PT, CIS-PT-NPs demonstrate excellent In vitro and In vivo property, this study clarified the CIS-PT-NPs as a healthy and positive RCC care chemotherapeutics technique and deserve further clinical evaluations. [ABSTRACT FROM AUTHOR]

Burst wave lithotripsy (BWL) is a technology under clinical investigation for non-invasive fragmentation of urinary stones. Under certain ranges of ultrasound exposure parameters, this technology can cause cavitation in tissue leading to renal injury. This study sought to measure the focal pressure amplitude needed to cause cavitation in vivo and determine its consistency in native tissue, in an implanted stone model and under different exposure parameters. The kidneys of eight pigs were exposed to transcutaneous BWL ultrasound pulses. In each kidney, two locations were targeted: the renal sinus and the kidney parenchyma. Each was exposed for 5 min at a set pressure level and parameters, and cavitation was detected using an active cavitation imaging method based on power Doppler ultrasound. The threshold was determined by incrementing the pressure amplitude up or down after each 5-min interval until cavitation occurred/subsided. The pressure thresholds were remeasured postsurgery, targeting an implanted stone or collecting space (in sham). The presence of a stone or sham surgery did not significantly impact the threshold for tissue cavitation. Targeting parenchyma instead of kidney collecting space and lowering the ultrasound pulse repetition frequency both resulted in an increased pressure threshold for cavitation. [ABSTRACT FROM AUTHOR]

Arsenic (As) is a heavy metal known for its detrimental effects on the kidneys, but the precise mechanisms underlying its toxicity remain unclear. In this study, we employed an integrated approach combining traditional toxicology methods with functional metabolomics to explore the nephrotoxicity induced by As in mice. Our findings demonstrated that after 28 days of exposure to sodium arsenite, blood urea nitrogen, serum creatinine levels were significantly increased, and pathological examination of the kidneys revealed dilation of renal tubules and glomerular injury. Additionally, uric acid, total cholesterol, and low-density lipoprotein cholesterol levels were significant increased while triglyceride level was decreased, resulting in renal insufficiency and lipid disorders. Subsequently, the kidney metabolomics analysis revealed that As exposure disrupted 24 differential metabolites, including 14 up-regulated and 10 down-regulated differential metabolites. Ten metabolic pathways including linoleic acid and glycerophospholipid metabolism were significantly enriched. Then, 80 metabolic targets and 168 predicted targets were identified using metabolite network pharmacology analysis. Of particular importance, potential toxicity targets, such as glycine amidinotransferase, mitochondrial (GATM), and nitric oxide synthase, and endothelial (NOS3), were prioritized through the "metabolite-target-pathway" network. Receiver operating characteristics curve and molecular docking analyses suggested that 1-palmitoyl-2-myristoyl-sn-glycero-3-PC, linoleic acid, and L-hydroxyarginine might be functional metabolites associated with GATM and NOS3. Moreover, targeted verification result showed that the level of linoleic acid in As group was 0.4951 μg/mL, which was significantly decreased compared with the control group. And in vivo and in vitro protein expression experiments confirmed that As exposure inhibited the expression of GATM and NOS3. In conclusion, these results suggest that As-induced renal injury may be associated with the inhibition of linoleic acid metabolism through the down-regulation of GATM and NOS3, resulting in decreased levels of linoleic acid, 1-palmitoyl-2-myristoyl-sn-glycero-3-PC, and L-hydroxyarginine metabolites. [Display omitted] • Linoleic acid metabolism was inhibited by Arsenic in renal injury mice. • Linoleic acid and L-hydroxyarginine were the potential functional metabolites. • The GATM and NOS3 may be the toxic targets in As-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

Diclofenac (DIC) is a Nonsteroidal anti-inflammatory drug (NSAID) and consumption of this drug creates side effects such as renal injury. The purpose of this work was to assess the influences of gallic acid (GA) on DIC-induced renal injury in rats. Rats were segregated into five groups. Group 1, control group; Group 2 received DIC-only (50 mg/kg bw, i.p.) for 7 consecutive days; Groups 3, received GA-only (100 mg/kg bw, po) for 7 consecutive days; group 4 received DIC (50 mg/kg bw, i.p.) plus GA (50 mg/kg, po) for 7 consecutive days and group 5 received DIC (50 mg/kg bw, i.p.) plus GA (100 mg/kg, po) for 7 consecutive days. The data indicated that the levels of the serum protein carbonyl, sGOT, sGPT, urea, creatinine, uric acid, nitrite content, MDA, serum IL-1β, and the renal IL-1β gene expression were remarkably increased in DIC-only treated animals compared to control group. In the other hand, treatment with gallic acid led to significant improvements in abnormalities of DIC-induced oxidative stress and serum biochemical parameters. Histological changes were also ameliorated by GA oral administration. The results indicated that oral injection of GA could alleviate the noxious effects of DIC on the antioxidant defense system and renal tissue. [ABSTRACT FROM AUTHOR]

Ginsenoside Rb1 (Gs-Rb1) is among the most significant effective pharmacological components in ginseng. 3-monochloropropane-1,2-diol (3-MCPD), a chloropropanol-like contaminant, is produced in the production of refined oils and thermal processing of food. Pyroptosis is a type of programmed cell death triggered by inflammasomes. Excessive pyroptosis causes kidney injury and inflammation. Previous studies have revealed that 3-MCPD induced pyroptosis in mice and NRK-52E cells. In the present study, we find that Gs-Rb1 attenuates 3-MCPD-induced renal cell pyroptosis by assaying GSDMD-N, caspase-1, IL-18, and IL-1β in mice and NRK-52E cells. In further mechanistic studies, we show that Gs-Rb1 removes damaged mitochondria via mitophagy and reduces intracellular reactive oxygen species (ROS) generation, therefore alleviating 3-MCPD-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) activation and pyroptosis. The above results are further validated by the addition of autophagy inhibitor Chloroquine (CQ) and mitophagy inhibitor Cyclosporin A (CsA). Afterward, we explore how Gs-Rb1 activated mitophagy in vitro. We determine that Gs-Rb1 enhances the protein expression and nuclear translocation of Transcription factor EB (TFEB). However, silencing of the TFEB gene by small interfering RNA technology reverses the role of Gs-Rb1 in activating mitophagy. Therefore, we conclude that 3-MCPD damages mitochondria and leads to ROS accumulation, which causes NLRP3 activation and pyroptosis in ICR mice and NRK-52E cells, while Gs-Rb1 mitigates this phenomenon via the TFEB-mitophagy pathway. Our findings may provide new insights for understanding the molecular mechanisms by which Gs-Rb1 mitigates renal injury. [Display omitted] [ABSTRACT FROM AUTHOR]

Recent studies suggest a potential role of bioactive lipids in acute kidney injury induced by lipopolysaccharide (LPS). The current study was designed to determine the profiling activities of various polyunsaturated fatty acid (PUFA) metabolizing enzymes, including lipoxygenases (LO), cyclooxygenase, and cytochrome P450 in the plasma of LPS-injected mice using LC-MS. Heat map analysis revealed that out of 126 bioactive lipids screened, only the 12/15-LO metabolite, 12-HETE, had a significant (2.24 ± 0.4) fold increase relative to control (P = 0.0001) after Bonferroni Correction (BCF α = 0.003). We then determined the role of the 12/15-LO in LPS-induced acute kidney injury using genetic and pharmacological approaches. Treatment of LPS injected mice with the 12/15-LO inhibitor, baicalein, significantly reduced levels of renal injury and inflammation markers including urinary thiobarbituric acid reactive substance (TBARs), urinary monocyte chemoattractant protein-1 (MCP-1), renal interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Similarly, knocking-out of 12/15-LO reduced levels of renal inflammation and injury markers elicited by LPS injection. Next, we tested whether exogenous supplementation with docosahexaenoic acid (DHA) as a substrate would divert the role of 12/15-LO from being pro-inflammatory to anti-inflammatory via increased production of the anti-inflammatory metabolite. DHA treatment restored the decreased in plasma level of resolvin D2 (RvD2) and reduced renal injury in LPS-injected mice whereas DHA treatment failed to provide any synergistic effects in reducing renal injury in LPS injected 12/15-LO knock-out mice. The ability of RvD2 to protect kidney against LPS-induced renal injury was further confirmed by exogenous RvD2 which significantly reduced the elevation in renal injury in LPS injected mice. These data suggest a double-edged sword role of 12/15-LO in LPS-induced acute renal inflammation and injury, depending on the type of substrate available for its activity. [ABSTRACT FROM AUTHOR]

We investigated the gut–kidney interaction in goslings with gout and tried to decipher the probable mechanisms through which gut dysbiosis leads to the progression of renal injury and inflammation. A total of 15 goslings (Anser cygnoides), with typical visceral gout symptoms, were screened and compared with 15 healthy goslings. We determined the signatures of the microbiome in the cecum chyme of goslings in the 2 groups by 16S sequencing, and analyzed the changes in intestinal permeability, levels of serum lipopolysaccharide (LPS), and the induced inflammatory response of Toll-like receptors (TLRs). We found the existence of gut dysbiosis in goslings with gout as a result of interactions among the multitude of bacteria present in the gut, and the proliferation of a specific pathogenic genus, Proteobacteria, played a decisive role in this process. Moreover, the permeability increased not only in the intestinal epithelium but also in the renal endothelium, providing possibilities for gut-derived LPS to enter the blood circulation and damage the kidneys. The systemic LPS concentration was increased in the gout group and exhibited a positive correlation with the degree of renal injury. In addition, we also found that inflammatory disorders concurrently existed in the gut and kidney of goslings with gout, and the LPS/TLR4/MyD88 (Myeloid differentiation primary response gene 88) inflammatory signaling was activated. These results indicate that the loss of intestinal barrier as a result of gut dysbiosis causes the translocation of gut-derived LPS, which can play an important role in the development of gout in goslings through interference with kidney functions. [ABSTRACT FROM AUTHOR]

Bupleurum polysaccharides (BPs) is isolated from Bupleurum smithii var. parvifolium , a key traditional Chinese medicine. The study was to investigate the effects of BPs on diabetic kidney injury. After two intraperitoneal injections of streptozotozin (STZ) 100 mg·kg−1, renal injury in diabetic mice was induced and BPs was orally administrated at dosages of 30 and 60 mg·kg−1·d−1. The STZ injected mice developed renal function damage, renal inflammation and fibrosis known as diabetic kidney disease (DKD). BPs significantly reduced serum creatinine level and urinary albumin excretion rate, with the attenuated swelling of kidneys. BPs treatment obviously alleviated the pathological damage of renal tissue. The progression of renal injury in BPs treated mice was inhibited with less expression of type IV collagen (Col IV), fibronectin (FN) and α -smooth muscle actin (α -SMA). The inhibition of inflammation in kidney was associated with the reduced level of tumor necrosis factor- α (TNF- α) and interleukin-6 (IL-6). BPs administration suppressed the over-expression of toll like receptor 4 (TLR4) and high-mobility group box 1 (HMGB1) with lowered activity of nuclear factor kappa B (NF- κ B) in renal tissue of diabetic mice. Oral administration of BPs effectively prevented the development ofrenal injury in diabetic mice. This study suggested that the protection provided by BPs might affect through the interruption of HMGB1-TLR4 pathway, leading to the inhibition of renal inflammation and fibrotic process. [ABSTRACT FROM AUTHOR]

• Mortality in patients requiring renal replacement therapy is lower than reported. • AKI in major burns is associated with worse outcomes. • Independent risk factors for AKI are TBSA burned, age, and APACHE II score. Acute kidney injury (AKI) is common in major burn injuries and associated with increased mortality. With advances in surgical and critical care it is unclear if mortality in this population remains this high. This study aims to describe incidence and outcomes of patients admitted to intensive care (ICU) with a burn injury who develop AKI. We additionally sought to determine risk factors for developing AKI. A historical cohort study of patients admitted to ICU from 2010 to 2016 with major burn injury was conducted. Demographic, laboratory, and clinical information was collected. AKI was defined by Acute Kidney Injury Network (AKIN) classification. Multivariable logistic regression was used to model association between baseline risk factors and risk of AKI. Of the 151 patients included, 64 people developed AKI (42%) defined by stages 1–3 of AKIN criteria. The median TBSA was 20% (IQR 9–41). Renal replacement therapy was required in 18/64 (28%) who developed AKI. Multivariable logistic regression demonstrated association between AKI and the following variables: APACHE II score (OR 1.2, 95%CI 1.1–1.3, P = 0.001), age (OR 1.8 per 10-year increase, 95%CI: 1.2–2.5, P = 0.002) and log(TBSA). Fractional polynomial regression analysis demonstrates that the best functional form of TBSA was in the natural logarithm (OR 2.7, 95%CI: 1.5–4.7, p = 0.001). Compared to those without AKI, patients with AKI had longer duration of mechanical ventilation, (median 11 [IQR 6–19] vs. 4 [IQR 2–9] days), ICU stay (15 [IQR 9–22] vs. 6 [IQR 3–10] days), and increased mortality (14 of 64(22%) vs. 4 of 87(5%). AKI is common in patients with a major burn injury. However, mortality is lower than described in the literature, particularly for those who required renal replacement therapy. [ABSTRACT FROM AUTHOR]

The American Pediatric Surgical Association (APSA) guidelines for the treatment of isolated solid organ injury (SOI) in children were published in 2000 and have been widely adopted. The aim of this systematic review by the APSA Outcomes and Evidence Based Practice Committee was to evaluate the published evidence regarding treatment of solid organ injuries in children. A comprehensive search strategy was crafted and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were utilized to identify, review, and report salient articles. Four principal questions were examined based upon the previously published consensus APSA guidelines regarding length of stay (LOS), activity level, interventional radiologic procedures, and follow-up imaging. A literature search was performed including multiple databases from 1996 to 2016. LOS for children with isolated solid organ injuries should be based upon clinical findings and may not be related to grade of injury. Total LOS may be less than recommended by the previously published APSA guidelines. Restricting activity to grade of injury plus two weeks is safe but shorter periods of activity restriction have not been adequately studied. Prophylactic embolization of SOI in stable patients with image-confirmed arterial extravasation is not indicated and should be reserved for patients with evidence of ongoing bleeding. Routine follow-up imaging for asymptomatic, uncomplicated, low-grade injured children with abdominal blunt trauma is not warranted. Limited data are available to support the need for follow-up imaging for high grade injuries. Based upon review of the recent literature, we recommend an update to the current APSA guidelines that includes: hospital length of stay based on physiology, shorter activity restrictions may be safe, minimizing post-injury imaging for lower injury grades and embolization only in patients with evidence of ongoing hemorrhage. Systematic Review. Levels 2–4. [ABSTRACT FROM AUTHOR]

Limitation of widely used anti-cancer agent cisplatin for a patient is nephrotoxicity. Nephrotoxicity is presentable in mice by injecting cisplatin at 25 mg/kg with 3 days endpoint. We used the same model to understand the protective role of urolithin A. Cisplatin-induced renal damages measured by histological damage in proximal tubular cells and by the increase in serum neutrophil gelatinase-associated lipocalin (NGAL), blood urea nitrogen (BUN), creatinine and urinary Kidney Injury Molecule-1 (KIM-1). Urolithin A pretreatment reduced all the above renal damage parameters in a significant way. Urolithin A attenuated cisplatin-induced pro-inflammatory cytokine/chemokine tumor necrosis factor α (TNFα), interleukin 23 (IL-23), interleukin 18 (IL-18) and macrophage inflammatory protein 2 (MIP2). Cisplatin-induced CD11b positive macrophages in kidneys reduced by urolithin A. Urolithin A also attenuated cisplatin-induced renal oxidative/nitrative stress, which was measured by lipid peroxidation(4-hydroxy-2-nonenal or 4-HNE protein adducts) and protein nitration. Urolithin A cisplatin-induced kidney injury in mice through the down regulation of inflammatory cytokines/chemokine, immune cells, and oxidative/nitrative stress thus improving cisplatin-induced proximal tubular cell death. [ABSTRACT FROM AUTHOR]

Background: Intraoperative mortality is now rare, but death within 30 days of surgery remains surprisingly common. Perioperative myocardial infarction is associated with a remarkably high mortality. There are strong associations between hypotension and myocardial injury, myocardial infarction, renal injury, and death. Perioperative arterial blood pressure management was thus the basis of a Perioperative Quality Initiative consensus-building conference held in London in July 2017.Methods: The meeting featured a modified Delphi process in which groups addressed various aspects of perioperative arterial pressure.Results: Three consensus statements on intraoperative blood pressure were established. 1) Intraoperative mean arterial pressures below 60-70 mm Hg are associated with myocardial injury, acute kidney injury, and death. Injury is a function of hypotension severity and duration. 2) For adult non-cardiac surgical patients, there is insufficient evidence to recommend a general upper limit of arterial pressure at which therapy should be initiated, although pressures above 160 mm Hg have been associated with myocardial injury and infarction. 3) During cardiac surgery, intraoperative systolic arterial pressure above 140 mm Hg is associated with increased 30 day mortality. Injury is a function of arterial pressure severity and duration.Conclusions: There is increasing evidence that even brief durations of systolic arterial pressure <100 mm Hg and mean arterial pressure <60-70 mm Hg are harmful during non-cardiac surgery. [ABSTRACT FROM AUTHOR]

Abstract Marine toxins are known among several causes of toxin induced renal injury. Enzymatic mechanism by phospholipase A 2 is responsible for acute kidney injury (AKI) in sea snake envenoming without any change in cardiac output and systemic vascular resistance. Cnidarian toxins form pores in the cell membrane with Ca influx storm resulting in cell death. Among plankton toxins domoic acid, palytoxin and maitotoxin cause renal injury by ion transport into the cell through ion channels resulting in renal cell swelling and lysis. Okadaic acid, calyculin A, microcystin LR and nodularin cause AKI by serine threonine phosphatase inhibition and hyperphosphorylation with increased activity of Ca2+/calmodulin – dependent protein kinase II, increased cytosolic Ca2+, reactive oxygen species, caspase and P53. Renal injury by plankons is mostly subclinical and requires sensitive biomarker for diagnosis. In this respect repeated consumption of plankton toxin contaminated seafood is a risk of developing chronic renal disease. The subject deserves more clinical study and scientific attention. Highlights • Renal injury by marine toxins of sea snakes, cnidarians and planktons and the mechanisms are discussed. • Some plankton toxins can cause renal injury. • Renal injury associated with plankton toxin contaminated seafood can be subclinical. • Frequent contaminated seafood consumption may possibly lead to chronic renal disease in the long run. • Looking toward future with global changes awareness, attention and clinical study with sensitive urinary biomarkers are required in this area. [ABSTRACT FROM AUTHOR]

Background: Rhabdomyolysis is a medical condition caused by muscle breakdown leading to potential renal damage. This can result in significant morbidity and mortality if not rapidly identified and treated.Objective: This article provides an evidence-based narrative review of the diagnosis and management of rhabdomyolysis, with focused updates for the emergency clinician.Discussion: Rhabdomyolysis is caused by the breakdown of muscle cells leading to the release of numerous intracellular molecules, including potassium, calcium, phosphate, uric acid, and creatinine kinase. There are a number of potential etiologies, including exertion, extreme temperature changes, ischemia, infections, immobility, drugs, toxins, endocrine causes, autoimmune reactions, trauma, or genetic conditions. Findings can include myalgias, muscle weakness, or dark-colored urine, but more often include non-specific symptoms. The diagnosis is often determined with an elevated creatinine kinase greater than five times the upper-limit of normal. Severe disease may result in renal failure, electrolyte derangements, liver disease, compartment syndrome, and disseminated intravascular coagulation. Treatment includes addressing the underlying etiology, as well as aggressive intravenous hydration with a goal urine output of 300 mL/h. Bicarbonate, mannitol, and loop diuretics do not possess strong evidence for improved outcomes. Renal replacement therapy should be determined on a case-by-case basis. Most patients are admitted, though some may be appropriate for discharge.Conclusion: Rhabdomyolysis is a potentially dangerous medical condition requiring rapid diagnosis and management that may result in significant complications if not appropriately identified and treated. Emergency clinician knowledge of this condition is essential for appropriate management. [ABSTRACT FROM AUTHOR]

Uric acid (UA) is the final metabolite of purines in the liver that can cause hyperuricemia at high levels. The kidneys are the main excretory organs for UA. The excessive accumulation of UA in the kidneys causes the development of hyperuricemia that often leads to renal injury. Eupatilin (Eup) is a flavonoid natural product that possesses various pharmacological properties such as antioxidant, anti-cancer, and anti-inflammatory. We were interested in exploring the potential role of Eup in lowering UA and nephroprotective. We initially investigated the effects of Eup on xanthin oxidase (XOD) activity in vitro, followed by investigating its ability to lower UA levels, anti-inflammatory effects, nephroprotective effects, and the underlying mechanisms using hyperuricemia rats sustained at high UA level. The results showed that Eup had an inhibitory effect on XOD activity in vitro and significantly reduced serum UA, creatinine, BUN, IL-1β and IL-6 levels in hyperuricemic rats, ameliorating inflammation, renal oxidative stress and pathological injury. Furthermore, Eup inhibited ADA and XOD enzyme activities in the liver and serum and modulated GLUT9, URAT1 and ABCG2 protein expression in the kidneys and ileum. Our findings provide a scientific basis for suggesting Eup as an option for a potential treatment for hyperuricemia. • Eupatilin (Eup) significantly reduced serum uric acid in hyperuricemic rats. • ADA and XOD enzyme activities were inhibited by Eup. • Eup ameliorated inflammation, renal oxidative stress and pathological injury. • Eup down-regulated URAT1, GLUT9 and up-regulated ABCG2 protein in the kidney and ileum. [ABSTRACT FROM AUTHOR]

The pathogenesis of immunoglobulin A nephropathy (IgAN) is closely related to immunity and inflammation. The clinical process of IgAN varies greatly, making the assessment of prognosis challenging and limiting progress on effective treatment measures. Autophagy is an important pathway for the development of IgAN. However, the role of autophagy in IgAN is complex, and the consequences of autophagy may change during disease progression. In the present study, we evaluated the dynamic changes in autophagy during IgAN. Specifically, we examined autophagy in the kidney of a rat model of IgAN at different time points. We found that autophagy was markedly and persistently induced in IgAN rats, and the expression level of inflammation was also persistently elevated. The autophagy enhancer rapamycin and autophagy inhibitor 3-methyladenine were used in this study, and the results showed that 3-methyladenine can alleviate renal injury and inflammation in IgAN rats. Our study provides further evidence for autophagy as a therapeutic target for IgAN. • In a rat model of IgAN, autophagy was markedly and persistently induced. • The expression level of inflammation also elevated persistently. • Autophagy inhibitor 3-methyladenine could alleviate renal injury and inflammation in IgAN rats. • The persistent activation of autophagy in IgAN rats in this study was excessive and detrimental. • Autophagy was a therapeutic target for IgAN. [ABSTRACT FROM AUTHOR]

Traditional Chinese Medicine (TCM) Compound Shizhifang (SZF), consisting of the seeds of four Chinese herbs, has been used in Shanghai Shuguang Hospital in China for more than 20 years and has proven its clinical safety and efficacy in lowering uric acid and protecting kidney function. Hyperuricemia (HUA)-induced pyroptosis of renal tubular epithelial cells serves as a significant cause of tubular damage. SZF proves to be effective in alleviating renal tubular injury and inflammation infiltration of HUA. However, the inhibiting effect of SZF on pyroptosis in HUA still remains elusive. This study aims to verify whether SZF could ameliorate pyroptosis in tubular cells induced by uric acid (UA). Quality control analysis and chemical and metabolic identification for SZF and SZF drug serum were performed by using UPLC-Q-TOF-MS. In vitro, human renal tubular epithelial cells (HK-2) stimulated by UA were treated with SZF or NLRP3 inhibitor (MCC950). HUA mouse models were induced by intraperitoneal injection of potassium oxonate (PO). Mice were treated with SZF, allopurinol or MCC950. We focused on evaluated the effect of SZF on the NLRP3/Caspase-1/GSDMD pathway, renal function, pathologic structure and inflammation. SZF significantly restrained the activation of the NLRP3/Caspase-1/GSDMD pathway in vitro and in vivo induced by UA. SZF was better than allopurinol and MCC950 in reducing pro-inflammatory cytokine levels, attenuating tubular inflammatory injury, inhibiting interstitial fibrosis and tubular dilation, maintaining tubular epithelial cell function, and protecting kidney. Furthermore, 49 chemical compounds of SZF and 30 metabolites in serum after oral administration were identified. SZF inhibits UA-induced renal tubular epithelial cell pyroptosis via by targeting NLRP3 to inhibit tubular inflammatory and prevent the progression of HUA-induced renal injury effectively. [Display omitted] • The protective effect of SZF against HUA-induce renal injury. • NLRP3/Caspase-1/GSDMD pathway is involved in the therapeutic effect of SZF on HUA. • SZF inhibit pyroptosis of renal tubular epithelial in HUA mice. • SZF ameliorates inflammatory injury in renal of HUA mice. • SZF improve renal function and tubular functions in HUA mice. [ABSTRACT FROM AUTHOR]

Abstract Apigenin (API) is a kind of important flavonoid present in temperate and tropical fruit and vegetables, especially the celery. It exerts anticancer, anti-bacterial, anti-viral, anti-inflammatory, anti-oxidation properties. In the present study, the mechanism of protective action of apigenin on 3-chloro-1, 2-propanediol (3-MCPD)-induced renal injury was investigated in rat. Sprague-Dawley (SD) rats were divided into five groups: control group (ultrapure water treated), CMC group (sodium carboxymethylcellulose treated), 3-MCPD treatment group (30 mg/kg body weight/day), 3-MCPD plus API co-treatment group (20, 40 mg/kg body weight/day). The results showed that API significantly reduced renal function markers, serum creatinine and urea nitrogen content. Besides, the renal tissue lesion in 3-MCPD treatment group was restored by API to some extent. We indicated that API exerted renoprotective effect by modulating oxidative phosphorylation especially up-regulated the expressions of ATP6 and ATP8, re-establishing mitochondrial membrane potential (MMP), relieving the increase of Bax/Bcl2 ratio, reducing cytochrome c release, thus inhibiting the activation of Caspase 9 and Caspase 3. In conclusion, apigenin possesses excellent protective effect against 3-MCPD-induced renal injury by modulating mitochondria dependent Caspase cascade pathway. Highlights • Apigenin attenuated 3-MCPD-induced renal injury in vitro. • Apigenin inhibited 3-MCPD-induced disorder of oxidative phosphorylation. • Apigenin protected against 3-MCPD-indcued renal injury via mitochondria dependent Caspase cascade pathway. [ABSTRACT FROM AUTHOR]

Abstract The widely used Di-(2-ethylhexyl) phthalate (DEHP) has been reported to exhibit ubiquitous environmental and global health hazards. The bioaccumulation and environmental persistence of DEHP can cause serious health hazards in wildlife animals and human. However, DEHP-induced nephrotoxicity in bird is remained unknown. Thus, this study explored the related mechanism of DEHP nephrotoxicity in quail. For this purpose, quail were exposed with DEHP at doses of 0, 250, 500, and 1000 mg/kg body weight daily by gavage administration for 45 days. The results showed that DEHP exposure induced renal injury, oxidative stress, and endoplasmic reticulum (ER) degeneration. Low level DEHP (250 mg/kg) exposure inhibited Nrf2 signaling pathway and induced renal injury via oxidative stress and suppressed the unfolded protein response (UPR) signaling pathway and induced ER stress in the kidney. But surprisingly, high level DEHP (500 mg/kg and 1000 mg/kg) exposure activated Nrf2 and UPR signaling pathways and protected kidney, but they still couldn't resist the toxicity of DEHP. Our study demonstrated that DEHP-induced nephrotoxicity in quail was associated with activating Nrf2-mediated antioxidant defense response and UPR signaling pathway. Graphical abstract DEHP exposure induced renal injury and destroyed the pathophysiological integrity of the kidney in quail. DEHP-induced nephrotoxicity is associated with oxidative stress, which could be regulated by Nrf2-mediated defense response. DEHP exposure activated the UPR signaling pathway to prevent ER stress in the kidney. Image 1 Highlights • DEHP-induced nephrotoxicity is associated with oxidative stress. • DEHP activates Nrf2 signaling pathway in the kidney. • DEHP-induced nephrotoxicity triggers renal ER stress. • DEHP activates UPR in the kidney. • DEHP induces crosstalk between UPR and Nrf2-mediated antioxidant defense in renal injury. DEHP-induced nephrotoxicity is associated with crosstalk between activated UPR and Nrf2-mediated antioxidant defense mechanism. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) have progressive renal fibrosis, inflammation, and reduced muscle mass and strength. Resistance training (RT) has been suggested to mitigate the loss of muscle mass, of strength and the inflammation in CKD, but the mechanisms are unknown. The aim of this study was to evaluate the influence of RT on renal fibrosis, renal cytokine expression, creatine kinase levels, and muscle mass and strength in CKD rats. A CKD model was obtained by 5/6 nephrectomy (Nx). Fifteen 8-week-old male rats were divided into 3 groups: Sham (control), Nx SED (CKD sedentary) and Nx RT (CKD trained). The RT consisted of ladder climbing at 70% of the animal's maximal carrying capacity for 10 weeks. Muscle strength, creatine kinase levels, renal fibrosis and mRNA interleukin (IL)-4, IL-6 and IL-10 were analyzed after the RT protocol. There was significant improvement in the muscle strength and creatine kinase levels in the Nx RT group. Moreover, renal fibrosis and inflammation were attenuated, with increased IL-4 and IL-10 expression and reduced IL-6 expression in the Nx RT group compared with that in the Nx SED group. No difference in muscle mass was observed among the groups. In conclusion, RT was effective in reducing fibrosis and inflammation, in addition to increasing muscle strength and creatine kinase levels, in rats with CKD, independent of muscle mass. [ABSTRACT FROM AUTHOR]

Proteinuria is a common adverse effect of renal injury in preeclampsia. To explore the effects of AKR1C3 in renal injury due to preeclampsia and to determine an optimal method to prevent proteinuria, glibenclamide treatment was used in unrestrained Wistar rats exposed to N-nitro-L-arginine methyl ester hydrochloride (L-NAME). Successful rat models for preeclampsia were confirmed based on mean arterial pressure, a 24-h protein urine test, and by observing the structure of the kidney by transmission electron microscopy (TEM). Forty Wistar rats were randomly divided into L-NAME-induced preeclampsia (pregnant and L-NAME), treatment (pregnant, L-NAME, and glybenclamide), non-pregnant (L-NAME), and control (pregnant and 0.9% saline) groups. Rats that were 19 days into their pregnancies were then euthanized and their kidneys were collected. After exposure to L-NAME, the mean arterial pressure increased by ~25 mmHg, which was largely prevented by the co-administration of glibenclamide. At 24 h, protein levels in the urine of the L-NAME-induced preeclampsia group were higher than those of the control and treatment groups. AKR1C3 was downregulated in the kidney and podocytes, whereas glibenclamide increased the expression of AKR1C3 . The generation of reactive oxygen species (ROS) detected by ELISA was decreased by the glibenclamide co-administration. Compared with that in the L-NAME-induced preeclampsia group, the expression levels of AKR1C3 protein and mRNA significantly increased in the treatment group ([0.48 ± 0.09] vs.[1.05 ± 0.20];[0.05 ± 0.02] vs.[0.22 ± 0.06]; both P  < 0.05]). Therefore, AKR1C3 expression was decreased in the kidneys of L-NAME-induced preeclampsia rats, and glibenclamide may be useful for the treatment of preeclampsia by regulating the generation of ROS and preventing proteinuria. [ABSTRACT FROM AUTHOR]

Melamine and phthalate, mainly di-(2-ethylhexyl) phthalate (DEHP), are ubiquitously present in the general environment. We investigated whether urine melamine levels can modify the relationship between DEHP exposure and markers of early renal damage in children. A nationwide health survey for Children aged ≤12 years possibly exposed to phthalates were enrolled between August 2012 and January 2013. They were administered questionnaires to collect details regarding past DEHP exposure to phthalate-tainted foodstuffs. Urine samples were measured melamine levels, phthalate metabolites and biomarkers of renal damage, including urine microalbumin/creatinine ratio (ACR), N-acetyl-beta- d -glucosaminidase (NAG), and β2-microglobulin. The study included 224 children who had a median urine melamine level (μg/mmol creatinine) of 1.61 ranging 0.18–47.42. Positive correlations were found between urine melamine levels and urine ACR as well as urine NAG levels (both Spearman correlation coefficients r = 0.24, n = 224, p < .001). The higher the past DEHP exposure or urine melamine levels, the higher the prevalence of microalbuminuria. An interaction effect was also found between urine melamine levels and past DEHP exposure on urine ACR. Melamine levels may further modify the effect of past DEHP exposure on urine ACR in children. [ABSTRACT FROM AUTHOR]

Luteolin (Lut) belongs to the flavonoid family with various beneficial bioactivities. Here, we investigated whether Lut attenuate mercuric chloride (HgCl 2 )-induced renal injury in rat. We found that oral gavage administration of Lut (80 mg/kg) alleviated anemia and renal histology upon HgCl 2 treatment (80 mg/L). Lut also significantly reduced HgCl 2 -induced oxidative stress and inflammatory, presenting as the reduced malondialdehyde (MDA) formation, increased glutathione (GSH) level, and inhibited activation of nuclear factor kappa B (NF-κB). Moreover, Lut protected renal cells from HgCl 2 -induced apoptosis, as assessed by Terminal deoxynucleotidyl transferase dUNT nick end labeling (TUNEL) assay and the protein levels of B-cell lymphoma gene 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), Bcl-2-associated X protein (Bax), and p53. Interestingly, Lut reduced renal mercuric accumulation in rat. Furthermore, Lut increased nuclear translocation of the nuclear factor-erythroid-2-related factor 2 (Nrf2), and subsequent protein expression of the antioxidant enzymes, heme oxygenase-1 (HO-1) and nicotinamide adenine dinucleotide phosphatase: quinone-acceptor 1 (NQO1). Our results suggest that Lut suppress HgCl 2 -induced renal injury via activation of Nrf2 signaling pathway. [ABSTRACT FROM AUTHOR]

To investigate the acute toxicity of Sanghuangporus ethanol extract (SHEE) on ICR mice and the underlying mechanism of anti-hyperuricemic renal injury. ICR mice were given a single gavage of 1250, 2500, and 5000 mg/kg SHEE, and the general behavior, mortality, body weight, dietary, and water intake were evaluated within 14 days to determine the acute toxicity level. The hyperuricemic kidney injury model in ICR mice was induced with potassium oxonate (PO) and adenine, and the mice were subsequently treated with SHEE (125, 250, 500 mg/kg). HE and hexamine silver staining (PASM) were used to observe the pathology of the kidney. Biochemical markers were tested by uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN), xanthine oxidase (XOD), alanine transferase (ALT), and aspartate transaminase (AST) kits. An MTT assay was used to measure the effects of SHEE on the proliferation of HK-2 damaged by UA. Western blotting and RT-PCR were used to determine the expression of Bcl-2 family-related proteins and major UA transporters, including URAT1, GLUT9, OAT1, OAT3, and ABCG2, respectively. Results: Firstly, the acute toxicity study data showed that the median lethal dose (LD 50) of SHEE was above 5000 mg/kg, and its oral administration was nontoxic at 2500 mg/kg and below. In addition, SHEE alleviated HUA and its renal injury in ICR mice. SHEE reduced the contents of UA, Cr, BUN and XOD in blood and the contents of ALT and AST in the liver. Furthermore, SHEE inhibited the expression of URAT1 and GLUT9 and promoted the expression of OAT1, OAT3, and ABCG2. More importantly, SHEE could downregulate the apoptosis level and caspase-3 activity. Conclusions: Overall, an oral dose of SHEE below 2500 mg/kg is safe. SHEE inhibits HUA-induced kidney injury by regulating the UA transporters URAT1, GLUT9, OAT1, OAT3 and ABCG2 and inhibiting HK-2 apoptosis. [Display omitted] • The first report of the acute toxicity of Sanghuangporus in mice. • Sanghuangporus's LD 50 is greater than 5000 mg/kg, suggesting non-toxicity. • Sanghuangporus can alleviate hyperuricemic renal injury. • Sanghuangporus can regulate uric acid transporters. • Sanghuangporus can inhibit HK-2 apoptosis. [ABSTRACT FROM AUTHOR]

The potential protective role of the standardized leaf extract of ginkgo biloba (EGb761) on hypertension with hypercholesterolemia-induced renal injury was investigated in rats. Hypertension was induced by L-N(G)-nitroarginine methyl ester (L-NAME) and hypercholesterolemia was induced by feeding rats with a diet containing 1% cholesterol. In these animals repeated treatment with EGb761 produced a progressive reduction in the systolic, diastolic and mean arterial blood pressure (BP). EGb761 increased the progressive reduction in the systolic, diastolic and mean arterial BP induced by repeated administration of losartan with simvastatin. EGb761 corrected the compromised serum lipid profile and enhanced the effect of losartan with simvastatin on lipid profile. EGb761 protected against hypertension with hypercholesterolemia-induced renal injury as assessed by measurement of serum renal function markers and by histopathological examination. EGb761 enhanced the renoprotective effect of losartan with simvastatin in these rats. Concomitantly, hypertension with hypercholesterolemia-induced elevation of renal tissue malondialdehyde (MDA) and nitrite levels and reduction of intracellular reduced glutathione (GSH) level were inhibited by repeated treatment with EGb761. In addition, hypertension with hypercholesterolemia-induced increases in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels in renal tissues were inhibited by treatment with EGb761. Also, EGb761 inhibited hypertension with hypercholesterolemia-induced decrease in endothelial nitric oxide synthase (eNOS) protein expression and increase in the protein expressions of inducible NO synthase (iNOS), TNF-α, IL-6 and IL-1β in the kidney tissues. Losartan with simvastatin produced similar effects on renal tissues oxidative stress, nitrite and inflammatory markers levels and on protein expressions of eNOS, iNOS, TNF-α, IL-6 and IL-1β. EGb761 enhanced losartan with simvastatin effects. These results indicate that EGb761 has the ability to protect against hypertension with hypercholesterolemia-induced renal injury. The ability of EGb761 to provide this renoprotective effect may positively correlate, besides its antihypertensive and antihypercholesterolemic effects, to its ability to suppress renal oxidative stress, nitrosative stress and inflammation. [ABSTRACT FROM AUTHOR]

Objective Diabetic nephropathy is one of the most devastating complications of diabetes, and growing evidence implicates podocyte dysfunction in disease pathogenesis. The objective of this study was to investigate the contribution of protein tyrosine phosphatase 1B (PTP1B) in podocytes to hyperglycemia-induced renal injury. Methods To determine the in vivo function of PTP1B in podocytes we generated mice with podocyte-specific PTP1B disruption (hereafter termed pod-PTP1B KO). Kidney functions were determined in control and pod-PTP1B KO mice under normoglycemia and high-fat diet (HFD)- and streptozotocin (STZ)-induced hyperglycemia. Results PTP1B expression increased in murine kidneys following HFD and STZ challenges. Under normoglycemia control and pod-PTP1B KO mice exhibited comparable renal functions. However, podocyte PTP1B disruption attenuated hyperglycemia-induced albuminuria and renal injury and preserved glucose control. Also, podocyte PTP1B disruption was accompanied with improved renal insulin signaling and enhanced autophagy with decreased inflammation and fibrosis. Moreover, the beneficial effects of podocyte PTP1B disruption in vivo were recapitulated in E11 murine podocytes with lentiviral-mediated PTP1B knockdown. Reconstitution of PTP1B in knockdown podocytes reversed the enhanced insulin signaling and autophagy suggesting that they were likely a consequence of PTP1B deficiency. Further, pharmacological attenuation of autophagy in PTP1B knockdown podocytes mitigated the protective effects of PTP1B deficiency. Conclusions These findings demonstrate that podocyte PTP1B deficiency attenuates hyperglycemia-induced renal damage and suggest that PTP1B may present a therapeutic target in renal injury. [ABSTRACT FROM AUTHOR]

Background Arsenic (As) contamination is an extremely dangerous global environmental problem as it can enter into the food chain and become bio-accumulated, endangering human health. Chronic As intoxication leads to undesirable toxic effects in various organ systems of the body, especially the kidney. Diallyl trisulfide (DATS) is an organosulfur compound which has been widely known for its uses as antibacterial, antitumorogenic, antioxidant agent and has been also reported to have anti-apoptotic and anti-inflammatory properties. Purpose In the present work, we intend to investigate the protective role of DATS, a garlic organosulfur compound in preventing the As-induced oxidative stress mediated renal injury in rats. Study design The activity of DATS to antagonize As-induced renal oxidative toxicity was analyzed using rats as an in vivo model. Methods We investigated the nephroprotective effect of DATS on As treated rats by performing various serological, biochemical, molecular and histological studies. The activation of Nrf2 was investigated using western blot. Results The data showed that As exposure significantly increased the serum and urine nephritic, oxidative stress, apoptosis and inflammatory markers in the renal tissue of rats. As intoxication also decreased the antioxidant status of the renal tissue along with the disturbances in the membrane bound ATPases. As nephrotoxicity was further confirmed with the altered morphological and ultrastructural changes in the renal tissue. Conversely, the DATS pre-administration effectively recuperate the altered renal variables by As, which has been further supported by the histological and ultrastructural observations. This counteraction was achieved partially via the activation of Nrf2-ARE pathway through the activation of Akt. Conclusion These findings explicate the prospective use of DATS as a promising organosulfur compound against As-induced renal oxidative dysfunction in rats. [ABSTRACT FROM AUTHOR]

The pro-inflammatory cyclooxygenase (COX)-derived prostaglandins and the anti-inflammatory cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) play an important role in the regulation of renal injury. The current study examined whether COX inhibition augments the reno-protective effects of increased EETs levels via inhibiting EETs degradation by soluble epoxide hydrolase (sEH) in diabetic rats. Streptozotocin (50 mg/kg, i.v) was used to induce diabetes in male Sprague Dawley rats. Rats were then divided into 5 groups (n = 6-8); control non diabetic, diabetic, diabetic treated with the sEH inhibitor trans -4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), diabetic treated with the COX inhibitor meloxicam and diabetic treated with meloxicam plus t-AUCB for 2 months. Glomerular albumin permeability and urinary albumin and nephrin excretion levels were significantly elevated in diabetic rats together with decreased glomerular α3 integrin and nephrin expression levels. Inhibition of sEH reduced glomerular albumin permeability, albumin and nephrin excretion levels and restored the decrease in glomerular α3 integrin and nephrin expression in diabetic rats. Meloxicam failed to reduce renal injury or even to synergize the reno-protective effects of sEH inhibition in diabetic rats. Furthermore, inhibition of sEH reduced the elevation in renal collagen deposition and urinary MCP-1 excretion levels together with a reduction in the number of renal TUNEL positive cells in diabetic vs. control rats (P < 0.05). Meloxicam did not reduce renal inflammation or apoptosis in diabetic rats or even exacerbate the anti-inflammatory and anti-apoptotic effects of sEH inhibition. Renal 20-hydroxyeicosatetranoic acid (20-HETE) levels were elevated in diabetic rats and meloxicam further exacerbated this elevation. In conclusion, our study suggests that inhibition of COX failed to provide renal protection or to augment the reno-protective effects of sEH inhibition in diabetic rats, at least in part, via increased inflammatory 20-HETE levels. [ABSTRACT FROM AUTHOR]

As a natural compound extracted from the roots of Cudrania tricuspidata Bureau, Cudratricusxanthone A (CTXA) is known to possess hepatoprotective, anti-inflammatory, and anti-proliferative activities. This study was aimed to clarify the role of CTXA in modulating renal functional damage in a mouse model of sepsis and to elucidate its underlying mechanisms. We examined the renal protective effects of CTXA on cecal ligation and puncture (CLP)-induced renal damage by assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Post-treatment with CTXA resulted in a significant reduction in the deleterious renal functions by CLP, such as elevated BUN, creatinine, and urine protein. Induction of nitric oxide synthase and excessive production of nitric acid by CLP surgery were significantly reduced by post-treatment with CTXA via inhibiting nuclear factor-κB activation. Furthermore, the plasma levels of interleukin-6 and tumor necrosis factor-α were suppressed by CTXA post-treatment. Concurrently, CTXA treatment potently suppressed the CLP-induced septic lethality, rise of lipid peroxidation and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney. The present results suggested that CTXA could protect against sepsis-triggered renal injury in mice. [ABSTRACT FROM AUTHOR]

Aims We examined the roles of xanthine oxidoreductase (XOR) in renal ischemia reperfusion (IR) injury. Main methods XOR +/+ and XOR +/− mice were subjected to 24-h reperfusion after a 45-min bilateral renal artery occlusion or sham operation. We evaluated the renal damage based on the concentrations of blood urea nitrogen (BUN) and serum creatinine (Cr), and histological changes were detected by PAS staining. Xanthine dehydrogenase, oxidase (XO) and XOR activities, amounts of blood and urine 8-OHdG, and expressions of TNF-α and MCP-1 mRNA were examined. F4/80 and nitrotyrosine-positive cells were assessed by immunohistochemical staining. Key findings The BUN and Cr concentrations in the XOR +/+IR mice were increased significantly compared to those in XOR +/−IR and allopurinol-treated XOR +/+IR mice. XO and XOR activity, which were increased in IR mice, were reduced in the allopurinol-treated XOR +/+IR and XOR +/−IR mice compared to the XOR +/+IR mice. The concentrations of blood and urine 8-OHdG, and the expressions of MCP-1 and TNF-α mRNA were increased significantly in the XOR +/+IR mice compared to those in the XOR +/−IR mice. The histological analysis revealed that the XOR +/−IR and allopurinol-treated XOR +/+IR mice showed less tubular injury than the XOR +/+IR mice in the cortex regions, with the reduction of inflammation and oxidative stress assessed by the immunohistological staining for F4/80 and nitrotyrosine. Significance Both the disruption of XOR gene in XOR +/− mice and the reduction of XOR activity in allopurinol-treated XOR +/+IR mice attenuated renal tissue injury in this IR model. Reduced XOR activity during renal IR could be a beneficial treatment target. [ABSTRACT FROM AUTHOR]