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Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been reported to have effects beyond lowering blood glucose levels, with certain SGLT2i expanding their indications to chronic kidney disease and chronic heart failure. We focused on the hepatoprotective and renoprotective effects of six SGLT2i and assessed whether the effects were unique to each drug or common class effects, in addition to whether the renal and hepatoprotective effects vary based on renal and hepatic status. Methods: Patients with diabetes (ipragliflozin: 837, empagliflozin: 850, canagliflozin: 922, dapagliflozin: 590, tofogliflozin: 288, and luseogliflozin: 193) who initiated SGLT2i treatment and were monitored for one year were included. The propensity score (PS) was calculated using patient backgrounds (age, sex, height, weight, body mass index [BMI], disease duration, concomitant diabetes medications, underlying conditions, glycated hemoglobin [HbA1c], estimated glomerular filtration rate [eGFR], aspartate aminotransferase [AST], alanine aminotransferase [ALT], high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglyceride [TG] levels) as covariates. Additionally, the inverse probability of treatment weighting (IPTW) approach was used to compare liver and renal function test values. Results: Pre- and 12-month post-treatment comparisons demonstrated a significant reduction in hepatic function (AST and ALT) and an increase in renal function (eCcr and eGFR) for all SGLT2i. Comparison of differences between pre- and 12-month post-treatment using the IPTW approach demonstrated no significant differences in AST, ALT, and eGFR levels between SGLT2i. At 12 months post-treatment, 67 patients were classified as having a more severe CKD than those at pre-treatment, representing only 1.8% of all patients (67/3,680). Similarly, 107 patients with AST and 147 patients with ALT were classified as having progressed to a more severe grade than at pre-treatment, representing only 2.9 and 4.0%, respectively. Conclusions: Renoprotective and hepatoprotective effects are class effects of SGLT2i, and their effects are thought to be independent of kidney or liver status. [ABSTRACT FROM AUTHOR]

Abstract Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been reported to have effects beyond lowering blood glucose levels, with certain SGLT2i expanding their indications to chronic kidney disease and chronic heart failure. We focused on the hepatoprotective and renoprotective effects of six SGLT2i and assessed whether the effects were unique to each drug or common class effects, in addition to whether the renal and hepatoprotective effects vary based on renal and hepatic status. Methods Patients with diabetes (ipragliflozin: 837, empagliflozin: 850, canagliflozin: 922, dapagliflozin: 590, tofogliflozin: 288, and luseogliflozin: 193) who initiated SGLT2i treatment and were monitored for one year were included. The propensity score (PS) was calculated using patient backgrounds (age, sex, height, weight, body mass index [BMI], disease duration, concomitant diabetes medications, underlying conditions, glycated hemoglobin [HbA1c], estimated glomerular filtration rate [eGFR], aspartate aminotransferase [AST], alanine aminotransferase [ALT], high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglyceride [TG] levels) as covariates. Additionally, the inverse probability of treatment weighting (IPTW) approach was used to compare liver and renal function test values. Results Pre- and 12-month post-treatment comparisons demonstrated a significant reduction in hepatic function (AST and ALT) and an increase in renal function (eCcr and eGFR) for all SGLT2i. Comparison of differences between pre- and 12-month post-treatment using the IPTW approach demonstrated no significant differences in AST, ALT, and eGFR levels between SGLT2i. At 12 months post-treatment, 67 patients were classified as having a more severe CKD than those at pre-treatment, representing only 1.8% of all patients (67/3,680). Similarly, 107 patients with AST and 147 patients with ALT were classified as having progressed to a more severe grade than at pre-treatment, representing only 2.9 and 4.0%, respectively. Conclusions Renoprotective and hepatoprotective effects are class effects of SGLT2i, and their effects are thought to be independent of kidney or liver status.

Glucagon-like Peptide-1 (GLP-1) receptor agonists (GLP-1RAs) emerged as a primary treatment for type-2 diabetes mellitus (T2DM), however, their multifaceted effects on various target organs beyond glycemic control opened a new era of treatment. We conducted a comprehensive literature search using databases including Scopus, Google Scholar, PubMed, and the Cochrane Library to identify clinical, in-vivo, and in-vitro studies focusing on the diverse effects of GLP-1 receptor agonists. Eligible studies were selected based on their relevance to the varied roles of GLP-1RAs in T2DM management and their impact on other physiological functions. Numerous studies have reported the efficacy of GLP-1RAs in improving outcomes in T2DM, with demonstrated benefits including glucose-dependent insulinotropic actions, modulation of insulin signaling pathways, and reductions in glycemic excursions. Additionally, GLP-1 receptors are expressed in various tissues and organs, suggesting their widespread physiological functions beyond glycemic control potentially include neuroprotective, anti-inflammatory, cardioprotective, and metabolic benefits. However, further scientific studies are still underway to maximize the benefits of GLP-1RAs and to discover additional roles in improving health benefits. This article sought to review not only the actions of GLP1RAs in the treatment of T2DM but also explore its effects on potential targets in other disorders. [ABSTRACT FROM AUTHOR]

Background: Diabetes Mellitus (DM) is a long-term condition marked by high blood glucose levels caused by insulin resistance which will lead to complications of other diseases such as dyslipidemia which also affects the health of the liver and kidneys. Butterfly Pea Flower (Clitorea ternatea L.) has phenolic and flavonoid compounds which have the potential as herbal medicines for antidiabetics. Aim: The purpose of this study is to examine the potential of Butterfly Pea Flower Extract (BPE) as an antidiabetic, anti-dyslipidemia, and renoprotection. Methods: In vivo test was performed on Sprague Dawley rats (Rattus norvegicus L.) induced by Streptozotocin-Nicotinamide and High Fat Diet-Propylthiouracil as models of DM and dyslipidemia, and BPE was administered orally (200, 400, and 800 mg /kg BW) for 28 days. GSH-Px, GST, TNF-α, NF-kB, ALP, liver albumin levels, serum BUN, SCr, and serum UA, were measured by ELISA and colorimetry methods. Results: Treatment of BPE 800 mg/kg BW increase levels of GSH-Px, GST, albumin, and serum protein. BPE decreases TNF-α, NF-kB, and ALP. BPE also decreases BUN, serum CR, and serum UA. Conclusion: BPE has the potential to be used as a drug alternative for the treatment of diabetes mellitus and dyslipidemia as well as a hepatoprotective and renoprotective agent. [Open Vet J 2024; 14(5.000): 1135-1145]

Background: To compare kidney blood flow and kidney function tests in infants with hypoxic ischemic encephalopathy (HIE), and the effects of therapeutic hypothermia (TH) during the first 7 days of life. Methods: Fifty-nine infants with HIE were prospectively evaluated. Infants with moderate-severe HIE who required TH were classified as group 1 (n = 36), infants with mild HIE were classified as group 2 (n = 23), and healthy infants were classified as group 3 (n = 60). Kidney function tests were evaluated on the sixth hour, third and seventh days of life in Group 1 and Group 2, and on the sixth hour and third day of life in group 3. Renal artery (RA) Doppler ultrasonography (dUS) was performed in all infants on the first, third, and seventh days of life. Results: Systolic and end diastolic blood flow in RA tended to increase and RA resistive index (RI) tended to decrease with time in group 1 (p = 0.0001). While end diastolic blood flow rates in RA on the third day were similar in patients with severe HIE and mild HIE, it was lower in patients with mild-moderate-severe HIE than healthy newborns. On the seventh day, all three groups had similar values (p > 0.05). Serum blood urea nitrogen (BUN), creatinine, uric acid, and cystatin C levels gradually decreased and glomerular filtration rate (GFR) gradually increased during TH in group 1 (p = 0.0001). Serum creatinine levels gradually decreased while GFR gradually increased during the study period in group 2. Conclusions: Therapeutic hypothermia seems to help restore renal blood flow and kidney functions during the neonatal adaptive period with its neuroprotective properties. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a challenging public health issue, particularly in poor and developing countries. Rifampicin (RIF) is one of the most common first-line anti-TB drugs but it is known for its adverse effects on the hepato-renal system. The present study investigated the efficacy of morin hydrate (MH) in protecting hepato-renal damage inflicted by RIF in rats. RIF (50 mg/kg), and a combination of RIF (50 mg/kg) and MH (50 mg/kg) were administered orally for 4 weeks in rats. Silymarin (50 mg/kg) was used as a positive control. Increased levels of serological parameters such as AST, ALT, ALP, LDH, GGT, bilirubin, triglyceride, total cholesterol, urea, uric acid, creatinine, TNF-α, IFN-γ, IL-6 along with the decreased level of IL-10, total protein and albumin were used as markers of hepatic and renal injury. Oxidative damage in the tissues was measured by the increase in lipid peroxidation and decline in GSH, SOD and catalase activities. Histopathology of liver slices was used to study hepatic architecture. Four-week RIF treatment produced altered serological parameters with an increase in pro-inflammatory cytokines in serum suggesting hepatotoxicity and nephrotoxicity. The antioxidant status of the liver and kidney (increased lipid peroxidation and decline in GSH, SOD and catalase) was compromised. Cellular damage and necrosis were observed in liver slices. MH supplementation with RIF improved hepato-renal functions by restoring the serum and tissue markers towards normal values. Histological observations authenticated the results. MH supplementation also reduced the production of pro-inflammatory cytokines. Thus, the results revealed that MH provides protection against RIF-induced hepato-renal injury. [ABSTRACT FROM AUTHOR]

Hippocratea africana root used locally in the treatment of poisoning was investigated to confirm its antidotal potential in rats. The root extract (200-600 mg/kg) and fractions; dichloromethane (DCM) and aqueous, 400 mg/kg) were evaluated for nephroprotective activity against doxorubicin-induced kidney injury in rats. Kidney function parameters, kidney oxidative stress markers and kidney histology were used to assess the kidney protective effect of the extract. The root extract and fractions (200-600 mg/kg) significantly (p

OBJECTIVE: Even though oxidative and inflammatory bursts are a big part of renal reperfusion injury (RI/R), Pistia stratiotes (PS) has been used for a long time to stop these overreactions. People have said that it can drop both blood sugar and cholesterol. Hence, the goal of this study was to show how PS changed kidney reperfusion damage in both diabetic and normal rats. MATERIALS AND METHODS: In the study, 30 min of renal ischemia (RI) was followed by 1 h of recovery for each rat. Before the test, PS (100 mg/kg p. o.) was given to the animals for 7 days. Then, using the mixture from the separated kidney tissues, the antioxidant, inflammation, and histopathological effects were determined. RESULTS: When compared to RI/R, diabetic rats given PS had lower blood sugar, aspartate aminotransferase, blood urea nitrogen, and creatinine, myeloperoxidase, C-reactive protein, and tumor necrosis factor-alpha levels in their urine. CONCLUSION: PS potentially worked in hyperglycemic rats protecting them against RI/R. It is possible that PS's ability to protect the kidneys of the test rats is due to its ability to fight free radicals, lower blood sugar, and stop inflammation. [ABSTRACT FROM AUTHOR]

Cisplatin is an effective chemotherapeutic drug widely used for the treatment of various solid tumors; however, its clinical use and efficacy are limited by its inherent nephrotoxicity. The pathogenesis of cisplatin-induced nephrotoxicity is complex and has not been fully elucidated. Cellular uptake and transport, DNA damage, apoptosis, oxidative stress, inflammatory response, and autophagy are involved in the development of cisplatin-induced nephrotoxicity. Currently, despite some deficiencies, hydration regimens remain the major protective measures against cisplatin-induced nephrotoxicity. Therefore, effective drugs must be explored and developed to prevent and treat cisplatin-induced kidney injury. In recent years, many natural compounds with high efficiency and low toxicity have been identified for the treatment of cisplatin-induced nephrotoxicity, including quercetin, saikosaponin D, berberine, resveratrol, and curcumin. These natural agents have multiple targets, multiple effects, and low drug resistance; therefore, they can be safely used as a supplementary regimen or combination therapy for cisplatin-induced nephrotoxicity. This review aimed to comprehensively describe the molecular mechanisms underlying cisplatin-induced nephrotoxicity and summarize natural kidney-protecting compounds to provide new ideas for the development of better therapeutic agents. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is one of the major side effects of cisplatin, a remarkable anticancer agent. Therefore, there is a growing need to find an agent that could mitigate cisplatin-induced nephrotoxicity. Betulinic acid (BA) is a natural compound isolated from Silene succulenta Forssk for the first time, with miraculous biological activities and no reports of its effect on the nephrotoxicity induced by cisplatin. Mice received BA orally with doses of 30 and 50 mg/kg before the intraperitoneal injection of cisplatin. Betulinic acid was found to decrease serum levels of creatinine and tissue levels of NGAL and kidney injury molecule (KIM-1) and improve the histological changes in the kidney. In addition, BA decreased the oxidative stress marker malondialdehyde (MDA), increased superoxide dismutase (SOD) antioxidative activity and suppressed the intensity of IL-1B and NFкB immuno-staining. Interestingly, betulinic acid enhanced autophagy by increasing beclin 1, ATG5, and LC3II and decreasing p62 expressions. Thus, our findings suggest betulinic acid as a potential agent that may protect from acute kidney injury by targeting inflammation, oxidative stress, and autophagy processes. Novel drugs are needed to combat the spreading of multidrug resistance between pathogenic bacteria, especially uropathogenic isolates. So, we elucidated the antibacterial properties of BA on Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. Betulinic acid had minimum inhibitory concentration values (128 to 512 µg/mL). In addition, it adversely affected the membrane integrity of the tested isolates. Accordingly, betulinic acid should be clinically investigated in the future for urinary tract diseases. [ABSTRACT FROM AUTHOR]

The spreading Hogweed or Boerhaavia diffusa L. (BD) is a potent herbal medicine with diverse pharmacological activities. In Asia and Africa, it is used in different Ayurvedic medicines as a rejuvenator or "Rasayan" for its excellent antiaging and antioxidant properties. This review is intended to provide an extensive study on different phytochemicals present in BD and their relevant pharmacological activities to support its ethno medicinal uses. Further, this may help in exploring the undiscovered active constituents of BD, responsible for its diverse pharmacological uses. The data from different published research and review articles, confined to phytochemistry and pharmacological activities of different parts of BD, were extracted by using specific keywords from different scientific databases like Google, Science Direct, PubMed, etc. The whole plant (root, stem, leaf, flower and fruits) is rich in different bioactive phytocompounds. Till date, many of them were isolated from the roots and other parts of BD, but the most important secondary metabolites are phenolics, rotenoids, flavonoids, isoflavonoids, alkaloids, steroids, anthracenes and lignans. The crude extracts and the purified compounds were reported to have promising activities like antimicrobial, antioxidant, anticancer, anti-inflammatory, immunomodulatory, antidiabetic, hepatoprotective, renoprotective, cardio protective, antifertility etc. As the reports on molecular mechanisms of specific interaction between isolated compounds and microbial effector proteins/toxins or their interference with molecular pathogenesis are limited, further investigation can be carried out to understand the prophylactic and therapeutic role of these phytomolecules in different diseases at a molecular level using appropriate experimental models. [ABSTRACT FROM AUTHOR]

Copyright of Modern Food Science & Technology is the property of Editorial Office of Modern Food Science & Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Context Gentamicin (GM) is an aminoglycoside antibiotic which is commonly used against Gram-negative bacterial infection; however, serious complications including nephrotoxicity could limit its clinical use. Objective The present study examined the protective effects of curcumin (CUR) on endoplasmic reticulum (ER) stress-mediated apoptosis through its antioxidative property in GM-induced nephrotoxicity in rats. Materials and methods Male Sprague-Dawley rats (n = 3) were divided into six groups to receive normal saline (control), GM (100 mg/kg/day), co-treatment with GM and CUR (100, 200 and 300 mg/kg/day) and CUR (200 mg/kg/day) alone for 15 days by gavage feeding. Then, the renal function, kidney injury as well as oxidative stress, antioxidative markers and ER stress-mediated apoptosis were evaluated. Results Pre-treatment of CUR rescued the nephrotoxicity in GM-treated rats. Several nephrotoxicity hallmarks were reversed in the CUR-pre-treatment group. At the dose of 200 mg/kg/day, it could significantly lower serum creatinine (from 0.95 to 0.50 mg/dL), blood urea nitrogen (from 35.00 to 23.50 mg/dL) and augmented creatinine clearance (from 0.83 to 1.71 mL/min). The normalized expression of oxidative stress marker, malondialdehyde was decreased (from 13.00 to 5.98) in line with the increase of antioxidant molecules including superoxide dismutase (from 5.59 to 14.24) and glutathione (from 5.22 to 12.53). Furthermore, the renal ER stress and apoptotic protein biomarkers were lowered in CUR treatment. Discussion and conclusions Our findings pave the way for the application of CUR as a supplement in the prevention of nephrotoxicity and other kidney diseases in the future.

Context Chitosan is a biocompatible polysaccharide that has been widely exploited in biomedical and drug delivery applications.Objective This study explores the renoprotective effect of chitosan nanoparticles in vivo in rats.Materials and methods Chitosan nanoparticles were prepared via ionotropic gelation method, and several in vitro characterizations were performed, including measurements of particle size, zeta potential, polydispersity index, Fourier transform-infrared spectroscopy, differential scanning calorimetry, and transmission electron microscopy (TEM) imaging. Wistar rats were divided randomly into four groups; negative control, CCl4-induced nephrotoxicity (untreated), and two groups receiving CCl4 + chitosan NPs (10 and 20 mg/kg) orally for 2 weeks. The renoprotective effect was assessed by measuring oxidative, apoptotic, and inflammatory biomarkers, and via histopathological and immunohistochemical examinations for the visualization of NF-κB and COX-2 in renal tissues.Results Monodisperse spherical nanosized (56 nm) particles were successfully prepared as evidenced by dynamic light scattering and TEM. Oral administration of chitosan nanoparticles (10 and 20 mg/kg) concurrently with CCl4 for 2 weeks resulted in 13.6% and 21.5% reduction in serum creatinine and increase in the level of depleted reduced glutathione (23.1% and 31.8%), respectively, when compared with the positive control group. Chitosan nanoparticles (20 mg/kg) revealed a significant (p ˂ 0.05) decrease in malondialdehyde levels (30.6%), tumour necrosis factor-α (33.6%), interleukin-1β (31.1%), and caspase-3 (36.6%).Conclusions Chitosan nanoparticles afforded significant protection and amelioration against CCl4-induced nephrotoxicity. Thus, chitosan nanoparticles could afford a potential nanotherapeutic system for the management of nephrotoxicity which allows for broadening their role in biomedical delivery applications.

Sodium-glucose co-transporter 2 inhibitors (SGLT2is) are recommended as the next step therapy for the management of diabetes mellitus. The large clinical trials of SGLT2is demonstrated benefits on various renal endpoints. We conducted this meta-analysis of large trials on cardiovascular and renal safety trials to explore the renoprotective effect of this group of drugs. PubMed, Cochrane CENTRAL, and EMBASE databases were searched with specific keywords till January 19, 2021. Randomized trials of SGLT2is that evaluated the cardiovascular or renal composite outcome as a primary outcome measure were eligible. Random-effects model was used to calculate the overall risk ratios. The search yielded 716 studies and 10 studies were included. The SGLT2is reduced the risk of composite renal outcome (risk ratio [RR] = 0.64, 95% confidence interval [CI] = 0.58-0.72), decline in estimated glomerular filtration rate (eGFR) (RR = 0.62, 95% CI = 0.50-0.77), doubling of serum creatinine (RR = 0.67, 95% CI = 0.56-0.81), dialysis or renal replacement therapy (RR = 0.71, 95% CI = 0.59-0.86), sustained eGFR of <15 ml per min per 1.73 m2 for at least 30 days or more (RR = 0.66, 95% CI = 0.55-0.81), end-stage renal disease (RR = 0.70, 95% CI = 0.56-0.87), and acute kidney injury (RR = 0.79, 95% CI = 0.71-0.89). This analysis establishes the renoprotective effect of SGLT2is. This benefit is noted in patients who had eGFR of more or <60 ml per min per 1.73 m2. This benefit was uniform across all the SGLT2 inhibitors except ertugliflozin and sotagliflozin. [ABSTRACT FROM AUTHOR]

Abstract Aim The aim of this study was to investigate the renoprotective effects of exosomes derived from rat bone marrow mesenchymal stem cells (rBMSCs) in a rat model of 5/6 nephrectomy (Nx)-induced chronic kidney disease (CKD). Methods A rat model of 5/6 Nx-induced CKD was established using conventional method. rBMSC-derived exosomes were isolated using ultracentrifugation and characterized. The exosomes were injected into 5/6 Nx rats through the caudal vein. After 12 weeks, 24 h proteinuria, serum creatinine (SCr), and blood urea nitrogen (BUN) levels were evaluated, and renal pathology was analyzed by H&E and Masson staining, and transmission electron microscopy. The expression of klotho was analyzed and the activity of the klotho promoter was evaluated using a luciferase reporter assay. Results The isolated exosomes showed typical morphological features. Exosomes transplantation reduced 24 h urinary protein excretion, and SCr and BUN levels in 5/6 Nx-induced CKD rats. Furthermore, renal pathology was improved in the exosome-treated 5/6 Nx rats. Mechanistically, the exosomes significantly upregulated the activity of klotho promoter and its expression. Conclusions Transplantation of rBMSC-derived exosomes may protect against kidney injury, probably by regulating klotho activity and expression. Our results provide a theoretical basis for the application of rBMSC-derived exosomes in CKD therapy.

Copyright of Revista Habanera de Ciencias Médicas is the property of Universidad de Ciencias Medicas de La Habana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cadmium (Cd), a non-redox metal, has been described as an environmental toxicant that poses a great threat to human health. Therefore, this study aimed to appraise the mitigating potential of the aqueous extract of Bridelia ferruginea (Bf) stem bark against hepato-renal toxicity in Cd-exposed Wistar rats. Thirty (30) adult male Wistar rats (weight 150–200 g) were randomly grouped into five (5) groups of six (6) rats each (n = 6), and experimental rats received a single treatment of cadmium chloride (CdCl2; 30 mg/kg body weight (bw)). Cd-exposed rats were administered 50, 100, and 200 mg/kg bw aqueous extract of Bf stem bark for 14 days. Cd exposure caused hepato-renal toxicity in the untreated control as revealed by a significant (p < 0.05) increase in the serum liver function markers (i.e., AST, ALT, and ALP) as well as a marked (p < 0.05) decrease in hepatic antioxidant enzymes. A similar effect was also noticed in the renal function biomarkers (i.e., creatinine and urea) and its antioxidant enzymes. However, Cd-exposed groups–administered aqueous extract of Bf stem bark revealed a significant (p < 0.05) decrease in serum activities of AST, ALP, and ALT, as well as a significant (p > 0.05) difference in TP level compared to Cd-induced hepato-renal toxicity untreated and normal control. Similarly, hepatic and renal antioxidant parameters (SOD, CAT, and GSH), TP, serum lipid profile, urea, and creatinine were significantly (p < 0.05) improved among the groups-administered aqueous extract of Bf stem bark compared to Cd-induced hepato-renal toxicity untreated and normal control. The renal and hepatic Cd concentrations of groups administered aqueous extract of Bf stem bark significant (p < 0.05) decrease compared to Cd-induced hepato-renal toxicity untreated and normal control. Likewise, histological examinations of kidney and liver tissues of the groups administered aqueous extract of Bf stem bark revealed restoration of normal architecture. Therefore, aqueous extract of Bf stem bark could be suggested to be hepatoprotective and renoprotective in Cd toxicity. [ABSTRACT FROM AUTHOR]

Context: Chitosan is a biocompatible polysaccharide that has been widely exploited in biomedical and drug delivery applications. Objective: This study explores the renoprotective effect of chitosan nanoparticles in vivo in rats. Materials and methods: Chitosan nanoparticles were prepared via ionotropic gelation method, and several in vitro characterizations were performed, including measurements of particle size, zeta potential, polydispersity index, Fourier transform-infrared spectroscopy, differential scanning calorimetry, and transmission electron microscopy (TEM) imaging. Wistar rats were divided randomly into four groups; negative control, CCl4-induced nephrotoxicity (untreated), and two groups receiving CCl4 þ chitosan NPs (10 and 20mg/kg) orally for 2 weeks. The renoprotective effect was assessed by measuring oxidative, apoptotic, and inflammatory biomarkers, and via histopathological and immunohistochemical examinations for the visualization of NF-jB and COX-2 in renal tissues. Results: Monodisperse spherical nanosized (56 nm) particles were successfully prepared as evidenced by dynamic light scattering and TEM. Oral administration of chitosan nanoparticles (10 and 20mg/kg) concurrently with CCl4 for 2 weeks resulted in 13.6% and 21.5% reduction in serum creatinine and increase in the level of depleted reduced glutathione (23.1% and 31.8%), respectively, when compared with the positive control group. Chitosan nanoparticles (20mg/kg) revealed a significant (p 0.05) decrease in malondialdehyde levels (30.6%), tumour necrosis factor-a (33.6%), interleukin-1b (31.1%), and caspase-3 (36.6%). Conclusions: Chitosan nanoparticles afforded significant protection and amelioration against CCl4- induced nephrotoxicity. Thus, chitosan nanoparticles could afford a potential nanotherapeutic system for the management of nephrotoxicity which allows for broadening their role in biomedical delivery applications. [ABSTRACT FROM AUTHOR]

Context: Gentamicin (GM) is an aminoglycoside antibiotic which is commonly used against Gram-negative bacterial infection; however, serious complications including nephrotoxicity could limit its clinical use. Objective: The present study examined the protective effects of curcumin (CUR) on endoplasmic reticulum (ER) stress-mediated apoptosis through its antioxidative property in GM-induced nephrotoxicity in rats. Materials and methods: Male Sprague-Dawley rats (n=3) were divided into six groups to receive normal saline (control), GM (100 mg/kg/day), co-treatment with GM and CUR (100, 200 and 300mg/kg/day) and CUR (200mg/kg/day) alone for 15 days by gavage feeding. Then, the renal function, kidney injury as well as oxidative stress, antioxidative markers and ER stress-mediated apoptosis were evaluated. Results: Pre-treatment of CUR rescued the nephrotoxicity in GM-treated rats. Several nephrotoxicity hallmarks were reversed in the CUR-pre-treatment group. At the dose of 200 mg/kg/day, it could significantly lower serum creatinine (from 0.95 to 0.50mg/dL), blood urea nitrogen (from 35.00 to 23.50mg/dL) and augmented creatinine clearance (from 0.83 to 1.71 mL/min). The normalized expression of oxidative stress marker, malondialdehyde was decreased (from 13.00 to 5.98) in line with the increase of antioxidant molecules including superoxide dismutase (from 5.59 to 14.24) and glutathione (from 5.22 to 12.53). Furthermore, the renal ER stress and apoptotic protein biomarkers were lowered in CUR treatment. Discussion and conclusions: Our findings pave the way for the application of CUR as a supplement in the prevention of nephrotoxicity and other kidney diseases in the future. [ABSTRACT FROM AUTHOR]

The current study conducted a critical review on available clinical evidence for topiroxostat, indicated for managing hyperuricemia in patients with or without gout. Relevant observational studies related to hyperuricemia and topiroxostat published between 2014 and 2022 were retrieved from various electronic databases based on the inclusion and exclusion criteria and using different combinations of MeSH terms. The systematic search yielded 2094 articles from various databases. Based on the inclusion and exclusion criteria, 16 articles were selected for systematic review. The review considered 16 studies on serum urate-lowering efficacy of topiroxostat and 6 studies that had evaluated the efficacy of the drug in hyperuricemia patients with chronic kidney disease. Four studies that evaluated hyperuricemia patients with cardiovascular risk and 10 studies that had evaluated adverse drug reactions linked to topiroxostat use were also considered. The literature findings validated the safety, efficacy, renoprotective effects, and reduced adverse events conferred by topiroxostat. The most common adverse event noted was gouty arthritis of mild to moderate in severity. The advantages of the drug when compared to the currently available xanthine oxidoreductase inhibitors include unique dual mechanism of action, cardiac safety, and renal protection. [ABSTRACT FROM AUTHOR]

The current study conducted a critical review on available clinical evidence for topiroxostat, indicated for managing hyperuricemia in patients with or without gout. Relevant observational studies related to hyperuricemia and topiroxostat published between 2014 and 2022 were retrieved from various electronic databases based on the inclusion and exclusion criteria and using different combinations of MeSH terms. The systematic search yielded 2094 articles from various databases. Based on the inclusion and exclusion criteria, 16 articles were selected for systematic review. The review considered 16 studies on serum urate-lowering efficacy of topiroxostat and 6 studies that had evaluated the efficacy of the drug in hyperuricemia patients with chronic kidney disease. Four studies that evaluated hyperuricemia patients with cardiovascular risk and 10 studies that had evaluated adverse drug reactions linked to topiroxostat use were also considered. The literature findings validated the safety, efficacy, renoprotective effects, and reduced adverse events conferred by topiroxostat. The most common adverse event noted was gouty arthritis of mild to moderate in severity. The advantages of the drug when compared to the currently available xanthine oxidoreductase inhibitors include unique dual mechanism of action, cardiac safety, and renal protection.

In recent years, the application of phytochemicals to prevent or treat diseases has received greater attention. These phytochemicals have little or no toxicity against healthy tissues and are thus considered as ideal compounds. An impressive number of modern drugs are obtained from natural sources based on their traditional value. D‐Pinitol is a natural compound that is derived from soy and soy products. It is a potentially active molecule that belongs to the class of inositols. D‐pinitol has been pharmacologically evaluated for its potent antioxidant, anti‐diabetic, anti‐inflammatory, anti‐cancer, hepatoprotective, cardioprotective, renoprotective, neuroprotective, immunosuppressive, and anti‐osteoporotic efficacies. This review is an attempt to validate the plausible pharmacological effects of D‐pinitol using various in vivo and in vitro studies. Practical implications: The consumption of plant‐based products has been significantly increased all over the world. The active phytochemicals that are found in plants are stated to have numerous health promoting functions for the treatment of diabetes, cancer, inflammation, cardiac diseases, liver dysfunction, and many other. D‐Pinitol is abundantly present in soybeans that possess notable therapeutic activities. Understanding the effects of D‐Pinitol would potentially help in applying this compound in clinical research for the treatment of different disorders. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is one of the major side effects of cisplatin, a remarkable anticancer agent. Therefore, there is a growing need to find an agent that could mitigate cisplatin-induced nephrotoxicity. Betulinic acid (BA) is a natural compound isolated from Silene succulenta Forssk for the first time, with miraculous biological activities and no reports of its effect on the nephrotoxicity induced by cisplatin. Mice received BA orally with doses of 30 and 50 mg/kg before the intraperitoneal injection of cisplatin. Betulinic acid was found to decrease serum levels of creatinine and tissue levels of NGAL and kidney injury molecule (KIM-1) and improve the histological changes in the kidney. In addition, BA decreased the oxidative stress marker malondialdehyde (MDA), increased superoxide dismutase (SOD) antioxidative activity and suppressed the intensity of IL-1B and NFкB immuno-staining. Interestingly, betulinic acid enhanced autophagy by increasing beclin 1, ATG5, and LC3II and decreasing p62 expressions. Thus, our findings suggest betulinic acid as a potential agent that may protect from acute kidney injury by targeting inflammation, oxidative stress, and autophagy processes. Novel drugs are needed to combat the spreading of multidrug resistance between pathogenic bacteria, especially uropathogenic isolates. So, we elucidated the antibacterial properties of BA on Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. Betulinic acid had minimum inhibitory concentration values (128 to 512 µg/mL). In addition, it adversely affected the membrane integrity of the tested isolates. Accordingly, betulinic acid should be clinically investigated in the future for urinary tract diseases.

Renoprotectors are highly demanded due to environmental nephrotoxic factors. P. longifolia leaves extract alleviating effect was assessed in nephritic-induced rats by whole body shot dose of γ-radiation. Many biomarkers were detected using several assays. Renohistopathological examinations were performed. Moreover, the extract phytoconstituents were identified using spectroscopic analysis. In-vitro anti-inflammatory activity of some compounds was examined using histamine release assay. Post-irradiation treatment with the extract significantly ameliorated all elevated biomarker levels. Creatinine and urea were adjusted, TGF-β/Smad signaling was suppressed causing down-regulation to microRNA-21. Nitric oxide, reactive oxygen species, glutathione and kidney injury molecule-1 were normalized in comparison with the γ-irradiated group. The renohistopathological analysis was consistent with the biochemical study. Phytochemical analysis resulted in the isolation of two diterpenoids (γ-methoxybutenolide clerodane diterpene and 16(R/S)-hydroxycleroda-3,13-dien-16,15-olide-2-one), aporphine alkaloid (anonaine) and flavonol (kaempferol-3-O-rutinoside). The latter two showed moderate anti-histaminic activities. Our results indicated that P. longifolia reduced oxidative stress and nephropathy in rats due to its anti-inflammatory principles. [ABSTRACT FROM AUTHOR]

In the present study, we chemically characterised the aqueous leaf extract of Limoniastrum guyonianum by HPLC-TOF/MS and evaluated its effects on fructose-induced metabolic syndrome (MetS) in Wistar rats. MetS groups were given (10% w/v) fructose solution to drink ad libitum for 9 weeks, whereas, normal animals received ordinary water. LG extract was administrated to treated groups by gavage for the last 6 weeks of the experimental period. Fructose feeding as a liquid solution increased body weight, reduced insulin sensitivity, raised blood glucose level and provoked atherogenic dyslipidemia associated with renal oxidative stress and structural damage. Treating MetS rats with LG extract at doses of 100, 200 and 300 mg/kg b.w./day considerably ameliorated the fructose-induced alterations. From this study, it was concluded that aqueous leaf extract of L. guyonianum possesses hypoglycaemic, hypolipidemic, antioxidant and renoprotective abilities against fructose-induced metabolic syndrome in rats. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the renoprotective effects of exosomes derived from rat bone marrow mesenchymal stem cells (rBMSCs) in a rat model of 5/6 nephrectomy (Nx)-induced chronic kidney disease (CKD). Methods: A rat model of 5/6 Nx-induced CKD was established using conventional method. rBMSC-derived exosomes were isolated using ultracentrifugation and characterized. The exosomes were injected into 5/6 Nx rats through the caudal vein. After 12 weeks, 24 h proteinuria, serum creatinine (SCr), and blood urea nitrogen (BUN) levels were evaluated, and renal pathology was analyzed by H&E and Masson staining, and transmission electron microscopy. The expression of klotho was analyzed and the activity of the klotho promoter was evaluated using a luciferase reporter assay. Results: The isolated exosomes showed typical morphological features. Exosomes transplantation reduced 24 h urinary protein excretion, and SCr and BUN levels in 5/6 Nx-induced CKD rats. Furthermore, renal pathology was improved in the exosome-treated 5/6 Nx rats. Mechanistically, the exosomes significantly upregulated the activity of klotho promoter and its expression. Conclusions: Transplantation of rBMSC-derived exosomes may protect against kidney injury, probably by regulating klotho activity and expression. Our results provide a theoretical basis for the application of rBMSC-derived exosomes in CKD therapy. [ABSTRACT FROM AUTHOR]

The rate of chronic kidney disease (CKD) is increasing globally, and it is caused by continuous damage to kidney tissue. With time the renal damage becomes irreversible, leading to CKD development. In females, post-menopause lack of estrogen supply has been described as a risk factor for CKD development, and studies targeting post-menopause CKD are scarce. In the present study, we used exosomes isolated from bone marrow mesenchymal stem/stromal cells (BM-MSCs) to test their therapeutic potential against the development of CKD. At first, the menopause model was achieved by surgical bilateral ovariectomy in female albino rats. After that, 100 µg of exosomes was given to ovariectomized rats, and the study continued for 2 months. Changes in urine volume, urine protein content, kidney function biochemical parameters (creatinine and BUN), kidney antioxidant parameters (SOD, GPx and CAT), histological changes, immunohistochemical levels of caspase 3, and the gene expression of NGAL (related to kidney damage), TGFβ1 and αSMA (related to fibrosis and EMT), and caspase 3 (related to apoptosis) were studied. After the ovariectomy, the occurrence of CKD was confirmed in the rats by the drastic reduction of serum estrogen and progesterone levels, reduced urine output, increased urinary protein excretion, elevated serum creatinine and BUN, reduced GPx SOD, and CAT in kidney tissue, degenerative and fibrotic lesions in the histopathological examination, higher immunohistochemical expression of caspase 3 and increased expression of all studied genes. After exosomes administration, the entire chronic inflammatory picture in the kidney was corrected, and a near-normal kidney structure and function were attained. This study shows for the first time that BM-MSCs exosomes are potent for reducing apoptosis and fibrosis levels and, thus, can reduce the chronic damage of the kidneys in females that are in their menopause period. Therefore, MSCs-derived exosomes should be considered a valuable therapy for preserving postmenopausal kidney structure and function and, subsequently, could improve the quality of females' life during menopause. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is an important global disease its rates are increasing worldwide. CKD is caused by injuries to kidney tissue that exceeds the rate of regeneration, which with time lead to irreversible renal damage and CKD become evident. In females, diminished estrogen supply in the postmenopausal period is associated with greater risk for developing CKD. In this study we isolated exosomes from bone marrow mesenchymal stem/stromal cells (BM-MSCs) and tested their therapeutic effects on post-menopause CKD (PM-CKD) and compared their effects with BM-MSCs. The menopause model was achieved by bilateral ovariectomy in 8-months-old female albino rats, then no treatment, 2 million BM-MSCs or 100 μg of exosomes (Exo) was given intravenously in tail vein to ovariectomized rats and the study continued for 8 weeks post-ovariectomy. Changes in weight, urine volume, urine protein content, kidney function biochemical parameters (creatinine and BUN), Kidney oxidative stress (MDA), kidney antioxidant parameters (SOD, GPx and CAT), histopathological changes, immunohistochemical expression of KIM-1 and, finally, genes related to renal damage (peroxiredoxin-3, KIM-1 and ICAM-1) and inflammation (TNF-α, Cox2 and IL-6) were recorded for all study groups. Post-ovariectomy there was an increased body weight, drastic reduction of estrogen and progesterone levels, reduced urine output, increased urinary protein excretion, elevated serum creatinine and BUN, increased MDA and reduced GPx SOD, and CAT in kidney tissue, chronic inflammation, degenerative and fibrotic lesions in histopathological examination, high expression of KIM-1 immunohistochemically and changes in gene expression analyses all pointing to the development of CKD in the study rats. In the PM-CKD groups receiving BM-MSCs or Exo, the whole chronic inflammatory picture was completely reversed towards a much normal kidney structure and function. The improvements were more observable with Exo compared to BM-MSCs. Overall, our results show for the first time that exosomes isolated from BM-MSCs are more potent in reducing chronic inflammatory changes in the kidney of postmenopausal females compared to the cell-based approach using BM-MSCs. Therefore, MSCs-derived exosomes are a promising therapeutic approach for preserving postmenopausal kidney structure and function and, subsequently, should improve the quality of life of postmenopausal females. [Display omitted] • MSCs exosomes are a promising therapy for postmenopause CKD (PM-CKD). • MSCs exosomes reduce oxidative stress and maintain antioxidant defenses in PM-CKD. • MSCs exosomes reduce inflammatory and degenerative changes in PM-CKD. • MSCs exosomes reserve kidney histological architecture and functionality in PM-CKD. [ABSTRACT FROM AUTHOR]

Abstract Background There is high incidence of liver and kidney diseases worldwide but medicinal plants may provide remedy. This study evaluated and compared the protective effects of Cassia spectabilis extract (CSE) and Newbouldia laevis extract (NLE) against diclofenac (DF) induced hepatorenal oxidative damage in rats. Methods Twenty four rats were divided into 4 groups with 6 rats in each. Normal saline was given to the rats in group I while those in groups III and IV were treated with 250 mg/kg b. wt. CSE and NLE respectively for 28 days by oral gavages. Those in groups II to IV were exposed to 10 mg/kg DF in the last 7 days of treatment. Serum was separated from the blood and used for estimations of hepatorenal injury markers while the homogenized tissue supernatants were used for assays of oxidative stress markers. Results There was a significant (p

Background Nephrotoxicity, especially acute kidney injury (AKI), is the main dose-limiting toxicity of cisplatin. Although recent studies showed that curcumin prevented cisplatin-induced AKI effectively, further studies to understand the mechanism are required. Methods We established an AKI mouse model. Male C57BL/6 mice were assigned to three groups: saline group (control), cisplatin group (CP), and curcumin + cisplatin group (CP + Cur). The CP group received a single intraperitoneal (i.p.) injection of cisplatin, while the control group received saline. The CP + Cur group received i.p. curcumin three days before cisplatin injection and curcumin administered for another three days until the day before euthanization. Renal injury was assessed by serological and histological analysis. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the phosphatase and tensin homolog (PTEN), and microRNA (miR)-181a expression in the renal tissues. Bioinformatics prediction and western blotting methods validated the targets of miR-181a in vitro. Results Curcumin treatment alleviated cisplatin-induced nephrotoxicity as validated by the blood urea nitrogen (BUN) values, and histological analysis of kidneys. At the molecular level, curcumin treatment decreased miR-181a expression level, which was induced by cisplatin and restored the in vivo expression of PTEN, which was suppressed by cisplatin. We verified the direct regulation of PTEN by miR-181a in cultured human embryonic kidney 293T cells. Conclusions We showed the involvement of miR-181a/PTEN axis in the renoprotective effect of curcumin against cisplatin-induced AKI, and provide new evidence on the ability of curcumin to alleviate cisplatin-induced nephrotoxicity.

BackgroundHypertension has been shown to be an important risk factor in IgA nephropathy (IgAN). The 2021 the Kidney Disease Improving Global Outcomes (KDIGO) Guideline proposes a target systolic blood pressure (SBP) of less than 120 mmHg in patients with Chronic Kidney Disease (CKD) not receiving dialysis. However, whether lowering SBP from 1.0 g/d, CKD 1-3a stage, but not those with proteinuria ≤ 1.0 g/d and CKD 3b-4 stage.ConclusionsIn patients with IgAN, SBP was independently associated with composite kidney failure events. Lowering SBP from

Chronic kidney disease (CKD) is an increasing global health burden. Current treatments for CKD include therapeutics to target factors that contribute to CKD progression, including renin–angiotensin–aldosterone system inhibitors, and drugs to control blood pressure and proteinuria control. Recently, associations between chronic disease processes and the human microbiota and its metabolites have been demonstrated. Dysbiosis—a change in the microbial diversity—has been observed in patients with CKD. The relationship between CKD and dysbiosis is bidirectional; gut-derived metabolites and toxins affect the progression of CKD, and the uremic milieu affects the microbiota. The accumulation of microbial metabolites and toxins is linked to the loss of kidney functions and increased mortality risk, yet renoprotective metabolites such as short-chain fatty acids and bile acids help restore kidney functions and increase the survival rate in CKD patients. Specific dietary interventions to alter the gut microbiome could improve clinical outcomes in patients with CKD. Low-protein and high-fiber diets increase the abundance of bacteria that produce short-chain fatty acids and anti-inflammatory bacteria. Fluctuations in the urinary microbiome are linked to increased susceptibility to infection and antibiotic resistance. In this review, we describe the potential role of the gut, urinary and blood microbiome in CKD pathophysiology and assess the feasibility of modulating the gut microbiota as a therapeutic tool for treating CKD.

Benzo [a] pyrene (B[a]P) is a potent mutagen and carcinogen, considered one of the commonest concomitants in the environment. The study aimed to evaluate the effect of catechin hydrate on benzo pyrene-induced kidney toxicity. Thirty-six adult male albino rats were divided into six groups: group I untreated control, group II received 10 mL/kg of corn oil (solvent of benzo [a] pyrene) twice a week, group III received 1 mL/kg 0.5% dimethyl sulfoxide (DMSO) (solvent of catechin) once per day, group IV received 50 mg/kg body weight of benzo[a]pyrene twice a week, group V received 20 mg/kg body weight of catechin in 1 mL/kg 0.5% DMSO once daily, and group VI received both catechin+benzo [a] pyrene with the same doses. All treatment was given by oral gavage for four weeks. At the end of the experiment, blood samples were collected for biochemical investigations, tissues were obtained for genotoxicity, RT-PCR, and histopathological studies. B[a]P exposure induced an increase in serum urea and creatinine levels along with severe renal histopathological changes. Our results showed a subsequent decrease in the antioxidant enzyme activities (catalase and superoxide dismutase), and conversely, (malondialdehyde) levels markedly elevated. Also, B[a]P induced DNA damage as well as activated an apoptotic pathway confirmed by upregulation of Bax, caspase-3, and downregulation of Bcl-2 expression. However, treatment with catechin-corrected kidney functions and antioxidant enzymes as well as regulated apoptosis. Histological results also supported the protective effects of catechin. These findings suggested that catechin hydrate is an effective natural product that attenuates benzo pyrene-induced kidney toxicity. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of immunosuppressive monotherapy agents were evaluated for immunoglobulin A nephropathy (IgAN) using a network meta-analysis approach.Methods: Randomized controlled trials (RCTs) published prior to October 1, 2019, using immunosuppressive agents for treating IgAN, were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science databases. Relative risks (RRs) or standard mean differences with 95% confidence intervals (CIs) were estimated using the random-effects model. The primary outcomes were clinical remission, end-stage renal disease (ESRD), and serious adverse events (SAEs). The secondary outcomes were urinary protein excretion and serum creatinine.Results: Twenty-five RCTs with 2,005 participants were deemed eligible. Six medications were evaluated: corticosteroids, mycophenolate mofetil (MMF), tacrolimus (TAC), cyclosporine, leflunomide, and hydroxychloroquine (HCQ). Steroids (RR 1.50, 95% CI 1.17–1.93), MMF (RR 2.05, 95% CI 1.15–3.65), TAC (RR 3.67, 95% CI 1.06–12.63), and HCQ (RR 3.25, 95% CI 1.05–10.09) significantly improved clinical remission rates compared to supportive care alone. Only steroids reduced the risk of ESRD (RR 0.35, 95% CI 0.12–0.98); however, there were significantly more SAEs than in the control group (RR 2.90, 95% CI 1.37–6.13). No significantly different effects in serum creatinine levels were found among the therapies. MMF showed no significant improvement in remission when excluding studies with a follow-up of fewer than 2 years in the sensitivity analysis (RR 1.41, 95% CI 0.40–4.92). The effect of TAC in the decrease of proteinuria was reversed after discontinuing medication for 3 months; the long-term effects of HCQ could not be evaluated due to the short follow-up duration.Conclusion: Corticosteroids might induce remission and increase renal survival in IgAN; however, adverse reactions should be taken into consideration. MMF, TAC, and HCQ might improve the remission of proteinuria when treating IgAN, but showed no superiority compared to steroids, and the long-term effects require further study.

The rate of chronic kidney disease (CKD) is increasing globally, and it is caused by continuous damage to kidney tissue. With time the renal damage becomes irreversible, leading to CKD development. In females, post-menopause lack of estrogen supply has been described as a risk factor for CKD development, and studies targeting post-menopause CKD are scarce. In the present study, we used exosomes isolated from bone marrow mesenchymal stem/stromal cells (BM-MSCs) to test their therapeutic potential against the development of CKD. At first, the menopause model was achieved by surgical bilateral ovariectomy in female albino rats. After that, 100 µg of exosomes was given to ovariectomized rats, and the study continued for 2 months. Changes in urine volume, urine protein content, kidney function biochemical parameters (creatinine and BUN), kidney antioxidant parameters (SOD, GPx and CAT), histological changes, immunohistochemical levels of caspase 3, and the gene expression of NGAL (related to kidney damage), TGFβ1 and αSMA (related to fibrosis and EMT), and caspase 3 (related to apoptosis) were studied. After the ovariectomy, the occurrence of CKD was confirmed in the rats by the drastic reduction of serum estrogen and progesterone levels, reduced urine output, increased urinary protein excretion, elevated serum creatinine and BUN, reduced GPx SOD, and CAT in kidney tissue, degenerative and fibrotic lesions in the histopathological examination, higher immunohistochemical expression of caspase 3 and increased expression of all studied genes. After exosomes administration, the entire chronic inflammatory picture in the kidney was corrected, and a near-normal kidney structure and function were attained. This study shows for the first time that BM-MSCs exosomes are potent for reducing apoptosis and fibrosis levels and, thus, can reduce the chronic damage of the kidneys in females that are in their menopause period. Therefore, MSCs-derived exosomes should be considered a valuable therapy for preserving postmenopausal kidney structure and function and, subsequently, could improve the quality of females’ life during menopause.

The objective of this review article was to identify and examine current evidence surrounding the potential renoprotective effects of newer antidiabetic agents such as sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucose-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors. A literature search of MEDLINE and PubMed (January 2000 to April 2019) was performed using the following search terms: "diabetes treatment," "renoprotection," "kidneys," "SGLT-2 inhibitors," "GLP-1 receptor agonists," "DPP-4 inhibitors," and the drug names in each of those classes as well as any combination of these terms. Literature was excluded if published in a language other than English, performed in nonhuman subjects, did not include patients from the United States, was nonrandomized, or the data were available from poster presentations. There were 11 studies that met the search criteria. The majority of the studies focused on renal outcomes as secondary end points and looked at albuminuria, estimated glomerular filtration rate changes from baseline, urinary albumin-to-creatinine ratio, serum creatinine, and need for renal replacement therapy. There are fewer studies that focused on renal protection as a primary end point. After reviewing the available literature, the use of SGLT-2 inhibitors and GLP-1 agonists in addition to standard of care may be considered in patients with or at risk of developing chronic kidney disease. SGLT-2 inhibitors and GLP-1 agonists should be considered when patients' diabetes is no longer well controlled with metformin. Other factors such as cost, cardiovascular disease, and other comorbidities may also be taken into consideration when recommending therapy for patients. [ABSTRACT FROM AUTHOR]

Developing new therapeutic drugs to prevent ischemia/reperfusion (I/R)-induced renal injuries is highly pursued. Liposomal encapsulation of spironolactone (SP) as a mineralocorticoid antagonist increases dissolution rate, bioavailability and prevents the drug from degradation. In this context, this work develops a new formulation of oil-in-water type microemulsions to enhance the bioavailability of SP. The size of the SP-loaded microemulsion was about 6.0 nm by dynamic light scattering analysis. Briefly, we investigated the effects of nano-encapsulated SP (NESP) on renal oxidative stress, biochemical markers and histopathological changes in a rat model of renal I/R injury. Forty eight male Wistar rats were divided into six groups. Two groups served as control and injury model (I/R). Two groups received "conventional" SP administration (20 mg/kg) and NESP (20 mg/kg), respectively, for two days. The remaining two groups received SP (20 mg/kg) and NESP (20 mg/kg) two days before induction of I/R. At the end of the experiments, serum and kidneys of rats underwent biochemical, molecular and histological examinations. Our results showed that I/R induces renal oxidative stress, abnormal histological features and altered levels of renal biomarkers. Administration of SP in healthy animals did not cause any significant changes in the measured biochemical and histological parameters compared to the control group. However, SP administration in the I/R group caused some corrections in renal injury, although it could not completely restore I/R-induced renal oxidative stress and kidney damage. On the contrary, NESP administration restored kidney oxidative injury via decreasing renal lipid peroxidation and enhancing glutathione, superoxide dismutase and catalase in kidneys of the I/R group. The deviated serum levels of urea, creatinine, total proteins and uric acid were also normalized by NESP administration. Furthermore, NESP protected against renal abnormal histology features induced by I/R. Therefore, NESP has beneficial effects in preventing kidney damage and renal oxidative stress in a rat model of I/R, which deserves further evaluations in the future. [ABSTRACT FROM AUTHOR]

Gentamicin (GM) is an effective antibiotic against gram-negative bacterial infection. However, GM can produce nephrotoxicity. Stachys lavandulifolia Vahl. (SL) is extensively used in folk medicine as herbal tea and has strong antioxidative effects. The aim of this study was to investigate the protective effect of SL on GM-induced nephrotoxicity in rats. In this study, forty-two male Wistar rats were randomly divided into six equal groups (N = 7 each): control (group I), GM-treated (group II), SL200 mg/kg + GM-treated (group III), SL400 mg/kg + GM-treated (group IV), SL200 mg/kg-treated (group V), and SL400 mg/kg-treated (group VI) groups. The treatment procedures continued for 10 days. At the end of the experiment, serum and the kidneys of all groups were harvested for histological and biochemical examination. No statistical significant improvement in histological and biochemical indices was shown at 200 mg/kg of SL treatment in group III compared with group II; however, at 400 mg/kg of SL, normalized serum levels of uric acid (P < 0.001), urea (P < 0.001), creatinine (P < 0.01), and total proteins (P < 0.05) were shown in group IV. Treatment with SL400 mg/kg also corrected the increased relative kidney weight in GM-treated animals (P < 0.05). GM nephrotoxicity was shown by elevated levels of malondialdehyde (P < 0.001) and decreased amounts of catalase (P < 0.001), superoxide dismutase (P < 0.01), and glutathione (P < 0.01) in renal tissue. The oxidative injury induced by GM was prevented by SL400 mg/kg treatment. Such treatment also normalized abnormal renal histology induced by GM. These data suggest that treatment with SL extract may be helpful to reduce gentamicin-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic 3',5' GMP (cGMP) signaling plays a central role in regulation of diverse processes including smooth muscle relaxation, inflammation, and fibrosis. sGC is activated by the short-lived physiologic mediator NO. sGC stimulators are small-molecule compounds that directly bind to sGC to enhance NO-mediated cGMP signaling. Olinciguat, (R)-3,3,3-trifluoro-2-(((5-fluoro-2-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl)pyrimidin-4-yl)amino)methyl)-2-hydroxypropanamide, is a new sGC stimulator currently in Phase 2 clinical development. To understand the potential clinical utility of olinciguat, we studied its pharmacokinetics, tissue distribution, and pharmacologic effects in preclinical models. Olinciguat relaxed human vascular smooth muscle and was a potent inhibitor of vascular smooth muscle proliferation in vitro. These antiproliferative effects were potentiated by the phosphodiesterase 5 inhibitor tadalafil, which did not inhibit vascular smooth muscle proliferation on its own. Olinciguat was orally bioavailable and predominantly cleared by the liver in rats. In a rat whole body autoradiography study, olinciguat-derived radioactivity in most tissues was comparable to plasma levels, indicating a balanced distribution between vascular and extravascular compartments. Olinciguat was explored in rodent models to study its effects on the vasculature, the heart, the kidneys, metabolism, and inflammation. Olinciguat reduced blood pressure in normotensive and hypertensive rats. Olinciguat was cardioprotective in the Dahl rat salt-sensitive hypertensive heart failure model. In the rat ZSF1 model of diabetic nephropathy and metabolic syndrome, olinciguat was renoprotective and associated with lower circulating glucose, cholesterol, and triglycerides. In a mouse TNFα-induced inflammation model, olinciguat treatment was associated with lower levels of endothelial and leukocyte-derived soluble adhesion molecules. The pharmacological features of olinciguat suggest that it may have broad therapeutic potential and that it may be suited for diseases that have both vascular and extravascular pathologies.

Nephrotoxicity, especially acute kidney injury (AKI), is the main dose-limiting toxicity of cisplatin. Although recent studies showed that curcumin prevented cisplatin-induced AKI effectively, further studies to understand the mechanism are required. We established an AKI mouse model. Male C57BL/6 mice were assigned to three groups: saline group (control), cisplatin group (CP), and curcumin + cisplatin group (CP + Cur). The CP group received a single intraperitoneal (i.p.) injection of cisplatin, while the control group received saline. The CP + Cur group received i.p. curcumin three days before cisplatin injection and curcumin administered for another three days until the day before euthanization. Renal injury was assessed by serological and histological analysis. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the phosphatase and tensin homolog (PTEN), and microRNA (miR)-181a expression in the renal tissues. Bioinformatics prediction and western blotting methods validated the targets of miR-181a in vitro. Curcumin treatment alleviated cisplatin-induced nephrotoxicity as validated by the blood urea nitrogen (BUN) values, and histological analysis of kidneys. At the molecular level, curcumin treatment decreased miR-181a expression level, which was induced by cisplatin and restored the in vivo expression of PTEN, which was suppressed by cisplatin. We verified the direct regulation of PTEN by miR-181a in cultured human embryonic kidney 293T cells. We showed the involvement of miR-181a/PTEN axis in the renoprotective effect of curcumin against cisplatin-induced AKI, and provide new evidence on the ability of curcumin to alleviate cisplatin-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

Background. Benign prostate hyperplasia (BPH) is a non-cancerous enlargement of the prostate gland as a result of an overgrowth of prostate cells and muscles found around the prostatic transition. It is age-dependent and characterized by benign prostate enlargement (BPE), bladder outlet obstruction (BOO) and lower urinary tract symptoms (LUTS). The study investigated the effects of a combined extract of Funtumia africana and Abutilon mauritianum leaves (CEFA) on the lipid profile and renal indices of testosterone-induced BPH in male albino rats. Materials and methods. Thirty (30) male albino rats (100-150 g) divided into 5 groups (n = 6) were used. BPH was induced subcutaneously with 2 ml of testosterone propionate. Groups 1-3 served as normal, BPH untreated and standard drug controls respectively, while groups 4 and 5 were BPH-induced and treated with low (200 mg/kg) and high (600 mg/kg) doses of CEFA respectively. After twenty-eight days of treatment, the rats were anaesthetized, blood was collected by cardiac puncture and the sera centrifuged to determine lipid profile and renal indices using standard analytical procedures. Results. The acute toxicity result of CEFA indicated no mortality or adverse reactions. The results of the lipid profile and renal function studies showed a significant (p < 0.05) increase in triacylglycerol (TAG), total cholesterol (TC), urea and creatinine, and a significant (p < 0.05) decrease in high-density lipoprotein (HDL) concentrations in the BPH control group when compared to the normal control. Treatment with CEFA caused a significant (p < 0.05) decrease in TAG, urea and creatinine concentrations and a significant (p < 0.05) increase in HDL-C when compared to the untreated group. No significant (p > 0.05) difference was observed in serum concentrations of TC and low-density lipoprotein (LDL) in the treatment groups compared to the BPH control. The histopathological result indicated no toxic insult on the kidney tissues. Conclusion. The findings suggest that CEFA possesses antilipidaemic properties in terms of elevation and decrease in HDL and TAG concentrations respectively. Also, CEFA possesses renoprotective potential in terms of reducing urea and creatinine concentrations. [ABSTRACT FROM AUTHOR]

Glaucoma is a disease accompanied by a progressive degenerative lesion of the retinal ganglion cells and the optic nerve, being one of the leading causes of blindness all over the world. The search for the new drugs for the treatment of glaucoma, aimed directly at reducing intraocular pressure and neuroprotection, and in some cases neuroregeneration, is impossible without the creation of appropriate experimental models. The current variety of models does not always provide a sufficient level of functional changes or is accompanied by a number of disadvantages that impede further research. There is a wide variety of glaucoma models. This article discusses the main ones, as well as describes the advantages and disadvantages of glaucoma models performed in small laboratory animals. Hypertensive and normotensive models of glaucoma are described, which correlates with human pathogenesis. This review forms a representation and describes most models of glaucoma in rodents. The search for models of certain forms of glaucoma remains as an indisputable fact. Based on testable hypothesis and experimental validity this data should be interpreted in the context of the experiment. Despite modern achievements, the improvement of experimental techniques and the search for new models continues till the present day. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess changes in the estimated glomerular filtration rate (eGFR) in gouty patients with chronic kidney disease (CKD) using a "treat-to-target" (T2T) approach in gout. This multicenter observational retrospective study included patients diagnosed with gout and CKD stage 3 taking xanthine oxidase inhibitors (XOIs) (allopurinol or febuxostat) for at least 12 months. All patients were treated using a T2T strategy according to national gout guidelines to achieve the target levels of serum uric acid (sUA; < 5–6 mg/dl) within 6 months of the first visit. The primary outcome was to assess changes in eGFR. The effects of independent variables were analyzed over eGFR in a linear mixed-effects (LME) model. Fifty patients with gout and CKD stage 3 treated with XOIs with a T2T strategy for 12 months were included. Eighty-two percent of the patients achieved the sUA target during the study period. The improvement seen in eGFR was higher during the first 6 months, showing a median increase of 7.54 ml/min/m2 (SE = 1.25) and trending towards stability over 12 months. For every 1 mg/dl of decrease in sUA, an improvement of 1.5 ml/min/m2 in eGFR was observed (coefficient ± SE: − 1.58 ± 0.26) (p < 0.001) with no differences between type and dosage of XOIs treatment, colchicine administration, age, sex, and smoking status. A reduction in sUA levels using a T2T approach with XOIs at an optimal dose is possible and could help conserve and improve renal function in gouty patients with CKD stage 3. [ABSTRACT FROM AUTHOR]

Background: There is high incidence of liver and kidney diseases worldwide but medicinal plants may provide remedy. This study evaluated and compared the protective effects of Cassia spectabilis extract (CSE) and Newbouldia laevis extract (NLE) against diclofenac (DF) induced hepatorenal oxidative damage in rats. Methods: Twenty four rats were divided into 4 groups with 6 rats in each. Normal saline was given to the rats in group I while those in groups III and IV were treated with 250 mg/kg b. wt. CSE and NLE respectively for 28 days by oral gavages. Those in groups II to IV were exposed to 10 mg/kg DF in the last 7 days of treatment. Serum was separated from the blood and used for estimations of hepatorenal injury markers while the homogenized tissue supernatants were used for assays of oxidative stress markers. Results: There was a significant (p < 0.01) increase in the levels of ALT, AST, GGT, MDA, creatinine and BUN but a significant (p < 0.01) decrease in the levels of SOD, CAT, GPx, GST, GSH and G6Pase of DF-exposed rats when compared with normal control. However, treatment of DF-exposed rats with CSE and NLE significantly (p < 0.01) increased the levels of SOD, CAT, GPx, GST, GSH, and G6Pase but significantly (p < 0.01) reduced the levels of ALT, AST, GGT, MDA, creatinine and BUN when compared with DF control. Conclusion: The current findings showed that treatments with CSE and NLE may have protective effects against DF-induced hepatorenal oxidative damage in rats, attributed to certain phytochemicals, but CSE has greater bioactivity than NLE. [ABSTRACT FROM AUTHOR]

The aim of current study was to assess the antioxidant and renoprotective effects of Stachys pilifera Benth (S.P.B.) hydroalcoholic extract on nephrotoxicity induced with cisplatin (CP). Adult rats with bodyweight of 180–220 g were divided into five groups (n = 7) treated as follows: group 1, control; group 2, CP; group 3, pretreatment with S.P.B. before CP; group 4, posttreatment with S.P.B. after CP; and, group 5, S.P.B. extract. A single dose of CP (7 mg/kg) was intraperitoneally injected on the fifth day and hydroalcoholic extract of S.P.B. (500 mg kg–1 day–1) was orally administered. The levels of oxidative stress markers, biochemical tests, and histopathological staining were assayed in serum and renal tissue. Also, the chemical composition of S.P.B. extract was determined by GC‐MS analysis. The main compositions of S.P.B. extract identified by GC‐MS analysis, were hexadeca‐2,6,10,14‐tetraen‐1‐ol, 3,7,11,16‐tetramethyl (24.77%), thymol (14.1%), and linolenic acid (13.4%). In groups treated and pretreated with S.P.B., blood urea nitrogen, creatinine, malondialdehyde, and nitric oxide metabolite in serum as well as malondialdehyde and protein carbonyl content of kidney tissues were significantly decreased in comparison to CP group; in contrast, total thiol group showed a significant increase in treated group as compared to CP group. Furthermore, histological investigation indicated that treatment with S.P.B. improved renal damages induced by CP. The current study showed that S.P.B. hydroalcoholic extract improved the biochemical parameters and kidney function as well as restored antioxidant activity in CP‐induced nephrotoxicity. However, it needs more investigations to define the mechanism of S.P.B. action. Practical applications: In different regions of Iran, Stachys is demonstrated by 34 species, out of which 13 are endemic, one of these endemic species is Stachys pilifera Benth (S.P.B.). The oil of S.P.B. is mainly consisted of cis‐chrysanthenyl acetate, cis‐chrysanthenol, spathulenol, β‐caryophyllene, linalool, and terpinen‐4‐ol. Moreover, phytochemical studies have shown the presence of compounds such as diterpenes, phenylethanoid glycosides, saponins, terpenoides, and flavonoids in Stachys species. The aerial parts of S.P.B. are consumed as herbal tea to treat several disorders, for example, infections, asthma, and rheumatoid arthritis in Iranian folk medicine. The aim of current study was to evaluate the antioxidant and protective effects of S.P.B. hydroalcoholic extract on nephrotoxicity induced with cisplatin (CP). The current study showed that S.P.B. hydroalcoholic extract improved the biochemical parameters and kidney function as well as restored antioxidant activity in CP‐induced nephrotoxicity. However, it needs more researches to define the mechanism of S.P.B. action. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic 3',5' GMP (cGMP) signaling plays a central role in regulation of diverse processes including smooth muscle relaxation, inflammation, and fibrosis. sGC is activated by the short-lived physiologic mediator NO. sGC stimulators are small-molecule compounds that directly bind to sGC to enhance NO-mediated cGMP signaling. Olinciguat, (R)-3,3,3-trifluoro-2-(((5-fluoro-2-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl)pyrimidin-4-yl)amino)methyl)-2-hydroxypropanamide, is a new sGC stimulator currently in Phase 2 clinical development. To understand the potential clinical utility of olinciguat, we studied its pharmacokinetics, tissue distribution, and pharmacologic effects in preclinical models. Olinciguat relaxed human vascular smooth muscle and was a potent inhibitor of vascular smooth muscle proliferation in vitro. These antiproliferative effects were potentiated by the phosphodiesterase 5 inhibitor tadalafil, which did not inhibit vascular smooth muscle proliferation on its own. Olinciguat was orally bioavailable and predominantly cleared by the liver in rats. In a rat whole body autoradiography study, olinciguat-derived radioactivity in most tissues was comparable to plasma levels, indicating a balanced distribution between vascular and extravascular compartments. Olinciguat was explored in rodent models to study its effects on the vasculature, the heart, the kidneys, metabolism, and inflammation. Olinciguat reduced blood pressure in normotensive and hypertensive rats. Olinciguat was cardioprotective in the Dahl rat salt-sensitive hypertensive heart failure model. In the rat ZSF1 model of diabetic nephropathy and metabolic syndrome, olinciguat was renoprotective and associated with lower circulating glucose, cholesterol, and triglycerides. In a mouse TNFα-induced inflammation model, olinciguat treatment was associated with lower levels of endothelial and leukocyte-derived soluble adhesion molecules. The pharmacological features of olinciguat suggest that it may have broad therapeutic potential and that it may be suited for diseases that have both vascular and extravascular pathologies. [ABSTRACT FROM AUTHOR]

Purpose: To study the mechanism involved in metformin (DMBG)-induced reduction of albuminuria in spontaneously-hypertensive rats (SHRs). Methods: The SHRs were divided into DMBG SHR group (n = 30) given DMBG (300 mg/kg) and NC SHR group (n = 10) given distilled water (2 ml/day), while Wistar-Kyoto rats (WKY) rats were divided into DMBG WKY group (n = 30) given DMBG (300 mg/kg ) and NC WKY group (n = 10) administered distilled water (2 ml/day). Urinary protein levels were measured and compared. Inflammatory infiltration in renal tissue, and expression of vascular endothelial growth factor (VEGF) were assessed. Abdominal aortic blood was used to measure serum levels of creatinine and blood urea nitrogen (BUN). Results: Urinary protein was markedly elevated in SHRs, while BUN in SHRs was lowered, relative to WKY rats (p < 0.05). Moreover, inflammatory cell population was lower in DMBG SHRs group than in WKY rats (p < 0.05). Kidney expressions of VEGF in SHR and WKY rats treated with metformin were significantly reduced, relative to those in untreated rats, but VEGF-A in DMBG SHR rats was markedly elevated, relative to NC SHR group, and was also raised in DMBG WKY, when compared with NC WKY rats (p < 0.05). Conclusion: Metformin reduces albuminemia in spontaneously hypertensive rats by up-regulating VEGF expression, thereby exerting renoprotective effect. This finding provides ideas for research and development of other therapeutic approaches. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is one of the most prevalent chronic diseases and affects between 10 and 14 % of the world's population. The World Health Organization estimates that by 2040, the disease will be fifth in prevalence. End-stage CKD is characterized by renal fibrosis, which can eventually lead to kidney failure and death. Renal fibrosis develops due to multiple injuries and involves oxidative stress and inflammation. In the human body, nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in the expression of antioxidant, anti-inflammatory, and cytoprotective genes, which prevents oxidative stress and inflammation damage. Heme oxygenase (HO-1) is an inducible homolog influenced by heme products and after exposure to cellular stress inducers such as oxidants, inflammatory chemokines/cytokines, and tissue damage as an outcome or downstream of Nrf2 activation. HO-1 is known for its antioxidative properties, which play an important role in regulating oxidative stress. In renal diseases-induced tissue fibrosis and xenobiotics-induced renal fibrosis, Nrf2/HO-1 has been targeted with promising results. This review summarizes these studies and highlights the interesting bioactive compounds that may assist in attenuating renal fibrosis mediated by HO-1 activation. In conclusion, Nrf2/HO-1 signal activation could have a renoprotective effect strategy against CKD caused by oxidative stress, inflammation, and consequent renal fibrosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Rudgea viburnoides is widely found in the Brazilian Cerrado, and commonly used in Brazilian folk medicine. In this study, we evaluated the effects of prolonged administration of the aqueous extract from R. viburnoides leaves (AERV) on impaired redox status, renal dysfunction, and cardiovascular damage in 2K1C hypertensive rats, as well as its chemical composition by LC-DAD-MS. Renal hypertension (two kidney, one-clip model) was surgically induced in male Wistar rats and AERV (30, 100 and 300 mg/kg) was administered orally five weeks after surgery for 28 days. Renal function was assessed and urinary electrolytes, pH, and density were measured. Electrocardiography, blood pressure and heart rate were recorded. Cardiac and mesenteric vascular beds were isolated for cardiac morphometry and evaluation of vascular reactivity, and aortic rings were also isolated for measurement of cyclic guanosine monophosphate levels, and the redox status was assessed. Prolonged treatment with AERV preserved urine excretion and electrolyte levels (Na+, K+, Ca2+ and Cl−), reversed electrocardiographic changes, left ventricular hypertrophy and changes in vascular reactivity induced by hypertension, and reduced blood pressure and heart rate. This effect was associated with a positive modulation of tissue redox state, activation of the NO/cGMP pathway, and inhibition of the angiotensin-converting enzyme. Glycosylated iridoids, chlorogenic acids, glycosylated triterpenes, O-glycosylated flavonols, and triterpenoid saponins were annotated. AERV showed no acute toxicity in female Wistar rats. Therefore, AERV treatment reduced the progression of cardiorenal disease in 2K1C hypertensive rats, which can be involved with an important attenuation of oxidative stress, angiotensin-converting enzyme inhibition, and activation of the NO/cGMP pathway.