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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]

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.

Background: The prevention against diabetic nephropathy is still required due to the limitation of the current therapeutic strategy. Based on the effect of antioxidants on the restoration of renal dysfunction in diabetic nephropathy, we hypothesized that the combination extract of seed of Mangifera indica or mango var. Namdokmai and aerial part of Polygonum odoratum or Vietnamese coriander (MPO) which possessed antioxidant activity might prevent diabetic nephropathy and be safe for consumption. Objective: To test this hypothesis, we aimed to determined acute toxicity and renoprotective effect of MPO in STZ-diabetic rats. Materials and Methods: Acute toxicity was assessed in Wistar rats. Single administration of MPO at dose of 5,000 mg.kg-1 BW failed to produce mortality and related toxicity signs. To test renoprotective effect, diabetic rats were induced by a single injection of streptozotocin (STZ). STZ-diabetic rats were orally given MPO at doses of 2, 10 and 50 mg.kg-1 BW for 10 weeks. Then, they were determined body weight, kidney weight, urine volume, urine specific gravity and blood biochemical parameters at the end of experiment. In addition, kidneys were collected and determined histomorphology, nitric oxide synthase (NO), NF-kappa B (NF-kB), vascular endothelial growth factor (VEGF), aldose reductase (AR) and oxidative stress status. Results: Low dose of MPO significantly improved creatinine clearance while medium and high doses of MPO significantly improved albuminuria. MPO also improved Bowman space, glomerular tuft, eNOS, oxidative stress status and NF-kB but no significant change of VEGF and AR were observed in kidney. Therefore, the possible underlying mechanism of MPO might be partly associated with the improvement of kidney structures, oxidative stress status, eNOS and NF-kB in kidney. Conclusion: Our data suggest that MPO is the potential candidate of renoprotectant against diabetic nephropathy but sub chronic toxicity and clinical trial are still essential. [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]

The genus Agrimonia L. of the family Rosaceae Juss. is known to include valuable medicinal plants. Agrimony is well known for its beneficial effects in various diseases such as liver complaints, gall-bladder stones; diarrhea, edemas and kidney ailments. The contents of microelements in aerial parts of Agrimonia eupatoria, an official herbal drug, collected from wild samples in the suburb of Lviv city, Western Ukraine, have been determined by atomic absorption spectroscopy with electrothermal atomization (ААС/ЕА) on VARIAN AA 240Z after mineralization in the microwave Milestone Start D. The found quantities of trace elements in the analyzed samples were as follows: manganese – 46.9 µg/g, copper – 7.9 µg/g, selenium – 0.16 µg/g, lead – 0.15 µg/g, cadmium – 0.05 µg/g. The received research outcomes were compared with results of other known scientific investigations of the medicinal plant material. The determined amounts of lead and cadmium in the investigated samples of the herbal drug complied with the World Health Organization (WHO) requirements. The special attention is paid for pharmacological effects, related to its renal impact, contents of selenium and phenolic compounds that allows considering the herbal drug as a promising nephroprotective agent.

Context: Heartwood of Pterocarpus marsupium has been widely reported for its effect on diabetes clinical or preclinically. However, role in diabetic complications is yet to be revealed. Aims: To investigate the effect of alcoholic extract of the heartwood of Pterocarpus marsupiumin experimentally induced diabetic nephropathy in rats. Methods: The streptozotocin (STZ) 55 mg/kg, i.p., once daily induced diabetes in Sprague-Dawley rats. These animals were treated orally with alcoholic extract of P. marsupium (100, 200 and 400 mg/kg) or glimepiride (10 mg/kg) for 60 days. Body weight, blood glucose, glycosylated hemoglobin (HBA1c), biochemical markers of renal function were estimated on day 30 and at the end of study (day 60). Kidney weight measurement, oxidative stress markers such as lipid peroxidation (TBARS), catalase, superoxide dismutase, reduced glutathione were estimated in kidney tissues, and histopathological evaluation was carried out at the end of study period. Results: The administration of an alcoholic extract of P. marsupium showed a decrease in blood glucose, HBA1c, kidney weight, serum creatinine, blood urea nitrogen, serum uric acid, urea, urine volume, urine albumin and the level of TBARS. While the increase in urine creatinine, the activity of superoxide dismutase and glutathione were observed when compared to the diabetic control group. This effect was observed significantly at the highest dose of the plant extract. The histopathological study also confirmed that alcoholic extract prevented structural kidney damage. Conclusions: These results suggest that the alcoholic extract of P. marsupium has renoprotective effects against STZ induced diabetic nephropathy.

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.

Curcumin is a naturally polyphenolic compound used for hepatoprotective, thrombosuppressive, neuroprotective, cardioprotective, antineoplastic, antiproliferative, hypoglycemic, and antiarthritic effects. Kidney disease is a major public health problem associated with severe clinical complications worldwide. The protective effects of curcumin against nephrotoxicity have been evaluated in several experimental models. In this review, we discussed how curcumin exerts its protective effect against renal toxicity and also illustrated the mechanisms of action such as anti-inflammatory, antioxidant, regulating cell death, and anti-fibrotic. This provides new perspectives and directions for the clinical guidance and molecular mechanisms for the treatment of renal diseases by curcumin., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Acute kidney injury (AKI) is a major health threat worldwide. The literature on herbal intervention in AKI was searched from English and Chinese databases and reports were critically analyzed in terms of preventing AKI, promoting repair and regeneration, enhancing extrarenal clearance of uremic toxins, and preventing progression to chronic kidney disease (CKD). Altogether, 16 herbal formulae and a few extracts derived from individual herbs were reported to prevent or mitigate AKI in animal models induced by renal ischemia/reperfusion, cisplastin, gentamicin, glycerol, adenine, sepsis or physical exhaustion. Four formulae and six individual herbs were reported to accelerate recovery and/or to prevent CKD in established AKI animal models. Intrarectal herbal medicines, with or without simultaneous oral administration, were reported in six clinical trials and in an animal model to increase extrarenal clearance of uremic toxins. Additional 13 clinical trials reported oral or intravenous herbal interventions in AKI of different etiologies. Despite recurring problems, notably poor compliance with good practice guidelines for clinical trials and for authentication, naming and quality control of herbal materials, accumulating experimental data on the preventive effects of herbal medicines in AKI look encouraging and urge for better, definitive trials to guide clinical practice. Herbal enemas promoting extrarenal clearance of uremic toxins seem cost-effective, but better clinical evidence is certainly needed before any affirmative recommendation be made for AKI patients without access to dialysis. New frontiers, however, lie in those herbal remedies that promote repair/regeneration and prevent chronicity after AKI. Recent experimental data suggest that this may be possible.

Background: One of the medicinal plants widely used by the population in the treatment of hypertension, atherosclerosis and circulatory disorders is Cuphea carthagenensis (Jacq.) J.F. Macbr. (Lythraceae), popularly known as 'sete sangrias', being found in Brazil, Hawaii and in South Pacific Islands. Despite the widespread use of this species by the population, its long-term antihypertensive and cardioprotective activities have not yet been scientifically evaluated.Purpose: To evaluate the possible cardioprotective effects of an ethanol-soluble fraction obtained from C. carthagenensis (ESCC) using ovariectomized hypertensive rats to simulate a broad part of the female population over 50 years of age affected by hypertension. In addition, the molecular mechanism that may be responsible for its cardiorenal protective effects was also explored.Methods: Female Wistar rats were submitted to surgical procedures of bilateral ovariectomy and induction of renovascular hypertension (two-kidneys, one-clip model). The sham-operated group was used as negative control. ESCC was obtained and a detailed phytochemical investigation about its main secondary metabolites was performed. ESCC was orally administered at doses of 30, 100 and 300  mg/kg, daily, for 28 days, 5 weeks after surgery. Enalapril (15  mg/kg) was used as standard antihypertensive drug. Renal function was evaluated on days 1, 7, 14, 21 and 28. At the end of the experimental period, systolic, diastolic, mean arterial pressure and heart rate were recorded. The activity of the tissue enzymatic antioxidant system, thiobarbituric acid reactive substances, nitrotyrosine, nitrite, aldosterone and vasopressin levels, in addition to the activity of the angiotensin-converting enzyme were also evaluated. Additionally, vascular reactivity to acetylcholine, sodium nitroprusside, and phenylephrine, and the role of nitric oxide, prostaglandins, and K+ channels in the vasodilator response of ESCC on the mesenteric vascular bed were also investigated.Results: ESCC-treatment induced an important cardiorenal protective response, preserving renal function and preventing elevation of blood pressure and heart rate in ovariectomized hypertensive rats. In addition, prolonged treatment with ESCC recovered mesenteric vascular reactivity at all doses used. This effect was associated with an important modulation of the antioxidant defense system with a possible increase in NO bioavailability. Additionally, NO/cGMP activation and K+ channel opening-dependent vasodilator effect was observed on the mesenteric vascular bed, indicating a potential mechanism for the cardiovascular effects of ESCC.Conclusion: A 28-days ESCC treatment reduces the progression of the cardiorenal disease in ovariectomized hypertensive rats. These effects seem to be involved with an attenuation of oxidative and nitrosative stress, affecting endothelial nitric oxide production and K+ channel opening in smooth muscle cells. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a global healthcare problem; however until now, there is no effective treatment that can stop its progression. In this study, we aimed to investigate the effect of empagliflozin, a sodium-glucose linked transporter-2 inhibitor (SGLT2I) in a model of unilateral ureteric obstruction (UUO) in rats, as a model of progressive renal interstitial fibrosis in vivo and the possibility of inclusion of klotho protein. Rats were randomly divided into five groups: group 1: control group, group 2: UUO untreated group, group 3: prophylactic SGLT2I treatment before UUO, group 4: immediate SGLT2I treatment after UUO, and group 5: delayed SGLT2I treatment (this group received distilled water 1 week after UUO then empagliflozin for 2 weeks). At the end of the experiment period, animals were sacrificed, and kidney fibrotic and inflammatory parameters were measured. Also kidney sections were examined histopathologically for CTGF expression. UUO resulted in renal dysfunction and fibrosis through upregulating inflammatory cascade (NF-κB-TLR4) as well as many fibrotic pathways (as TGF-β1, αSMA, Wnt, CTGF, and fibronectin) with significant reduction in the klotho protein expression. We hypothesized that both prophylactic and immediate treatment with empagliflozin after UUO in rats exert more renoprotective effect in comparison with delayed treatment via enhancement of renal klotho expression and activity, for further investigations. [ABSTRACT FROM AUTHOR]

Background and Objectives: Dyslipidemia is gaining much attention among healthcare professionals because of its high association with the malfunctioning of a number of normal physiological and metabolic processes in the body. Obesity is directly interconnected with dyslipidemia and is said to be a denouement of hyperlipidemia and, if left untreated, may lead to intense damage to organs that are directly involved in fat metabolism. The objective of this study was to investigate the synergistic antiobesity and anti-hyperlipidemic activities along with hepato- and renoprotective potential of nanoemulsomes (NES) of lovastatin (LTN)-loaded ginger (GR) and garlic (GL) oils. Materials and Methods: LTN nanoemulsomes co-encapsulated with GR oil and GL oil were prepared by a thin hydration technique. Eight-week-old male Wistar rats weighing 200−250 g were induced with hyperlipidemia via a high-fat diet (HFD) comprising 40% beef tallow. Body weight, serum biochemical lipid parameters, and those for liver and kidney functions, serum TC, LDL-C, vLDL-C, HDL-C, TG, atherogenic index (AI), ALT, AFT, ALP, γ-GT, total protein (TP), serum albumin and globulin ratio (A/G), serum creatinine, blood urea nitrogen (BUN) and blood urea, and histopathology of hematoxylin and eosin (H&E) stained liver and kidney sections of all aforementioned groups were examined in the treated animals. Results: Nanoemulsomes of LTN-loaded GR and GL oils provided synergistic effects with LTN, exerted better ameliorative actions in reducing serum TC, LDL-C, vLDL-C, triglycerides, and AI, and improved serum HDL-C levels. Serum ALT, AST, ALP, and γ-GT levels were in the normal range for nanoemulsome groups. H&E stained liver and kidney sections of these animals confirmed better hepatoprotective and renoprotective effects than LTN alone. Serum biochemical parameters for renal functions also claimed to be in the moderate range for nanoemulsome-treated groups. Conclusion: This study demonstrated that nanoemulsomes of LTN-loaded GR and GL oils synergistically provided better antihyperlipidemic, hepatoprotective, and renoprotective effects as compared to LTN alone.

Previous studies have shown that accumulation of advanced glycation end products (AGEs) can be the cause of diabetic nephropathy (DN) in diabetic patients. Dihydrochalcone 3′-O-β-d-glucopyranosyl α,4,2′,4′,6′-pentahydroxy–dihydrochalcone (1) is a powerful antiglycation compound previously isolated from Eysenhardtia polystachya. The aim was to investigate whether (1) was able to protect against diabetic nephropathy in streptozotocin (STZ)-induced diabetic mice, which displayed renal dysfunction markers such as body weight, creatinine, uric acid, serum urea, total urinary protein, and urea nitrogen in the blood (BUN). In addition, pathological changes were evaluated including glycated hemoglobin (HbA1c), advanced glycation end products (AGEs) in the kidney, as well as in circulation level and pro-inflammatory markers ICAM-1 levels in diabetic mice. After 5 weeks, these elevated markers of dihydrochalcone treatment (25, 50 and 100 mg/kg) were significantly (p < 0.05) attenuated. In addition, they ameliorate the indices of renal inflammation as indicated by ICAM-1 markers. The kidney and circulatory AGEs levels in diabetic mice were significantly (p < 0.05) attenuated by (1) treatment. Histological analysis of kidney tissues showed an important recovery in its structure compared with the diabetic group. It was found that the compound (1) attenuated the renal damage in diabetic mice by inhibiting AGEs formation.

Ethnopharmacological relevance Portulaca oleracea L. is a widespread medicinal plant that is used not only as an edible plant, but also as a traditional medicine for alleviating a wide spectrum of diseases. It is a well-known plant in the European Traditional Medicine. PA is mentioned by Dioscorides (40–90 CE), with the name of “andrachne”. Aim of the review In this study, we provide detailed information on botany, traditional uses, phytochemistry, pharmacological uses, pharmacokinetics and safety of P. oleracea . Materials and methods An extensive search on electronic databases including PubMed, Web of Science, Google Scholar, ScienceDirect, Scopus, conference papers, local herbal encyclopedias, articles, books (in English, French, Arabic, Persian, etc .) and also a number of unpublished handwritten manuscripts was done to find articles have been published between 1956 and 2015 on pharmacology and phytochemistry of P. oleracea. Results P. oleracea has been addressed in De Materia Medica as an astringent, and a remedy for headaches, inflammation of the eyes and other organs, burning of the stomach, erysipela, disorders of the bladder, numbness of the teeth, excessive sexual desire, burning fevers, worms, dysentery, hemorrhoids, eruptions of blood, and bites. Phytochemical investigations revealed that this plant a wide range of secondary metabolites including alkaloids, terpenoids, flavonoids and organic acids. The most important pharmacological activities are renoprotective activities and effects on metabolism. P. oleracea could successfully decrease blood glucose and lipid profile of patients with metabolic syndrome. The safety of P. oleracea has been reported in many clinical trials. Conclusion Modern pharmacological studies have now proven many traditional uses of P. oleracea , including anti-hyperglycemic and anti-hyperlipidemic, renoprotective and hepatoprotective effects. In addition, in many clinical trials P. oleracea showed no adverse effects and constipation was reported as the most frequent adverse effect. [ABSTRACT FROM AUTHOR]

Background: Tropaeolum majus L. (Tropaeolaceae) is an important medicinal plant belonging to the Tropaeolaceae family, which has 80 species distributed in South and Central America. In Brazil, it is distributed practically throughout the entire territory and it is popularly known as "capuchinha". In folk medicine its leaves are widely used for treatment of cardiovascular disorders. Despite consistent data showing some acute effects on renal and cardiovascular system, no study has investigated whether Tropaeolum majus extracts is able to exert cardiorenal protective effects after 30 days of treatment, i.e. in a sustained manner. Objective: Investigate the prolonged cardiorenal protective effects of ethanolic extract obtained from Tropaeolum majus (EETM) in rats with renovascular hypertension. Material and Methods: First, EETM was obtained and chemically characterized. Then, we investigated the possible antihypertensive and diuretics effects, including effects on renal haemodynamics, after prolonged treatment (30 days) with EETM (3, 30 and 300 mg/kg). Finally, we examined whether treatment with EETM may affect the angiotensin-converting enzyme (ACE) and oxidative stress, preventing heart and kidney damage in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats. Results: Prolonged treatment with EETM was able to prevent the evolution of renovascular hypertension in 2K1C rats, inducing important renoprotective effects and reducing systemic blood pressure and cardiac hypertrophy. Moreover, it was also identified that these effects may be directly related to significant ACE inhibitory activity and reduction of oxidative stress. Conclusion: This study has brought new scientific evidence of preclinical efficacy of EETM as a cardiorenal protective agent in rats with renovascular hypertension. [ABSTRACT FROM AUTHOR]

Adenosine (ADO) is an important regulatory purine nucleoside that accumulates at sites of inflammation and tissue injury including in diseases associated with renal pathology. Endogenous levels of ADO may be increased by inhibiting the ADO-metabolizing enzyme, ADO kinase (AK). AK inhibitors have demonstrated protection in rodent models of diabetic nephropathy. To further investigate AK inhibition as a potential mechanism for renal protection, A-306989, a potent non-nucleoside AK inhibitor, was examined in both in vitro and in vivo assays of renal injury. A-306989 prevented podocyte damage (disruption of actin cytoskeleton) and increased podocyte survival following puromycin aminonucleoside (PAN) application in both mouse and human conditionally immortalized podocytes. Prophylactic oral administration of A-306989 (1.5, 5 and 15 mg/kg) reduced proteinuria in a dose-dependent manner and repressed pro-inflammatory/fibrotic gene up-regulation; A-306989 was also efficacious when administered two days following the PAN-insult. A-306989 (10 and 30 mg/kg) also significantly reduced proteinuria and macrophage infiltration in a rat model of glomerulonephritis. Finally, A-306989 (15 and 50 mg/kg) reduced the expression levels of pro-inflammatory/fibrotic genes, and reduced macrophage infiltration (50 mg/kg), but did not affect the deposition of interstitial collagen in fibrotic kidneys from mice with unilateral ureter obstruction. A-306989 also had beneficial actions on “quality of life” measures including improving body weight loss. Thus, these data indicate that enhancement of endogenous ADO levels by A-306989 can positively modulate renal pathology and mimic some of the previously reported beneficial actions of ADO A 2A receptor agonists. [ABSTRACT FROM AUTHOR]

Cassia fistula (Fabaceae) is one of the most commonly used medicinal plants for its antimalarial and antimicrobial activities. So far, safety of the plant fruit seed as a traditional medicine has not been well investigated. Therefore, the effect of C. fistula seeds on sub-chronic hepatic toxicity in chicks fed with 30-50 mg/kg methanolic extract of the fruit seeds, for 7-21 days, was investigated. The protective effect of C. fistula on organs and the hematological and biochemical parameters were examined. At 40 mg/kg dose of C. fistula to chicks showed a non-significant decrease in count of RBCs and other serological values, presumably through a provoked hemolysis of RBCs and/or toxicity of the plant. However, a significant reduction in liver function enzymes (ALP, ALT and AST) urea, and creatinine levels with an increase in plasma protein reflected on its hepato-renal protection. Only nominal pathological lesions were observed in microscopic examination of the chick's hepatic tissues. We propose that C. fistula fruit seeds are hepatoprotective and renoprotective. [ABSTRACT FROM AUTHOR]

Se estudió el efecto del ozono por vía rectal a diferentes dosis sobre variables de función renal y la presión arterial sistólica en un modelo de glomerulonefritis tóxica experimental por adriamicina. La glomerulonefritis experimental es causa de insuficiencia renal, caracterizada por un daño renal progresivo. Existen diferentes esquemas de tratamiento, los cuales son muy caros y producen inmunosupresión, que afecta la calidad de vida del paciente. Para desarrollar este trabajo se utilizaron 40 ratas hembras Wistar de 200 g de peso, divididas en 4 grupos, uno control, otro control positivo, que recibieron adriamicina durante un período de 10 semanas, y otros 2 que recibieron terapia con ozono. A todos se les determinó la proteinuria, presión arterial sistólica y diuresis de 24 h. Los resultados mostraron que la terapia con ozono a una dosis de 0,3 mg/kg tuvo efecto renoprotectorThe effect of ozone by rectal route at different doses on variables of renal function and systolic arterial pressure was studied in a model of experimental toxic glomerulonephritis due to adriamicine. Experimental glomerulonephritis causes renal failure and it is characterized by a progressive renal damage. There are different treatment schemes that are very expensive and produce immunosupression, affecting the patient’s quality of life. To develop this work, 40 Wistar rats of 200 g of weight were used. They were dividided into 4 groups: a control group and a positive control group that were administered adriamicine during 10 weeks, and other 2 that received ozone therapy. Proteinuria, systolic arterial pressure and 24-hour diuresis were determined in all of them. The results showed that ozone therapy at a dosis of 0.3 mg/kg had a renal protective effect

This study investigated the therapeutic potential of undigested goby fish ( Zosterisessor ophiocephalus ) muscle proteins (UGP) and their hydrolysates on high-fat-high-fructose diet (HFFD)-fed rats. HFFD induced hyperglycemia, manifested by a significant increase in the levels of glucose and glycogen as well as α-amylase activity when compared to normal rats. The administration of GPHs to HFFD-fed rats significantly decreased α-amylase activity and the contents of blood glucose and hepatic glycogen. By contrast, the UGP increased the glucose metabolic disorders in HFFD-fed rats. Furthermore, HFFD-fed rats showed oxidative stress, as evidenced by decreased antioxidant enzyme activities and glutathione (GSH) levels and increased concentration of the lipid peroxidation product malondialdehyde in liver and kidney. Interestingly, the daily gavage of UGP and GPHs improved the redox status in liver and kidney of HFFD-rats by ameliorating or reversing the above-mentioned changes. Moreover, GPHs exhibited a renal protective role by reversing the HFFD-induced decease of uric acid and increase of creatinine levels in serum and preventing some HFFD-induced changes in kidney architecture. The results demonstrate that GPHs contain bioactive peptides that possess significant hypoglycemic and antioxidant properties, and ameliorate renal damage in rats fed hypercaloric diet. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is associated with complications in several different systems of the body, and the incidence of diabetes is rapidly increasing worldwide. The objective of the present study was to evaluate the effect of aqueous extract of Cydonia oblonga Mill. fruit on lipid profile and some biochemical parameters in streptozotocin-induced diabetic rats. The extract showed antihyperlipidemic activity as evidenced by significant decreases in serum triglyceride, total cholesterol, and low density lipoprotein cholesterol (LDL-C) levels along with the elevation of high density lipoprotein cholesterol (HDL-C) in the diabetic rats. The biochemical liver functional tests were also analyzed and it was shown that serum biomarkers of liver dysfunction, including alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were significantly reduced in aqueous extract of Cydonia oblonga Mill. treated diabetic rats. In addition, our results showed that the oral administration of the extract prevented diabetes-induced increase in serum urea and creatinine levels as the markers of renal dysfunction. In conclusion, the present study indicates that aqueous extract of Cydonia oblonga Mill. is able to improve some of the symptoms associated with diabetes and possesses hypolipidemic, hepatoprotective, and renoprotective effects in streptozotocin-induced diabetic rats. [ABSTRACT FROM AUTHOR]

Background: Patients with resistant focal segmental glomerulosclerosis (FSGS) who are unresponsive to corticosteroids and other immunosuppressive agents are at very high risk of progression to end stage kidney disease. In the absence of curative treatment, current therapy centers on renoprotective interventions that reduce proteinuria and fibrosis. The FONT (Novel Therapies for Resistant FSGS) Phase II clinical trial (NCT00814255, Registration date December 22, 2008) was designed to assess the efficacy of adalimumab and galactose compared to standard medical therapy which was comprised of lisinopril, losartan, and atorvastatin. Methods: Key eligibility criteria were biopsy confirmed primary FSGS or documentation of a causative genetic mutation, urine protein:creatinine ratio >1.0 g/g, and estimated glomerular filtration rate (eGFR) >40 ml/min/1.73 m². The experimental treatments - adalimumab, galactose, standard medical therapy-- were administered for 26 weeks. The primary endpoint was a 50 % reduction in proteinuria with stable eGFR. Results: Thirty-two subjects were screened and 21 were assigned to one of the three study arms. While none of the adalimumab-treated subjects achieved the primary outcome, 2 subjects in the galactose and 2 in the standard medical therapy arm had a 50 % reduction in proteinuria without a decline in eGFR. The proteinuria response did not correlate with serial changes in the serum glomerular permeability activity measured by the Palb assay or soluble urokinase plasminogen activator receptor (suPAR). There were no serious adverse effects related to treatments in the study. Conclusions: Recruitment into this trial that addressed patients with resistant FSGS fell short of the enrollment goal. Our findings suggest that future studies of novel therapies for rare glomerular diseases such as FSGS may benefit from enrollment of patients earlier in the course of their disease. In addition, better identification of patients who are likely to respond to a new treatment based on biomarkers suggesting involvement of the disease pathway targeted by the experimental agent may reduce the required sample size and increase the likelihood of a favorable outcome. [ABSTRACT FROM AUTHOR]

Background: In this study, we investigated the protective effect of thymol as a natural compound against cisplatin-induced nephrotoxicity by quantitative renal 99mTc-DMSA uptake and compared its effect with histopathology in mice. Materials and methods: Mice were divided into six groups as control, cisplatin (7.5 mg/kg, intraperitoneally), thymol + cisplatin (thymol; 50 and 150 mg/kg + cisplatin; 7.5 mg/kg) and thymol (50 and 150 mg/kg). Thymol was orally administrated for two days before cisplatin injection and continued for 4 days. 99mTc-DMSA was injected through the tail of mice after the drug administration. The percentage of the injected dose per gram of kidney tissue (%ID/g) was calculated. In other experiment, kidneys of treated mice were assessed for histopathology. Results: 99mTc-DMSA uptake per gram tissue of the kidneys as %ID/g was 85.27 ± 21.81, 45.55 ± 5.50, 65.02 ± 32.21 and 88.46 ± 20.46 in the control, cisplatin, thymol (50 mg/kg) + cisplatin and thymol (150 mg/kg) + cisplatin. Thymol administration with cisplatin resulted in a significant increase in the level of %ID/g. Histopathological examinations showed a protective effect of thymol against cisplatin nephrotoxicity in mice. Conclusion: The results showed that thymol significantly attenuates the cisplatin-induced nephrotoxicity in mice, and 99mTc-DMSA uptake in kidney is a suitable method for assessment of nephrotoxicity in mice. [ABSTRACT FROM AUTHOR]

The fruiting bodies of Ganoderma lucidum have been used in China for the prevention of a wide range of diseases including diabetic nephropathy. Our current investigation with this mushroom led to the isolation of six new and two known phenolic meroterpenoids. The structures and absolute configurations at all stereogenic centers in these substances were assigned by using spectroscopic and computational methods. The new meroterpenoids, chizhines A–F ( 1 – 6 ), are isolated as racemic mixtures. Chiral HPLC was utilized to obtain the individual (−)- and (+)-antipodes of these substances. The renoprotective effects of the selected members of the series, were evaluated by using the ELISA technique and high-glucose-induced rat mesangial cells. The results show that the individual enantiomers of these substances significantly inhibit monocyte chemotactic protein 1 (MCP-1) and fibronectin production in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

The current study was designed to evaluate the hypolipidemic and renopro-tective effects of methanolic extract of powdered Canscora decussata whole plant in the diabetic rabbits. Thirty rabbits were divided into five groups having 6 animals each including normal and diabetic controls groups, the remaining groups received methanolic extract in 400 and 600 mg/kg doses and another group got pioglitazone (3 mg/kg) for 30 days. Serum levels of triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, albumin, globulin and total proteins were estimated by using commercially available kits. The results showed that extract significantly (p

Objective To determine whether people seen by the Far North Queensland Specialist Medical Outreach Service ( SMOS) with chronic kidney disease ( CKD) and proteinuria were treated according to established guidelines. Design Audit of SMOS clinical reports from 18th May to 27th July 2012. Clinical markers were compared with the Caring for Australians with Renal Impairment and National Heart Foundation management guidelines. Setting Reports covering primary health care centres located in remote communities of Cape York Peninsula and Torres Strait, Far North Queensland. Main outcome measure(s) The proportion of people with CKD and proteinuria on appropriate renoprotective treatment with an angiotensin-converting enzyme inhibitor ( ACE-inhibitor) or angiotensin-2 receptor blocker ( ARB). The proportion of people with CKD and proteinuria reaching blood pressure targets as per National Heart Foundation guidelines. The proportion of people with stage 4 CKD appropriately referred to a specialist renal service. Results One hundred and eighty-six clinical reports were reviewed; 48 people had markers of CKD. Forty-five of the 48 (94%) had been prescribed an ACE-inhibitor or ARB according to management guidelines. Nineteen of the 48 (40%) had blood pressures within the target range. Four of six people with late-stage CKD (stage 4 or 5) had been referred to a specialist renal service. Conclusions This audit confirms the high rate of CKD in the people of Far North Queensland, although this is a highly selected sample. It shows appropriate prescribing of renoprotective treatment in most cases. However, it also highlights the need for a more vigorous approach to blood pressure control. [ABSTRACT FROM AUTHOR]

The current study was designed to evaluate the hypolipidemic and renoprotective effects of methanolic extract of powdered Canscora decussata whole plant in the diabetic rabbits. Thirty rabbits were divided into five groups having 6 animals each including normal and diabetic controls groups, the remaining groups received methanolic extract in 400 and 600 mg/kg doses and another group got pioglitazone (3 mg/kg) for 30 days. Serum levels of triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, albumin, globulin and total proteins were estimated by using commercially available kits. The results showed that extract significantly (p<0.01) decreased the raised parameters including triglyceride, total cholesterol and LDL-cholesterol, atherogenic index, Coronary risk index up to normal values compared to diabetic rabbits. However, it significantly increased HDL-cholesterol, albumin, globulin and total protein levels. Therefore, it is suggested that methanolic extract of C. decussata exerts hypolipidemic and renoprotective effects in the alloxan-induced diabetic rabbits. [ABSTRACT FROM AUTHOR]

Purpose: Drug-induced nephrotoxicity is one of the most common side effects of medications and accounts for about 20 % of hospital admissions for acute kidney injury (AKI). Some possible pharmacologic mechanisms of pentoxifylline (PTX) that suggest it as a candidate to ameliorate AKI include interaction at the level of the adenosine receptors, increase in erythrocyte deformability, stimulation of vasodilatory prostaglandins production and prevention of vascular congestion, and suppression of tumor necrosis factor alpha (TNF-α) and apoptosis. This manuscript reviews all clinical and animal studies on the use of PTX as a renoprotective agent against a number of nephrotoxic drugs. Methods: Data were collected by searching MEDLINE, PubMed, Scopus, Cochrane central register of controlled trials, and Cochrane database systematic reviews. Key words used as search terms were pentoxifylline, nephroprotective, renoprotective, drug-induced renal diseases, drug-induced nephrotoxicity, drug-induced renal toxicity, and drug-induced nephropathy. This search was performed without time limitation. Results and conclusion: Most greatest number of studies and human clinical trials on the renoprotective effect of PTX against drug-induced nephrotoxicity involves cyclosporine (Cyc). It seems that despite encouraging results from animal studies, there is insufficient evidence to support the renoprotective effect of PTX against Cyc-induced nephrotoxicity in humans. Although some available animal studies show protective effects of PTX against renal toxicity of some antimicrobial and cytotoxic agents, designing clinical trials to approve these nephroprotective effects requires prior confirmation of no reducing antimicrobial or antitumor action of these medications by PTX. [ABSTRACT FROM AUTHOR]

Background Several studies have demonstrated a short-term antiproteinuric effect of mineralocorticoid receptor blockers (MRB) on proteinuric kidney diseases, but no information is available about the long-term persistence (>1 year) of such reduction in proteinuria and the long-term effects of MRB on renal function. Methods We prospectively studied the effects of adding spironolactone (25 mg/day) to 87 patients who maintained proteinuria higher than 1 g/day in spite of renin–angiotensin system blockade. The mean follow-up was 25 ± 15 (1–84) months. Results Estimated glomerular filtration rate (eGFR) showed an acute fall in the first month of treatment (5.1 ± 9.4 mL/min/1.73 m2), but it remained stable thereafter (+0.04 ± 0.7 mL/min/1.73 m2/month), with a significant difference with respect to the eGFR slope during the 12-month pre-treatment period. The initial eGFR fall predicted a more stable course of renal function, the higher the eGFR initial fall, the better the long-term evolution of eGFR. Proteinuria showed an important and sustained reduction since the first month of treatment. At the end of follow-up, it had decreased by 61% (43–77%) with respect to baseline values. The antiproteinuric and renoprotective influence of spironolactone was also observed in diabetic patients and in patients with renal function impairment, although tolerance was poorer among the latter. Conclusions Spironolactone induces an initial acute fall in eGFR that predicts a later favourable influence on the course of renal function and a remarkable and sustained reduction in proteinuria. [ABSTRACT FROM AUTHOR]

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.

Objective: Aged garlic extract (AGE) has been proven to exhibit antioxidant, hypolipidemic, hypoglycemic and antidiabetic properties. However, its effect on diabetic nephropathy was unexplored. Therefore, the present study was designed to investigate the renoprotective effect of AGE in streptozotocin-induced diabetic rats. Materials and Methods: Albino Wistar rats were induced with diabetes by a single intraperitoneal injection of 45 mg/kg b.w. of streptozotocin. Commercially available AGE was supplemented orally at a dose of 500 mg/kg body weight/day. Aminoguanidine, which has been proven to be an anti-glycation agent was used as positive control and was supplemented at a dose of 1 g/L in drinking water. The serum and urinary biochemical parameters were analyzed in all the groups and at the end of 12 weeks follow up, the renal histological examination were performed using H & E and PAS staining. Results: The diabetic rats showed a significant change in the urine (P < 0.001) and serum (P < 0.01) constituents such as albumin, creatinine, urea nitrogen and glycated hemoglobin. In addition, the serum lipid profile of the diabetic rats were altered significantly (P < 0.05) compared to that of the control rats. However, the diabetic rats supplemented with aged garlic extract restored all these biochemical changes. The efficacy of the extract was substantiated by the histopathological changes in the kidney. Conclusion: From our results, we conclude that aged garlic extract has the ability to ameliorate kidney damage in diabetic rats and the renoprotective effect of AGE may be attributed to its anti-glycation and hypolipidemic activities. [ABSTRACT FROM AUTHOR]

Abstract: Deferoxamine (DFO) is a recognized iron chelator which has been shown to exert nephroprotection in models of toxic nephropathies. In the present work the potential protective effects of DFO against Cr(VI)-induced nephrotoxicity and oxidant stress were evaluated. Rats were injected with a single injection (15mg/kg, s.c.) of potassium dichromate (K2Cr2O7). DFO was given as a single i.p. injection 30min before K2Cr2O7 administration at three different doses (100, 200 and 400mg/kg). It was found that DFO pretreatment attenuated, in a dose-dependent way, K2Cr2O7-induced renal dysfunction and structural alterations evaluated by serum creatinine, blood urea nitrogen, creatinine clearance, proteinuria, plasma glutathione peroxidase activity, urinary excretion of N-acetyl-β-d-glucosaminidase and histological analyses. Furthermore, DFO prevented the K2Cr2O7-induced renal oxidant stress and the decrease in the activity of the antioxidant enzymes superoxide dismutase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase and catalase. Finally it was found that DFO, at 400mg/kg, decreases renal Cr(VI) content which prompted us to evaluate the potential Cr(VI) chelating properties of this compound. Indeed was found in an in vitro assay that DFO was an effective Cr(VI) chelator with an IC50 of 800μg. In additional groups of rats was found that DFO posttreatment was ineffective to attenuate K2Cr2O7-induced nephrotoxicity and renal oxidant stress. Furthermore, DFO was unable to modify urinary excretion of total chromium. The nephroprotective effect of DFO against Cr(VI)-induced nephrotoxicity and oxidant stress may be explained, at least partially, by the ability of DFO to chelate Cr(VI) and to attenuate renal Cr(VI) content. However, it cannot be excluded that the ability of DFO to chelate iron may also be involved in the protection observed in our study. [Copyright &y& Elsevier]

Abstract: Ethanolic extract of Ficus racemosa [FRE] was subjected to bioactivity guided fractionation by steady state and kinetic methods using nanosecond pulse radiolysis and stopped-flow spectrophotometer. HPLC fingerprinting and other antioxidant studies revealed that quantitative difference in FRE and its fractions were insignificant. Hence FRE was chosen for the evaluation of renoprotective study in mice using ischemia/reperfusion injury. Pretreatment of FRE (50 and 100mg/kg) restored the serum biomarkers and tissue antioxidant status to near normal levels, which were altered in ischemic group. Further, HPLC studies revealed that FRE contains gallic acid (6.18mg/g) as major constituent and it is responsible for observed beneficial effects. [Copyright &y& Elsevier]

Phytotherapy is the traditional method used to cure many diseases. Various medicinal plants found in many parts of India are well known for their various medicinal values. The Terminalia chebula Retz. a native plant of Asia is found to have various properties like anti-oxidant and free radical scavenging activity, anti-carcinogenic activity, ant-imutagenic activity, anti-bacterial activity, anti-fungal activity, anti-viral activity, anti-diabetic, renoprotective activity, cardio-protective activity, anti-inflammatory and anti-arthritic activity. These properties of T. chebula discussed in this review are mainly due to the presence of various types of phytoconstituents. [ABSTRACT FROM AUTHOR]

Cilnidipine, an L-/N-type calcium channel blocker, dilates the efferent glomerular arterioles in an experimental model and shows a renoprotective effect, but its clinical benefits and safety have not yet been assessed in type II diabetics with albuminuria. The objective of this trial was to evaluate the effect of reducing albuminuria in type II diabetic patients with a combination therapy consisting of valsartan plus cilnidipine versus monotherapy with valsartan. An open-label, randomized controlled trial was conducted from April 2002 to October 2003 in 87 Japanese patients aged 31–90 years with type II diabetes showing albuminuria (urinary albumin/creatinine ratio: 10–300 mg/g). The patients were randomized to receive either valsartan (n=41) or valsartan plus cilnidipine (n=46) once daily for 1 year. The primary end point was the percent change in the albumin/creatinine ratio. The secondary end points were the progression/regression of albuminuria, blood pressure (BP), renal function, and safety. After 1 year, the albumin/creatinine ratio was found to have decreased more markedly in the valsartan plus cilnidipine group than in the valsartan group (reduction rate −44±11% (s.e.) versus −9±7% (s.e.); P=0.014 by analysis of covariance). Although a significant reduction was observed in the systolic and diastolic BP of both groups from baseline to 1 year (P<0.0001, respectively), there was no significant difference in the change in the BP between the two groups (systolic BP, P=0.066; diastolic BP, P=0.391). There were also no significant differences in the side effects between the two groups. Cilnidipine was thus found to show an additive effect with valsartan and thereby caused a reduction in albuminuria in type II diabetics.Kidney International (2006) 70, 151–156. doi:10.1038/sj.ki.5000349; published online 17 May 2006 [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. [ABSTRACT FROM AUTHOR]