Narrow Results

The pathogenesis of gentamicin (GM) nephrotoxicity has been shown to involve the generation of oxygen free radicals, and several free radical scavengers have been shown to ameliorate the nephrotoxicity. The seeds and oil of Nigella sativa are reported to possess strong antioxidant properties and was effective against disease and chemically-induced hepatotoxicity and nephrotoxicity. Therefore, in the present work, we have tested whether oral treatment of rats with N. sativa oil (0.5, 1.0 or 2.0 ml/kg/day for 10 days) would ameliorate nephrotoxicity of GM (80 mg/kg/day given intramuscularly and concomitantly with the oil during the last 6 days of treatment). Nephrotoxicity was evaluated histopathologically with a light microscope and by measurement of concentrations of urea, creatinine and total antioxidant status (TAS) in plasma and reduced glutathione (GSH) and TAS in kidney cortex. The results indicated that GM treatment caused moderate proximal tubular damage, significantly increased the concentrations of creatinine and urea, and decreased that of TAS and GSH. Treatment with N. sativa oil produced a dose-dependent amelioration of the biochemical and histological indices of GM nephrotoxicity that was statistically significant at the two higher doses used. Compared to controls, treatment of rats with N. sativa did not cause any overt toxicity, and it increased GSH and TAS concentrations in renal cortex and enhanced growth. The results suggest that N. sativa may be useful in ameliorating signs of GM nephrotoxicity in rats, and pending further experimentation to determine safety and efficacy, may be useful clinically.

Schisandrin B (Sch B) is an active ingredient of the fruit of Schisandra chinensis. It has many therapeutic effects arising from its tonic, sedative, antitussive and antiaging activities and is also used in the treatment of viral and chemical hepatitis. The aim of this study was to investigate the protective effects of Sch B on cyclosporine A (CsA)-induced nephrotoxicity in mice and HK-2 cells (a human proximal tubular epithelial cell line). After gavage with Sch B (20 mg/kg) or olive oil (vehicle), mice received CsA (30 mg/kg) by subcutaneous injection once daily for four weeks. Renal function, histopathology, and tissue glutathione (GSH) and malondialdehyde (MDA) levels were evaluated after the last treatment. The effects of Sch B on CsA–induced oxidative damage in HK-2 cells were investigated by measuring cell viability, the release of lactate dehydrogenase (LDH), the level of reactive oxygen species (ROS), and the cellular GSH and ATP concentrations. Cellular apoptosis was assessed by flow cytometry. Treatment with Sch B in CsA-treated mice significantly suppressed the elevation of blood urea nitrogen (BUN) and serum creatinine levels and attenuated the histopathological changes. Additionally, Sch B also decreased renal MDA levels and increased GSH levels in CsA-treated mice. Using an in vitro model, Sch B (2.5, 5 and 10 μM) significantly increased the cell viability and reduced LDH release and apoptosis induced by CsA (10 μM) in HK-2 cells. Furthermore, Sch B increased the intracellular GSH and ATP levels and attenuated CsA-induced ROS generation. In conclusion, Sch B appears to protect against CsA-induced nephrotoxicity by decreasing oxidative stress and cell death.

Hemidesmus indicus (HI) is used in ancient Indian traditional herbal medicine to treat hepatic and renal disorders. The present study was designed to investigate the protective effect of HI aqueous extract against bromobenzene induced mitochondrial dysfunction in rat kidneys. Rats were administered bromobenzene with or without prior administration of HI or vitamin E. At the end of the experiment animals were sacrificed and kidneys were obtained to study mitochondrial function, oxidative stress parameters and histopathology. Administration of bromobenzene caused significant changes like: decrease in the mitochondrial respiration and P/O ratios, increase in lipid peroxidation and protein oxidation, and decrease in the activities of antioxidant enzymes (catalase, glutathione reductase, glutathione peroxidase and superoxide dismutase) in mitochondria with significant histopathological changes in the kidney. Prior administration of HI extract showed a significant protection against bromobenzene induced changes in the kidney and this effect is attributed to the antioxidant and free radical scavenging potential of the HI. The protection was much better with HI compared to vitamin E.

This study examined whether serotonin and two of its derivatives, $N$-feruloylserotonin and $N$-($p$-coumaroyl) serotonin, have a renoprotective effect in a mouse model of cisplatin-induced acute renal failure. Cisplatin (20mg/kg body weight) was administered by intraperitoneal injection to male BALB/c mice that had received oral serotonin, $N$-feruloylserotonin or $N$-($p$-coumaroyl) serotonin (7.5mg/kg body weight per day) during the preceding 2 days. At 3 days after the cisplatin injection, serum and renal biochemical factors, oxidative stress, inflammation and apoptosis-related protein expression were evaluated, and histological examinations were performed. Cisplatin caused reduction in body weight and an increase in kidney weight; however, $N$-($p$-coumaroyl) serotonin and $N$-feruloylserotonin attenuated these effects. Moreover, the serotonin derivatives significantly decreased serum urea nitrogen and creatinine levels. They also significantly reduced the level of reactive oxygen species and upregulated the expression of glutathione peroxidase in the kidney. Furthermore, the serotonin derivatives improved the abnormal expression of mitogen-activated protein kinases activation-dependent inflammation- and apoptosis-related protein and caused less renal damage. These results provide important evidence that $N$-($p$-coumaroyl) serotonin and $N$-feruloylserotonin exert a pleiotropic effect on several parameters related to oxidative stress, inflammation and apoptosis. The derivatives also have a renoprotective effect in cisplatin-treated mice; however, this effect is higher with $N$-($p$-coumaroyl) serotonin.

Ginkgolic acids (GAs) are distinctive secondary metabolites of Ginkgo biloba (G. biloba) primarily found in its leaves and seeds, with the highest concentration located in the exotesta. GAs are classified as long-chain phenolic compounds, and exhibit structural similarities to lignoceric acid. Their structural diversity arises from variations in the length of side chains and their number of double bonds, resulting in six distinct forms within G. biloba extracts (GBE). Of these, GA (C15:1) is the most prevalent. As inhibitors of SUMOylation, GAs demonstrate significant antitumor activity, and can exert antineoplastic effects through multiple pathways, which positions them as potentially promising therapeutic agents for cancer treatment. Additionally, GAs exhibit notable anti-inflammatory, antibacterial, and antiviral properties, highlighting their multifaceted medicinal potential. Although the pharmacological properties of GAs have been extensively investigated, the associated risks of liver and kidney damage must not be overlooked. GAs can induce significant hepatic damage by promoting cellular apoptosis, oxidative stress, and the disruption of various metabolic processes. Furthermore, a limited number of studies have indicated that GAs may exhibit nephrotoxicity, as well as adverse effects on the skin and nervous system. Due to their recognized toxicity, the concentration of GAs is typically regulated to within 5ppm in the standardized G. biloba leaf extract EGb 761. Currently, there is no definitive evidence supporting the mutagenic toxicity of GAs. This review primarily synthesizes recent advancements in understanding the pharmacological and toxicological effects of GAs, along with their underlying mechanisms. It is anticipated that this review will stimulate scholarly discourse and elicit valuable insights.