Melatonin attenuates gentamicin-induced nephrotoxicity and oxidative stress in rats

Abstract

The present study investigated the protective effects of melatonin (MT) against gentamicin (GM)-induced nephrotoxicity and oxidative stress in rats. We also investigated the effects of MT on induction of apoptotic cell death and its potential mechanisms in renal tissues in response to GM treatment. The following four experimental groups were evaluated: (1) vehicle control, (2) MT (15 mg/kg/day), (3) GM (100 mg/kg/day), and (4) GM&MT. GM caused severe nephrotoxicity as evidenced by increased serum blood urea nitrogen and creatinine levels, increased renal tubular cell apoptosis, and increased Bcl2-associated X protein and cleaved caspase-3 protein expression. Additionally, GM treatment caused an increase in levels of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) protein expression in renal tissues. The significant decreases in glutathione content, catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase activities and the increase in malondialdehyde content indicated that GM-induced tissue injury was mediated through oxidative reactions. In contrast, MT treatment protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by the GM treatment. Histopathological studies confirmed the renoprotective effect of MT. These results indicate that MT prevents nephrotoxicity induced by GM in rats, presumably because it is a potent antioxidant, restores antioxidant enzyme activity, and blocks NF-κB and iNOS activation in rat kidney.

Prospects of N-Acetylcysteine and Melatonin as Treatments for Tramadol-Induced Renal Toxicity in Albino Rats

“…In conjunction with findings in the current study, authors have reported the ameliorative effect of NAC in human and animal models of drug associated renal toxicity .52-55 Also, MT have been reported to mitigate various forms of xenobioticinduced renal toxicity in animal models. [56][57][58][59][60] The observed decreases in serum levels of creatinine, urea and uric acid in MT and NAC pretreated rats could be attributed to their inhibitory effects on free radical-induced kidney damage and renal vasoconstriction. Studies have shown that treatment with NAC ameliorate decline in glomerular filtration rate and stabilized plasma creatinine by reducing vasoconstriction.…”

Comparison of the Protective Effects of Melatonin and Silymarin Against Gentamicin-Induced Nephrotoxicity in Rats

“…In addition, melatonin can inhibit the catalytic activity of nitric oxide synthase (NOS) and expression of inducible nitric oxide synthase (iNOS) at the transcriptional level that reduces the amount of NO produced. 27 Besides direct scavenger activity, melatonin can stimulate gene expression and activities of several antioxidative enzymes including GRd, GPX, CAT, and SOD, and this indirect antioxidant activity of melatonin is related to its interaction with either membrane or nuclear receptors. These antioxidative enzymes can metabolize free radicals to less reactive species and thereby decrease the formation of highly toxic by-products.…”

Gingerol Fraction from Zingiber officinale Protects against Gentamicin-Induced Nephrotoxicity

“…proximal tubular cells as the possible mechanism through which gingerol and other antioxidant substances ameliorate GM-induced nephrotoxicity. Other substances with antioxidant properties have been tested in aminoglycoside-induced nephrotoxicity (42)(43)(44). In the present study, we used a model that approximates clinical practice: an in vivo study, protective substance administration initiated after the use of the toxic agent, and evaluation of functional parameters with clinical relevance (e.g., CL CR ), in addition to histopathology, inflammatory gene expression, and oxidative status.…”