Amleorative Role of Esculetin􀇧mediated Renoprotection Against Gentamicin􀇧induced Nephrotoxicity and Possible Involvement of N􀇧methyl􀇧d􀇧aspartate Receptors

Abstract

Objective: In this investigation, the amleorative role of esculetin (Esc) was investigated in gentamicin (Genta) nephrotoxicity in rats and the possible role of N-methyl-D-aspartate receptors (NMDAR) in genta-induced nephrotoxicity.Methods: Genta (100 mg/kg/day, i.p. for 7 days) was administered to rats for the induction of nephrotoxicity, and subsequently, the extent of renal damage was measured by estimating creatinine clearance (CrCl), blood urea nitrogen (BUN), uric acid, microprotienuria and fractional excretion of sodium, and potassium. In addition, renal superoxide anion generation (SAG), Thiobarbituric acid reactive substance (TBARS), and reduced glutathione (GSH) level were used to evaluate renal oxidative parameters. Renal myeloperoxidase (MPO) activity was used to measure renal inflammation. D-serine, NMDA agonist was used in this study to evaluate the role of NMDA antagonist in genta-induced nephrotoxicity. Histopathological examination was performed using hematoxylin and eosin staining method.Results: Genta-treated rats exhibited remarkable changes in renal parameters like increase in BUN, uric acid, microprotein fractional excretion of sodium and potassium with decrease in CrCl and similarly biochemical parameters like increase in SAG, thiobarbituric acid reactive species (TBARS), MPO activity with decrease in GSH level. Treatment with Esc (5 and 10 mg/kg/day, i.p for 7 days), NMDAR antagonist attenuated the genta-induced nephrotoxicity but did not shown significant effect on combined use of genta and D-serine treated group. Histopathological examination of gentatreated rats. The coadministration of Esc + genta-protected kidney tissue from nephrotoxic effect of genta as illustrated by normalization of tubules but not with the combined use of Esc + genta + D-serine treated rats.Conclusion: Esc displayed protective effect in genta-induced nephrotoxicity but combined effect of Esc + genta + D-serine abolished the protective effect of Esc thus confirming that NMDAR may be involved in genta-induced nephrotoxicity.

Antioxidant and Anti-Inflammatory Effects of Curcumin Contribute Into Attenuation of Acute Gentamicin-Induced Nephrotoxicity in Rats

“…Nephrotoxicity is a renal-specific condition in which the flow of toxic metabolites does not go resourcefully due to toxic agents and drugs. Approximately 20% of nephrotoxicity is caused by drugs; this fraction is augmented in the elderly due to the rise in the life span [1].…”

“…Chronic and high dose of gentamicin provokes in vitro and in vivo free radical productions and induction of oxidative stress. Gentamicin triggers mitochondrial superoxide anions causing generation of hydroxyl radicals [1]. Moreover, antioxidant agents demonstrate a renoprotective effect in gentamicin-induced nephrotoxicity.…”

Pomegranate Attenuates Acute Gentamicin-Induced Nephrotoxicity in Sprague-Dawley Rats: The Potential Antioxidant and Anti-Inflammatory Effects

“…Nephrotoxicity is a renal-specific circumstance due to toxic agents and drugs. About 20% of nephrotoxicity is induced and caused by drugs; this fraction is augmented in the old age due to ascend in the life span [1].…”