Protective effect of selenium on gentamicin-induced oxidative stress and nephrotoxicity in rats

Abstract

Gentamicin (GM) is a widely used antibiotic against serious, life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of selenium (Se) in GM-induced nephrotoxicity in rats. Experiments were done on 32 adult Wistar rats divided into four groups of 8 animals each. The GM group received gentamicin (100 mg/kg), whereas the GM+Se group received the same dose of GM and selenium (1 mg/kg) by intraperitoneal (i.p.) injections on a daily basis. Animals in the Se group, serving as a positive control, received only selenium (1 mg/kg) and the control group received saline (1 mL/day), both given i.p. All groups were treated during 8 consecutive days. Quantitative evaluation of GM-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of selenium coadministration with GM. GM was observed to cause a severe nephrotoxicity, which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous selenium administration protected kidney tissue against oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by selenium pretreatment. The results from our study indicate that selenium supplementation attenuates oxidative-stress-associated renal injury by reducing oxygen free radicals and lipid peroxidation in GM-treated rats.

Modulatory effects of dietary inclusion of garlic (Allium sativum) on gentamycin–induced hepatotoxicity and oxidative stress in rats

“…Also, a highly significant decrease SOD and catalase activity was reported in this study, these observations are in agreement with those of, Yaman and Balikci [23] . Reduced glutathione act as an intracellular free radical scavengers and protect cells against radical mediated lipid peroxidation [26] .…”

“…(Randjelovic et al, 2012) limits its therapeutic usefulness. Garlic has been shown to possess profound antioxidants properties (Lawal et al, 2011) and its use in this study to ameliorate the hepatotoxic and oxidative effects of gentamycin is instructive.…”

Sigma S-Dependent Antioxidant Defense Protects Stationary-Phase Escherichia coli against the Bactericidal Antibiotic Gentamicin

“…Thus, in mice, this drug significantly increases kidney myeloperoxidase activity, lipid peroxidation, and protein carbonylation. It has been shown that the resulting acute renal failure is caused by ROS, and the use of M40403, which is a low-molecular-weight mimetic of superoxide dismutase, attenuates this damage (64,65,75). Similarly, proteomic analysis implicates Gmmediated oxidative stress in Leishmania since the proteins affected by drug exposure included the thiol-redox control system (76).…”

“…We interpret this to show that, at higher concentrations, the ability of Gm to disrupt protein synthesis is strong enough not to be affected by the defective antioxidant defense of the mutant, but at a low concentration, the drug relies also on the added effect of oxidative stress to be effective. A strong enough attack on elements of the E. coli antioxidant defense, for example, by small-molecule inhibitors of the proteins identified above, should therefore enhance Gm effectiveness in combating this disease and permit the use of lower drug concentrations, thereby minimizing drug side effects such as nephrotoxicity (64,65).…”

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.…”