Assessment of gentamicin and cisplatin-induced kidney damage mediated via necrotic and apoptosis genes in albino rats

Abstract

Background Gentamicin (GM) is a low-cost, low-resistance antibiotic commonly used to treat gram-negative bacterial diseases. Cisplatin (Csp) is a platinum-derived anti-neoplastic agent. This experiment aimed to identify the early signs of gentamicin and cisplatin-induced nephrotoxicity in rats. Thirty Wistar rats were divided into three groups of 10: a control group, which received no treatment; a gentamicin group administered by a dose of (100 mg/kg, IP) for 7 consecutive days, and a cisplatin group was administered intraperitoneal in a dose of (1.5 mg/kg body weight) repeated twice a week for 3 weeks. Results Both experimental groups exhibited increased levels of creatinine, urea, and uric acid, with the cisplatin-treated group showing higher levels than the gentamicin group. Experimental groups also exhibited significantly increased Malondialdehyde (MDA), reduced glutathione (GSH), and glutathione peroxidase (GSH-Px) with more pronounced effects in the cisplatin-treated group. Further, both experimental groups exhibited significant up-regulation of Tumor Necrosis Factor α (TNF-α), caspase-3, and Bax and down regulation of Bcl-2. Conclusion These findings confirm the use of necrotic, apoptotic genes as early biomarkers in the detection of tubular kidney damage. Further, cisplatin was shown to have a greater nephrotoxic effect than gentamicin; therefore, its use should be constrained accordingly when co-administered with gentamicin.

Antioxidant and anti-apoptotic roles of sesame oil and N acetylcysteine against gentamicin-induced nephrotoxicity in rats

“…In this study, GM upregulated Bax and TNF-α, and downregulated Bcl-2 expression. Similar findings confirmed the same effects of GM administration (Abouzed et al 2021). SO, and/or NAC addition with GM restored Bax, Bcl-2 and TNF-α towards control group.…”

“…The proteins Bax and Bcl-2 play important roles, with Bax acting as a pro-apoptotic factor and Bcl-2 acting as an antiapoptotic factor. Furthermore, TNF-α activation causes oxidative stress and renal inflammation (Abouzed et al 2021). In this study, GM upregulated Bax and TNF-α, and downregulated Bcl-2 expression.…”

“…This study confirmed the significance of oxidative stress in nephrotoxicity evoked by GM. These points are connected between nephrotoxicity, oxidative stress, lipid peroxidation, and kidney damage (Abouzed et al 2021). These studies discovered a relationship between GM-induced nephrotoxicity and poor GSH activity in the renal cortex, which could contribute to oxidative damage due to impaired antioxidant defenses.…”

“…These studies discovered a relationship between GM-induced nephrotoxicity and poor GSH activity in the renal cortex, which could contribute to oxidative damage due to impaired antioxidant defenses. SOD inactivation would thus render it incapable of defending against the elevated ROS levels caused by GM (Abouzed et al 2021). GM accumulates in the renal tubules, lowering antioxidant defenses, and causing tubular necrosis, glomerular congestion, and kidney failure (Abdel-Raheem et al 2009).…”

Chemical Composition and Valorization of Broccoli Leaf By-Products (Brassica oleracea L. Variety: Italica) to Ameliorate Reno-Hepatic Toxicity Induced by Gentamicin in Rats

“…Several studies have demonstrated the molecular mechanism by which GTN induce renal injury. This is seen to include renal tubular damage leading to necrosis and glomerular congestion, subsequently causing renal dysfunction [8]. Furthermore, reports show that GTN increases serum liver enzymes and induces histological lesions, reflecting its hepatotoxic effects.…”