Antioxidant Effect of the Aerial Part of <i>P. granatum:</i> Exploring the Protective and Restorative Effect in Gentamycin and Cisplatin-Induced Hepatorenal Toxicity in Rat Models

Aim: The present study aimed to explore the hepatorenal efficacy of ethanolic and hydroalcoholic extract against Gentamicin and Cisplatin-induced toxicity in experimental rats. Background: The current research focuses on the characterization and evaluation of the hepatorenal efficacy of P. granatum extracts on cellular and tissue models, particularly in terms of its restorative actions following cytotoxic damage induced by Gentamicin and Cisplatin. This work builds upon several key areas of contemporary scientific research. Objective: The objective of the current investigation was to establish an association of oxidative stress in hepatorenal insufficiency caused by Gentamicin and Cisplatin xenobiotics and its amelioration with the antioxidant activity of ethanolic extract of Punica granatum (EEPG) and hydroalcoholic extract of Punica granatum (HAEPG). Methods: Using ascorbic acid as a standard, the in vitro antioxidant activity of EEPG and HAEPG was assessed using the DPPH method. The hepatorenal efficiency of the EEPG and HAEPG were studied in Gentamicin and Cisplatin-induced models. The hepatorenal toxicity was induced by 100 mg/kg/day i.p. of Gentamicin for 12 days and 1.5 mg/kg/day i.p. cisplatin for 3 weeks in Wistar albino rats. Lipid profile, serum hepatorenal markers, and hepatorenal tissue oxidative markers such as, CAT, MDA, GSH, and SOD were estimated to assess the extent of hepatorenal efficiency. Using Masson trichrome (MT) stained tissue sections, renal and hepatic tissue damage was assessed. The degree of renal tissue damage was evaluated using tubular necrosis, perivascular edema, intratubular proteinaceous cast, and vascular congestion. Results: In vitro studies have shown that the HAEPG containing higher total phenolic and flavonoid content, exhibits greater antioxidant activity compared to the EEPG. The severity of hepatotoxicity and renal toxicity was found to be more severe in cisplatin than Gentamicin. The Cisplatin treatment more severely affects the level of CAT, GSH, and SOD, respectively compared to Gentamicin induction. Cisplatin also significantly decreased SOD and increased MDA levels. Treatment with EEPG and HAEPG demonstrated beneficial effects by reducing the levels of oxidative enzymes, which contributes to the restoration of hepatorenal damage due to their antioxidant properties. The MT panels of the treated groups revealed and supported hepatorenal regenerative changes. Conclusion: The antioxidant properties of EEPG and HAEPG showed beneficial effects and ameliorated the levels of tissue hepatorenal oxidative enzymes and were found to possess restoration of hepatorenal damage in a dose-dependent manner.