Protective effect of Panax ginseng on AlCl₃-induced liver, kidney, and testis toxicity in male albino rats: biochemical, histopathological, and molecular study

Abstract

Aluminum chloride (AlCl₃) is a ubiquitous environmental toxicant that induces multi-organ toxicity, primarily via oxidative stress and inflammatory mechanism cascades. Panax ginseng, renowned for its pharmacologically active ginsenosides, exhibited potent antioxidant and anti-inflammatory activities. Accordingly, this study aimed to evaluate the protective effects of Panax ginseng extract against AlCl₃-induced liver, kidneys, and testes damage, with a specific focus on the expression of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) as a potential mediator. Forty-five male albino rats (Rattus norvegicus), weighing 155.80 g ± 0.52 g at 82 days of age, were randomly assigned into three experimental groups (n = 15 in each): control group (CG); AlCl₃-treated group (AlCl₃ group), which received 300 mg/kg body weight/day of AlCl₃·6H₂O via oral gavage daily for 28 days; and co-treatment group (AlCl₃/P-G), 300 mg/kg body weight/day of AlCl₃·6H₂O concurrently with 250 mg/kg/BW Panax ginseng for 28 days. This study integrated three analytical pillars: biochemical profiling of serum lipids and liver/kidney function markers alongside SIRT1 protein assessment using ELISA; histopathological evaluation of hepatic, renal, and testicular tissues utilizing H&E staining; and qPCR analysis of SIRT1 mRNA expression. The AlCl₃/P-G group demonstrated weight improvement on days 21 and 28 of treatment compared to AlCl₃ and CG groups. It exhibited significantly lower lipid profile values than AlCl₃ (p < 0.01). Panax ginseng treatment in this group led to improved creatinine, urea, ALT, and AST levels compared to AlCl₃, along with a significant increase in serum SIRT1 protein concentration and hepatic SIRT1 mRNA expression (0.70-fold of CG levels) compared AlCl₃ (0.50-fold). The treatment also partially restored renal architecture with compact glomeruli and reduced tubular degeneration, as well as hepatic architecture showing reduced swelling and less congestion. Testis sections in the AlCl₃/P-G group showed recovery in epithelial organization and increased spermatogenic activity; however, causal mechanisms remain to be established. In conclusion, Panax ginseng may have protective effect on AlCl₃-induced liver, kidney, and testicular toxicity.