Garlic Alleviates the Injurious Impact of Cyclosporine-A in Male Rats through Modulation of Fibrogenic and Steroidogenic Genes

SIMPLE SUMMARY: The use of garlic extract is a conventional approach in improving the side effects induced by cyclosporine A (CsA) and in maintaining health. The current study explored the impact of garlic on liver and testicular function, blood biochemical parameters, and oxidative stress in rats raised under cyclosporine A toxicity. It was found that the administration of garlic restored liver function and modulated lipid markers. Garlic supplementation improved the gene expression of Superoxide dismutase (SOD) and steroidogenesis genes, decreased that of collagen I-α1 (Col1a1) and transforming growth factor-1β (TGF-β1), and enhanced the antioxidant status and fertility. A combined treatment of garlic and CsA is advocated to alleviate CsA-induced oxidative stress injuries and other adverse effects. ABSTRACT: This work aimed to study the hepato-testicular protective effect of garlic in rats treated with cyclosporine A (CsA). Forty male Westar albino rats were randomly distributed in five groups (8 rats each): control, olive oil, garlic, CsA, and CsA co-treated with garlic. CsA induced an upsurge in the alanine transaminase, aspartate transaminase, and alkaline phosphatase levels and decreased albumin and total protein levels, expression of superoxide dismutase (SOD) gene, serum testosterone, triiodothyronine, and thyroxine levels compared to the control group. Additionally, there was an increase in the cholesterol, triglyceride, and low-density lipoprotein levels and a substantial reduction in the high-density lipoprotein levels compared to the control groups. Histopathological investigation of the liver showed abnormalities like hepatic cell degeneration, congestion of blood vessels, and highly active Kupffer cells in the CsA group. Histopathological examination of testes showed damaged seminiferous tubules, stoppage of the maturation of spermatogonia, and the presence of cells with irregular dense nuclei in the lumina of some tubules. For the groups treated with garlic, mitigation of the damage caused by CsA in the liver and testes, liver function tests, lipid profiles, and hormones was seen along with improved gene expression of SOD and steroidogenesis genes, and decreased gene expression of collagen I-α1 and transforming growth factor-1β. Conclusively, garlic had a positive impact on CsA-induced hepatic and sperm toxicity. It is recommended that garlic should be supplemented in transplant treatments using CsA to alleviate the cyclosporin-induced oxidative injuries and other harmful effects.