Semaglutide Mitigates Doxorubicin-Induced Hepatic and Renal Damage: Functional, Anti-Inflammatory, and Histopathological Insights

Objective: This research was intended to elucidate the nephroprotective and hepatoprotective effects of semaglutide against doxorubicin-induced toxicity. Methods: Thirty-five female rats were allocated and classified into 5 groups: Negative control: distilled water for the period of seven days. The next group of rats, known as the positive control, was treated with only distilled water in addition to only one dose of doxorubicin (12 mg/kg) on the 7th day. Low dose of semaglutide (SL), moderate dose of semaglutide (SM), and high dose of semaglutide (SH). All semaglutide groups received treatment for the duration of 7 days and a single dose of doxorubicin on the 7th day. On the 8th day, all the animals underwent euthanization, and samples of blood were collected for the purpose of measuring liver enzymes, ADH, urea, creatinine, hs-CRP, TNF-α, IL-10, and CBC. Liver and kidney tissues were submitted for histopathological analysis. Results: Semaglutide groups significantly reduced serum creatinine and blood urea, with a maximum reduction observed in the SH group. The SH group significantly attenuated hs-CRP and TNF-α. All doses of semaglutide significantly elevated the level of IL-10 and ameliorated the granulocyte-to-lymphocyte and platelet-to-lymphocyte ratios compared to the positive control. The microscopical analysis by a histopathologic expert supports the biochemical results as well. Conclusions: Semaglutide possesses hepatic and renoprotective effects via attenuating the biomarkers of liver and kidney damage along with anti-inflammatory activity, with the maximum effects offered by the highest dose of semaglutide.