Protective Effects of Insulin-Like Growth Factor (IGF-1) in Doxorubicininduced Experimental Liver and Kidney Injury

Abstract

Purpose: This study aimed to investigate the protective effects of insulin-like growth factor-1 (IGF-1) against doxorubicin (DOX)-induced liver and kidney damage in rats using biochemical, immunohistochemical, and histopathological methods. Materials and Methods: A total of 32 Wistar albino rats were randomly assigned into four groups: Control, DOX (4 mg/kg/week), IGF-1 (1 mu g/kg daily), and DOX + IGF-1 (DOX 4 mg/kg/week + IGF-1 1 mu g/kg daily). After the four-week experimental protocol, blood, liver, and kidney tissues were collected under anesthesia. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), urea, and creatinine were analyzed biochemically. Total antioxidant status (TAS) and total oxidant status (TOS) in liver and kidney tissues were measured using ELISA. Gene expression levels of HIF-1 alpha and iNOS were evaluated by real-time PCR. Histopathological and immunohistochemical (Caspase-3, TNF-alpha, and FGF-2) evaluations were conducted on liver and kidney tissues. Results: DOX significantly increased serum ALT, AST, BUN, urea, and creatinine levels and elevated TOS while reducing TAS in tissues). HIF-1 alpha expression was markedly upregulated (+5.50-fold), indicating oxidative damage. IGF-1 administration reduced serum ALT, AST, BUN, urea, and creatinine levels, increased TAS, and decreased TOS. Expression levels of HIF-1 alpha and iNOS approached those of the control group. DOX caused significant histopathological damage and increased Caspase-3 and TNF-alpha expressions in the liver and Caspase-3 and FGF-2 expressions in the kidney. These alterations were ameliorated by IGF-1 treatment. Conclusion: The findings suggest that IGF-1 exerts protective effects against DOX-induced hepatorenal toxicity, possibly through its antioxidant, antiinflammatory, and anti-apoptotic properties.