Effect of exogenous IGF-1 administration on acetaminophen toxicity induced liver injury

IGF-1 protects against liver injury

Abstract

For liver toxicity, there is no clear protective drug till date. Here, we investigated the protective effects of insulin-like growth factor 1 (IGF-1) on acetaminophen (APAP)-induced liver injury and the molecular processes underlying APAP induced liver damage involving oxidative stress and endoplasmic reticulum (ER) stress. Forty male Wistar rats were randomly divided into four groups. Group I that had only saline served as the control. Group II received APAP (300 mg/kg body wt.) and saline, Group III & IV received APAP as in Gr. II, plus 1 and 2 mg/kg/day of IGF-1, respectively for three days. Liver histopathology, biochemical analysis and ELISA assays were performed to evaluate the protective effect of IGF 1 against APAP-induced liver injury. Significant cellular damage and necrosis were observed in the liver in the APAP and saline groups. Treatment with IGF-1 resulted in a dose-dependent reduction in cellular damage and necrosis. ALT levels, indicative of liver damage, were significantly decreased in the IGF-1-treated groups. MDA levels, a marker of oxidative stress, were reduced with IGF-1 treatment. GSH levels, an antioxidant, increased with IGF-1 treatment. ATF6 levels were reduced with IGF-1 treatment, while TNF-alpha levels were decreased in a dose-dependent manner. IGF-1 treatment protects against APAP-induced liver injury by reducing cellular damage, oxidative stress and ER stress markers. These findings suggest that IGF-1 may have therapeutic potential in mitigating APAP-induced hepatotoxicity.