Evaluation of Hepatoprotective Effect of Omega-3 Fatty Acids on Isotretinoin-induced Liver Injury in Albino Rats

Abstract

Isotretinoin is a very effective retinoid, commonly used in the management of severe acne. However, its use may be accompanied by hepatic and metabolic disturbances, including changes in liver function, dyslipidemia, oxidative stress, and inflammation. Omega-3 fatty acids have well-documented anti-inflammatory, antioxidant, and lipid-modulating properties and therefore may represent a hepatoprotective intervention for drug-induced liver injury. This study was conducted to evaluate the hepatoprotective effects of omega-3 against isotretinoin-induced liver injury in albino rats. Twenty-eight albino rats were randomly assigned to 4 groups: control, omega-3 alone (300 mg/kg), isotretinoin alone (40 mg/kg), and combined isotretinoin plus omega-3. All treatments were administered orally for 21 consecutive days, and the vehicle used was 10% corn oil. Liver function was assessed by measuring ALT, AST, ALP, GGT, total bilirubin, albumin, and total protein. Lipid metabolism was measured by total cholesterol, triglycerides, LDL-c and HDL-c. Inflammatory status was evaluated using CRP and IL-6, and oxidative stress and antioxidant status using MDA, GSH, and SOD. Histopathological examination of liver tissue was also performed. Compared with the control group, isotretinoin administration resulted in significant body-weight loss and an increased liver index, accompanied by significant elevations in ALT, AST, ALP, GGT, and total bilirubin, as well as reductions in albumin and total protein levels. Isotretinoin also caused significant dyslipidemia with an increase in total cholesterol, triglycerides, and LDL-c, and a decrease in HDL-c. In addition, isotretinoin significantly increased CRP, IL-6, and MDA levels but decreased GSH and SOD activities, suggesting an increased inflammatory and oxidative stress response. These biochemical changes correlated with significant histopathological evidence of hepatic injury. Nevertheless, the co-administration of omega-3 significantly attenuated the isotretinoin-induced alterations by improving hepatic function and lipid profile, decreasing systemic and hepatic inflammation, increasing antioxidant defenses, and preserving hepatic architecture. Omega-3 had a significant hepatoprotective effect against isotretinoin-induced liver injury in albino rats. These findings suggest that omega-3 may be used as an adjuvant approach to attenuated isotretinoin-induced hepatotoxicity and require further investigation in long-term experimental and clinical studies.