Protective Effects of Nanocurcumin and Fenofibrate on Diet-Induced Nonalcoholic Steatohepatitis in Rats: A Study on Modulation of Oxidative Stress

Abstract

Background: If not adequately treated, non-alcoholic fatty liver disease (NAFLD) may progressively worsen, eventually leading to cirrhosis and hepatocellular carcinoma. Emerging evidence suggests that fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, along with curcumin-derived formulations, may hold therapeutic potential in managing NAFLD. Objectives: This research was conducted to assess the liver-protective properties of nanocurcumin and fenofibrate using a high-fat diet (HFD)-induced rat model of NAFLD. Methods: Male Wistar rats, aged 7 - 8 weeks, were fed a HFD for eight weeks to establish a model of NAFLD. The rats were subsequently allocated into five distinct experimental groups: Normal control, HFD control, HFD plus fenofibrate, HFD plus curcumin, and HFD plus nanocurcumin. Liver histopathology, serum liver enzymes, and lipid profiles were evaluated. Hepatic expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase isoforms, antioxidant enzymes, PPARα, and lipid metabolism-related genes was also analyzed. Results: In the NAFLD model rats, treatment with fenofibrate and nanocurcumin resulted in a significant reduction in the expression of sterol regulatory element-binding protein 1c (SREBP1c), PPARα, NADPH oxidase isoforms, and levels of reactive oxygen species (ROS). Additionally, both treatments significantly upregulated the expression of PPARα and carnitine palmitoyl transferase 1 alpha. Serum levels of liver enzymes and lipid profiles were significantly improved following drug treatment compared to the HFD control group. Conclusions: Our results demonstrate that fenofibrate and nanocurcumin effectively ameliorate non-alcoholic steatohepatitis (NASH) by modulating key factors involved in lipid metabolism, inflammation, and oxidative stress (OS). These findings suggest that nanocurcumin, as a natural compound with enhanced bioactivity, may provide therapeutic benefits comparable to fenofibrate in the management of NASH.