Preventive Effect of ZnO-Metformin Nanocomposite Against Carbon Tetrachloride-Induced Hepatotoxicity

Objective(s): The protective effect of metformin on liver disorders has been reported . Studies have documented the hepatoprotective benefits of metformin against liver disorders, but due to its low bioavailability and untoward side effects, metformin has limited therapeutic utility. Nanotechnology has increased efficiency and reduced the side effects of several drugs. Methods: A ZnO-metformin nanocomposite was synthesized. The protective effects of metformin (150 mg/kg), ZnO (10 mg/kg), and the ZnO-metformin nanocomposite (50, 100, 150 mg/kg) were compared in a CCl4-induced hepatocellular damaged mouse model. Serum liver enzymes, oxidative stress biomarkers, and histological changes in hepatocytes were evaluated. Results: The levels of AST, ALT and ALP in the blood were prevented by the metformin and ZnO-metformin nanocomposite against the action of CCl4, as well as liver damage associated with it. Furthermore, metformin or/and ZnO-metformin nanocomposite reversed the SOD, GPx and GR activity that was found to be lowered due to CCl4, as well as increased MDA levels under the same condition. The extent of hepatoprotection with respect to the two agents in question also differed significantly in terms of dose. The ZnO-metformin nanocomposite hepatoprotective effects occurred at lower doses than metformin.  ZnO alone did not alter the CCl4-induced hepatic injury. Conclusions: The ZnO-metformin nanocomposite was a more efficient hepatoprotective agent at lower doses than metformin. The ZnO-metformin nanocomposite has the potential to be a replacement for metformin as a hepatoprotective drug candidate.