Potential Cytoprotective Activity of some Natural and Synthetic Compound(s) against Chemically- Induced Injury in Human Hepatocytes

Abstract

Natural compounds are now considered as a corner stone in prevention and treatment of various diseases caused by liver injury and oxidative stress. Resveratrol, its analog Pterostilbene and the synthetic compound Didox are known as simple antioxidants also showing anti-inflammatory effect to protect against liver damage. Pretreatment of HepG2 cells with the tested drugs (Resveratrol, Pterostilbene and Didox) in concentrations of (10, 100 and 1000 µg/ml) and the standard drug Silymarin in the concentration of 100 µg/ml prior to CCl4 challenge, protected against CCl4-induced liver injury in a concentration-dependent manner except for Didox (10 µg/ml) and Pterostilbene (1000 µg/ml) who showed no significant difference than CCl4-challenged group. ALT and AST levels were assessed as an indication of hepatocyte membrane integrity. Furthermore, GSH, SOD, CAT and MDA were measured to asses oxidative stress level in liver cells. TNF-α, IL-1β and IL-6 were also measured as an indication of inflammation. As evidenced, tested drugs in addition to the standard drug Silymarin, showed a significant decrease in the activity of the medium enzymes ALT and AST. They also showed significant anti-lipid peroxidation, antioxidant and anti-inflammatory effects in vitro as evidenced in the significant decrease of MDA, TNF-α, IL-1β and IL-6 and the significant increase in the antioxidants; CAT,SOD and GSH. In conclusion, this study proved that Resveratrol’s analog “Pterostilbene” has showed the best pattern of antioxidant and anti-inflammatory effects on CCl4 – challenged HepG2 cells. This could be explained partly by maintaining hepatic cell integrity, alleviating oxidative stress resulting in a hepatoprotective effect of the drug against acute toxicity induced by CCl4.