مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
The Role of Bilirubin in Preventing Ethanol-Induced Oxidative Damage: An In Silico and In Vitro Investigation
The Role of Bilirubin in Preventing Ethanol-Induced Oxidative Damage: An In Silico and In Vitro Investigation
Elnaz Gordani,1Amir Nili-Ahmadabadi,2,*
1. Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, IranDepartment of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran 2. Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
Introduction: Alcohol consumption is one of the effective factors in the liver toxicity. Bilirubin is produced as a fat-soluble compound during heme metabolism and is excreted from the body after conjugation with glucuronic acid. While bilirubin was previously regarded as a waste compound for many years, recent evidence suggests it can prevent oxidative damage. In this study, after conducting docking studies to investigate the interference of bilirubin on enzymes involved in ethanol metabolism, the protective effect of bilirubin on cellular toxicity induced by ethanol was investigated.
Methods: In this study, HepG2 cell survival, cell membrane integrity, and changes of lipid peroxidation (LPO)/ total antioxidant capacity (TAC) activity were evaluated following incubation of HepG2 cells with ethanol (equal IC50) and different concentrations of bilirubin. In addition, molecular docking studies on the interference of bilirubin with alcohol dehydrogenase and aldehyde dehydrogenase enzymes were investigated.
Results: Our findings showed that bilirubin can increase the survival of HepG2 cells when exposed to ethanol. The bilirubin alongside ethanol significantly decreased the LPO level and improved TAC and cell membrane integrity in HepG2 cell line. Molecular docking findings showed that bilirubin effects on the ethanol toxicity maybe related to its chemical interference with the structure of the alcohol dehydrogenase and aldehyde dehydrogenase enzymes molecule.
Conclusion: These findings demonstrate that the administration of bilirubin effectively prevents the occurrence of oxidative damage induced by ethanol. These beneficial effects might be attributed to the interaction of bilirubin with enzymes involved in ethanol metabolism.