Objective: Oxidative stress is interrelated with liver diseases and contributes in the progression of non-alcoholic fatty liver disease (NAFLD). The objective of the present study was to investigate the plasma levels of oxidative stress markers and the activity of antioxidant enzymes in NAFLD and healthy subjects. Furthermore, the interaction behaviors of malondialdehyde (MDA) with Cu/Zn superoxide dismutase (SOD1) enzyme were elucidated by molecular docking.

 Methods: The study involved 60 patients with NAFLD and 16 healthy volunteers. The plasma levels of MDA, nitric oxide (NO) metabolite, ferric reducing antioxidant power (FRAP), total thiol (tSH), glutathione peroxidase (GPx) and SOD were determined.

Results: NAFLD patients had significantly higher alanine aminotransferase, MDA and NO metabolites values than the control group (p=0.007, p=0.030, p=0.030). The levels of tSH and SOD activity were significantly lower in NAFLD group as compared to control subjects (p=0.000), but no significant difference for aspartate aminotransferase, FRAP and GPx. Based on the molecular docking, MDA could establish three hydrogen bonds with key residues including Arg143 and His63 and Cu (II) in the catalytic site of SOD1 enzyme which provides data of the MDA potential to deactivate the enzymatic activity of SOD1.

Conclusion: Impaired antioxidant defense systems may be the main factor in the progression of NAFLD. Thus on the basis of our molecular docking studies, we hypothesize that the exposure to MDA has potential inhibitory action to SOD1. This study provides direct evidence at a molecular level to explain that MDA may exert its oxidant activity by specific action within the specific molecular pathway.

 

Key words: Non-alcoholic fatty liver disease; Superoxide dismutase; Malondialdehyde; Oxidative stress; Molecular docking.