The impact of glucagon and exenatide on oxidative stress levels and antioxidative enzyme expression in in vitro induced steatosis in HepG2 cell culture

Abstract

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a healthcare issue of growing concern. Its development is multifactorial, and it is more commonly seen in obese patients. In those circumstances, intracellular lipid overload ensues, resulting in oxidative stress that might be responsible for progression toward steatohepatitis. Novel therapeutic approaches that are effective in weight management are expected to improve the course of MASLD. One of the potential mechanisms involved in such protective properties may relate to the reduction in oxidative stress.

Material and methods: The induction of steatosis and the assessment of oxidative stress level and expression of antioxidant enzymes (superoxide dismutase — SOD, glutathione peroxidase — GPx and catalase — Cat) in HepG2 hepatoma cell line subjected to glucagon and exenatide treatment.

Results: Exenatide monotherapy successfully reduced lipid accumulation by 25%. Significant reductions in markers of oxidative stress (reactive oxygen species and malondialdehyde) were obtained in cells subjected to combined treatment with glucagon and exenatide (by 24 and 21%, respectively). Reduced burden of oxidative stress was associated with elevated expression of SOD and GPx but not Cat.

Conclusions: Combined activation of glucagon-like peptide-1 (GLP-1) and glucagon receptors reduces oxidative stress in HepG2 steatotic cell cultures. This observation may stem from increased antioxidative potential.