Evaluation of in vitro hepatotoxic effects of monoamine oxidase inhibitor drugs

Monoamine oxidase (MAO) inhibitors have been used for many years in the treatment of depression, panic disease and social phobia. Despite the long-term use of these drugs, the hepatotoxic effect profiles and mechanisms of these effects in terms of liver damage are still not fully elucidated; however, MAO inhibitors are reported to be at high risk for drug-induced liver injury (DILI). From this point; The aim of this thesis is to evaluate hepatotoxicity of MAO inhibitor drugs Moclobemide, Selegiline and Chlorgiline on HepG2 cell lines. For this purpose, cytotoxic effects of agents by 3- (4,5-dimethyl-2-thiazolyl) -2,5-diphenyl tetrazolium bromide (MTT) method, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and total bilirubin (TBILI) levels, biomarkers of possible toxicity, determination of apoptotic/necrotic cell death, oxidative stress parameters were determined; possible hepatotoxicity and mechanisms were evaluated. As a result, chlorgiline induced cytotoxicity and apoptosis and increased ALT, AST and urea levels. Selegiline decreased ALT, AST and urea levels. All drugs induced apoptotic processes and oxidative stress; however, moclobemide led to significant reactive oxygen species (ROS) increase compared to positive control. When all the results were evaluated, chlorgiline caused significant differences in the markers of more hepatotoxicity than other agents. As a result, in this study, hepatotoxicity monitoring of MAO inhibitors was performed and a new follow-up method for DILI, which can be difficult to detect in the preclinical period but the results can be destructive, has been proposed.