Evalutai̇on of the effects of hesperi̇di̇n on li̇ver damage due to isotretinoin used in the treatment of acne vulgaris

Systemic isotretinoin used in the treatment of acne vulgaris causes liver damage, a common side effect. In this study, we evaluated the reduction of liver damage side effects developing in acne vulgaris treatment by hesperidin, which has been shown to have hepatoprotective capacity in the liver. HEPG2 cells were used as an in vitro liver model. Four groups were formed: control, hesperidin, isotretinoin, and hesperidin+isotretinoin combination group. The antioxidant activity of hesperidin was investigated using TAS analyses. Liver damage was assessed by TGF-β quantification, TGF-β expression level and aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured by RT-PCR, ER stress levels were assessed by RT-PCR, GRP78 and CHOP expression levels, and apoptosis effects were assessed by Caspase-3 and Bcl2 expression levels. As a result, total antioxidant capacity was calculated as 0.5667 mmol Trolox Equivalent/L in the control group and 0.3767 mmol Trolox Equivalent/L in the combination group. The decrease observed in the combination group compared to the control was not statistically significant (p = 0.0834). In the analysis of TGF-β levels, a fibrosis marker, the protein level was 7.333 pg/mg in the control group and 9.000 pg/mg in the combination group. The decrease in the combination group compared to the isotretinoin group was considered statistically significant (p = 0.0378). Caspase-3 mRNA expression levels were found to be decreased 0.736-fold in the control group and 0.176-fold in the combination group compared to the control group. Comparison of mRNA expression findings of genes related to ER stress, apoptosis, and fibrosis with RT-PCR and fibrosis-related TGF-β levels suggests that hesperidin has a hepatoprotective effect.