Hepatoprotective potential of lamivudine through activation of gamma-glutamyltransferase and down-regulation of p53 in HepG2 cells

Abstract

The liver is a crucial metabolic organ that aids in detoxification, produces energy, synthesizes essential proteins, and is essential for maintaining good health. Since hepatocytes are the main type of cell found in liver tissue, maintaining their safety is essential for the general health of livers. The hepato-protective qualities of lamivudine shield the liver from stressful situations. The current study aimed to assess lamivudine's protective effects on HepG2 cells subjected to ethanol damage. Lamivudine was given to HepG2 cells after they were cultivated and subjected to ethanol-induced damage. Cell viability was assessed using the MTT, Crystal Violet, and Trypan Blue tests. The results of the MTT experiment demonstrated that lamivudine administration improved the rate of cell viability in a dose-dependent manner at 25, 50, and 100 μg/mL (0.570±0.0205; 0.73 ±0.02; 0.897±0.0206, respectively). According to the Crystal Violet test, lamivμdine-treated cells had higher cell viability than untreated cells; the rates were around 0.38 ± 0.01, 0.516 ± 0.0305, and 0.656 ± 0.041 in a dose dependant manner. The Trypan Blue assay results also confirmed that treatment with lamivudine at 25 μg/mL, 50 μg/mL, and 100 μg/mL led to a increase in the viability of cells compared to the injury group (183.66±5.50; 151±3.61; 115±5, respectively). Pretreatment of HepG2 cells with lamivudine during 100 µg/mL concentration exposure resulted in near-normalization of p53 expression levels (24.73±0.60), GSH levels (28.83±1.16), and in hepatic activity levels of GGT (21.23±1.12) compared to control. In immunofluorescence microscopy, the 100 µg/mL lamivudine group showed the most significant reduction in fluorescence intensity. Lamivudine provided convenient features in protecting HepG2 cells against ethanol-triggered liver damage by enhancing cell survival and antioxidant enzyme activities.