Mitigating Chloramphenicol induced liver toxicity by exploring the therapeutic potential of Astaxanthin and Quercetin.

This study investigates the efficacy of Astaxanthin and Quercetin as potential therapeutic agents for mitigating chloramphenicol-induced liver toxicity. Despite chloramphenicol's broad-spectrum antibiotic properties, its clinical utility is hampered by hepatotoxic side effects. This research assesses the impact of chloramphenicol-induced mitochondrial toxicity, reactive oxygen species (ROS) production, and gene expression alterations in HepG2 liver cells. To enhance mitochondrial sensitivity, cells were cultured in galactose-containing media and exposed to chloramphenicol (up to 3000 µmol/L) for 48 h, with or without Astaxanthin (5-15 µM) or Quercetin (10-30 µM). Untreated and DMSO vehicle controls were included. Mitochondrial toxicity was evaluated using ATP content, ROS levels (ROS-Glo™ assay), and gene expression profiling. Expression of five mitochondrial-related genes SOD2, UCP2, NRF1, SURF1, and TFAM were analyzed due to their roles in oxidative stress, membrane potential regulation, biogenesis, and respiratory complex assembly. Antioxidant treatments resulted in significant reductions in ROS levels (p < 0.005) and restoration of mitochondrial gene expression patterns (p < 0.05, n = 3), alongside improved ATP retention. IC50 values and statistical comparisons were derived using GraphPad Prism with one-way ANOVA and appropriate post hoc tests. These findings suggest that Astaxanthin and Quercetin confer mitochondrial protection through modulation of oxidative stress and gene expression.