Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
Mitochondrial Fatty Acid Oxidation (mtFAO) plays an important role in hepatic energy metabolism and severe mtFAO injury leads to fatty liver and liver failure. In fact, several drugs withdrawn due to safety issues are reported to induce fatty liver caused by mtFAO disruption. For example, an antibacterial Triclocarban (TCC), which was reported as an environmental pollutant and withdrawn from the market because of unknown safety in humans, induced fatty liver in rats and accumulation of lipid droplets in human hepatic LO2 cells. On the other hand, it has been reported that TTC promoted hepatic FAO in mice. Therefore, no consistent conclusions were indicated about the effect of TCC on FAO and accumulation of lipid droplets. In this study, we evaluated the mitochondrial respiratory chain in HepaRG cells to investigate the direct effect of TCC on mtFAO and lipid droplet accumulation. We also measured the expression of antioxidant genes (GCLM, HMOX1, p62, NRF2).
The results showed that a significant decrease in mtFAO and an increase in the fluorescence intensity of lipid droplets was observed after TCC treatment. We also observed a drastic increase in the expression of antioxidant genes following TCC treatment, while currently used antibiotics Etionamide and Protionamide had no such effect.
These results suggest that TCC increases oxidative stress through accumulation of lipid droplets via mtFAO inhibition in HepaRG cells. Assessment of mtFAO will enable the selection of compounds with less mitochondrial toxicity in the early stages of drug discovery.
