Long-term exposure of triclosan (TCS), an important antimicrobial agent, can lead to deleterious effects on liver growth and development. However, the related mechanisms on TCS-induced hepatocyte injury remain unclear. Herein, we found that after long-time TCS exposure to adult zebrafish (Danio rerio) from 6 hpf (hours post-fertilization) to 90 dpf (days post-fertilization), the body weight and hepatic weight were significantly increased in concomitant with a large amount of lipid droplet accumulation in liver. Also, TCS exposure resulted in occurrence of oxidative stress by increasing the concentrations of malondialdehyde and reducing the activity of superoxide dismutase both in zebrafish larvae (120 hpf) and adult liver. By H&E staining, we observed a series of abnormal phenomena such as severely hepatocellular atrophy and necrosis, as well as prominently increased hepatic plate gap in TCS-exposure treatment groups. Through AO staining, TCS induced obvious apoptosis in larval heart and liver; through TUNEL assay, a concentration-dependent apoptosis was found to mainly occur in adult liver and its surrounding tissues. The mRNA and protein expression of anti-apoptotic protein Bcl-2 decreased, while that of pro-apoptosis protein Bax significantly increased, identifying that liver injury was closely related to hepatocyte apoptosis. The significant up-regulation of MAPK and p53 at both mRNA and protein levels proved that TCS-induced hepatocyte apoptosis was closely related to activating the MAPK/p53 signaling pathway. These results strongly suggest that long-term TCS-exposure may pose a great injury to zebrafish liver development by means of activating MAPK/p53 apoptotic signaling pathway, also lay theoretical foundation for further assessing TCS-induced ecological healthy risk.
Keywords: Bax; Bcl-2; Hepatocyte apoptosis; Liver injury; MAPK/p53 signaling pathway; Triclosan exposure.
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