Taurine protected As2O3-induced the activation of hepatic stellate cells through inhibiting PPARα-autophagy pathway

The activation of hepatic stellate cells (HSCs) is a key event in the development of hepatic fibrosis caused by arsenic. However, it is unclear how arsenic induces the activation of HSCs. In the present study, we found that arsenic trioxide (As2O3) induced liver tissue damage, stimulated autophagy and HSCs activation, and increased collagen accumulation in the liver of mice. Supplemented with taurine (Tau) attenuated the changes mentioned above caused by As2O3. In human hepatic stellate cell line LX-2 cells, we found that As2O3-induced activation of HSCs was autophagy-dependent, and we found that peroxisome proliferator activated receptors alpha (PPAR alpha) played an important role in arsenic-induced HSCs activation. In addition, inhibiting autophagy and PPAR alpha alleviated the activation of HSCs and lipid droplet loss induced by As2O3. Moreover, we found that Tau alleviated As2O3-induced elevation of autophagy and PPAR alpha expression, and activation of the HSCs. Our results indicated that autophagy was regulated by PPAR alpha and was involved in lipid droplet loss during the activation of HSCs. Tau alleviated As2O3 induced HSCs activation by inhibiting the PPAR alpha/autophagy pathway. These findings give an innovative insight into the association of PPAR alpha, autophagy, the activation of HSCs and hepatic fibrosis induced by As2O3.