Study on the Role and Mechanism of HDAC6 in Cd-Induced Inflammation and Fibrosis in Mice Liver

The heavy metal cadmium (Cd) is one of the major environmental pollution toxicants, which is highly toxic to the environment and can cause damages to many organs after entering human body. Studies have shown that Cd pollution is characterized by long-cycle and insidiousness, and long-term Cd exposure can lead to liver fibrosis, but the mechanism remains unclear. This study employed a Cd-induced liver fibrosis mouse model to investigate the health effects for toxic of Cd exposure by oral administration on inflammation and fibrosis of the liver, and to further explore the role and mechanism of histone deacetylase 6 (HDAC6) in this model. Results showed that the Cd exposure induced inflammation and fibrosis of mice’s liver. Based on Western blotting and immunofluorescence analysis, we found that the expression of HDAC6 was significantly up-regulated after Cd exposure. Cd also triggered multiple signal media-tors of endoplasmic reticulum (ER) stress including activating transcription factor-6 (ATF-6), double-stranded RNA-activated protein kinase-like ER kinase (PERK), and inositol-requiring enzyme-1 (IRE-1) pathway, as well as GRP78 protein in the liver. Oral administration of 23BB significantly improved ER stress-related liver inflammation and fibrosis. In summary, inhibition of HDAC6 modulated inflammation and fibrosis via the inactivation of ER stress in Cd-induced liver damage. Our findings provide new insights into the health effects of the liver damage induced by Cd exposure, highlighting that HDAC6 may be a potential target for therapy against Cd-induced inflammation and fibrosis in the liver.