Acid sphingomyelinase mediates the noise‐induced liver disorder in mice

Autor: Yi-Bin Guo, Hong-Zhe Ma, Yu-Ting Su, Xi Zhang, Xincheng Liu, Zhenghui Gu, Xiao-Ping Xie, Jun-Xiang Bao, Yao-Ping Cheng, Yao-Ming Chang, Xing-Xing Meng
Rok vydání: 2019
Předmět:
Zdroj: Clinical and Experimental Pharmacology and Physiology. 46:556-566
ISSN: 1440-1681
0305-1870
DOI: 10.1111/1440-1681.13083
Popis: Noise-induced structural and functional disorder of the liver has been realized, but the underlying mechanism remains to be characterized, which has limited the introduction of precautious measures. Over-activation of acid sphingomyelinase (ASM)/ceramide (Cer) pathway takes centre stage in hepatocyte injury entailed by various stimulus. We aimed to investigate whether it mediated the noise elicited liver disorder on infrastructure, lipid metabolism, apoptosis, and oxidative stress. Mice were exposed to broad band noise (20-20k Hz, 90-110 dB) for 1, 3, 5 or 7 days by 3 hr/d. Doxepin hydrochloride (DOX), an ASM inhibitor was given by 5 mg/kg/d gavage. We showed that 5 or 7 days intense, broad band noise exposure caused significant infrastructure derangement and lipid droplets storage in hepatocytes. The content of cholesterol, free fatty acids or triglyceride was increased significantly in liver tissue upon noise stimulation. Moreover, the noise promoted apoptosis and superoxide generation in hepatocytes significantly, enhancing activity of aspartate aminotransferase (AST) or alanine amino transferase (ALT) in serum. Acid sphingomyelinase activity and Cer generation in liver tissue were elevated by noise exposure, which was normalized with DOX administrated. Accordingly, DOX alleviated steatosis, apoptosis, oxidative stress and enzymatic change in hepatocytes or serum of noise exposed mice substantially. In summary, our results suggest the ASM/Cer pathway contributes to the broad band noise elicited liver damage in mice.
Databáze: OpenAIRE
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