Abstract
Environmental pollutants, including polychlorinated biphenyls (PCBs), act as endocrine disruptors and impair various physiological processes. PCB 126 is associated with steatohepatitis, fibrosis, cirrhosis, and other hepatic injuries. These disorders can be regulated by microRNAs (miRNAs). Therefore, this study aimed to investigate the role of miRNAs in non-alcoholic fatty liver disease associated with exposure to PCB 126. Adult male C57BL/6 mice were exposed to PCB 126 (5 μmol/kg of body weight) for 10 weeks. The PCB group showed lipid accumulation in the liver in the presence of macro- and microvesicular steatosis and fibrosis with increased inflammatory and profibrotic gene expression, consistent with non-alcoholic steatohepatitis (NASH). PCB exposure also upregulated miR-155 and miR-34a, which induce the expression of proinflammatory cytokines and inflammation in the liver and reduce the expression of peroxisome proliferator-activated receptor α, which, in turn, impairs lipid oxidation and hepatic steatosis. Therefore, the present study showed that PCB 126 induced NASH via potential mechanisms involving miR-155 and miR-34a, which may contribute to the development of new diagnostic markers and therapeutic strategies.
Funder
Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Publisher
Public Library of Science (PLoS)
Reference48 articles.
1. The effects of PCB126 on intra-hepatic mechanisms associated with non alcoholic fatty liver disease;M-P Boucher;J Diabetes Metab Disord,2015
2. Identification of lipidomic markers of chronic 3,3’,4,4’,5-pentachlorobiphenyl (PCB 126) exposure in the male rat liver;I Kania-Korwel;Toxicology,2017
3. Acute toxicity of 3,3’,4,4’,5-pentachlorobiphenyl (PCB 126) in male Sprague-Dawley rats: effects on hepatic oxidative stress, glutathione and metals status;I Lai;Environ Int,2010
4. Environmental occurrence, abundance, and potential toxicity of polychlorinated biphenyl congeners: considerations for a congener-specific analysis;VA McFarland;Environ Health Perspect,1989
5. Polychlorinated Biphenyls, Lead, and Mercury Are Associated with Liver Disease in American Adults: NHANES 2003–2004;M Cave;Environ Health Perspect,2010