Exposure to environmental level phenanthrene induces a NASH-like phenotype in new born rat

Abstract More and more evidence indicates that persistent organic pollutants (POPs) are a risk factor for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Phenanthrene (Phe) is a kind of POP which existed extensively in the environment, but whose toxicity on mammals has so far received less focus. Subcutaneously injection of Phe (0.5, 5, 50 μg/kg) for 21 days induced significant NAFLD/NASH symptoms in new born rats. Exposure to environmental levels of Phe decreased body weight and liver-somatic index; impaired histology of liver; influenced the peroxisome proliferator-activated receptor gamma (PPARγ) signaling and lipid metabolism in liver; stimulated oxidative stress in the rats' liver; induced the variation of NFκB pathway and liver inflammatory response; and caused liver fibrosis via transforming growth factor β1 ( tgfβ1 ). We speculated that the subcutaneously injected Phe was transferred to the liver through blood circulation, which may have induced the elevation of PPARγ directly or indirectly, leading to liver steatosis. Excess lipid, acting as the first hit, stimulated the second hit factors - oxidative stress, inflammatory response and lipid peroxidation, and finally resulted in steatohepatitis and liver fibrosis.