Pirfenidone attenuates nonalcoholic fatty liver disease through activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway

Nonalcoholic fatty liver disease (NAFLD) originates from the hepatopathy of fatty liver. Pirfenidone is a novel broad-spectrum anti-fibrosis agent used for treating various kinds of tissue fibrosis. The present study will evaluate the effects of Pirfenidone on liver injury in high-fat diet (HFD)-fed mice to evaluate the value of Pirfenidone in treating NAFLD. The pathology of NAFLD was simulated by feeding mice with an HFD in the present study, followed by treating the HFD mice with 150 and 300 mg/kg/day Pirfenidone once a day. The pathological state of HFD mice was identified by the elevated liver weight, promoted serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels, declined serum high-density lipoprotein cholesterol (HDL-C) levels, increased alanine aminotransferase and aspartate aminotransferase activity, and histopathological changes to the liver tissues, all of which were dramatically ameliorated by 150 and 300 mg/kg Pirfenidone administration. Furthermore, the excessive production of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6, as well as upregulated phosphorylated nuclear factor kappa-B (p- NF-kappa B p65), were observed in HFD-fed mice, but significantly reversed by Pirfenidone. Finally, activated oxidative stress, identified by promoted malondialdehyde (MDA) levels and declined catalase (CAT) activity, was observed in HFD-fed mice, accompanied by the downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and sterol-regulatory element-binding proteins-1c (SREBP-1c). After the treatment with Pirfenidone, oxidative stress was greatly mitigated. Our results imply that Pirfenidone ameliorated the progression of NAFLD by mediating inflammation and oxidative stress.

Automated summary

This study evaluated the effects of Pirfenidone on liver injury in high-fat diet-fed mice and found that Pirfenidone can ameliorate the progression of nonalcoholic fatty liver disease (NAFLD) by mediating inflammation and oxidative stress.