Adverse effects of chronic exposure to nonylphenol on non-alcoholic fatty liver disease in male rats

PLoS One. 2017 Jul 7;12(7):e0180218. doi: 10.1371/journal.pone.0180218. eCollection 2017.


Endocrine-disrupting chemical (EDC) has been thought to play a role in non-alcoholic fatty liver disease (NAFLD). However, the toxic effects of Nonylphenol (NP), an EDC, on non-alcoholic fatty liver disease have never been elaborated. This study aimed to investigate whether exposure to NP could induce NAFDL, a promoting effect of high-sucrose-high-fat diet (HSHFD) on the adverse effects caused by NP was evaluated. Fourth eight male rats were assigned to four groups and each group was treated with a specific testing sample: normal-diet (ND) control group (C-ND); normal diet plus NP (180mg/kg/day) group (NP-ND); high-sucrose-high-fat-diet control group (C-HSHFD); HSHFD plus NP (180mg/kg/day) group (NP-HSHFD). At the age of 80 day, sonogram presents diffusely increased hepatic echogenicity in the NP-HSHFD group. The oblique diameter of liver in the NP-HSHFD group was significantly bigger than that in both the C-ND and NP-ND groups. At the age of 90 day, exposure to NP-HSHFD and NP-ND caused a significant increase in NP concentration in liver as compared to the C-ND group. The rats in the groups treated with NP+ND, HSHFD and NP+HSHFD produced significant increases in the body weight, fat weight and FMI, respectively, when compared to the C-ND group. The liver weight and hepatosomatic indexes (HIS) of rats in the NP-HSHFD group are higher than those in the C-HSHFD group. Exposure to NP-HSHFD induced the increases in plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) as compared to the C-ND group. Morphological examination of liver tissue from rats exposed to NP+HSHFD shown steatosis with marked accumulation of lipid droplets, hepatocellular ballooning degeneration and inflammatory cell infiltration. Chronic exposure to NP might induce NAFLD in male rats. The high-sucrose-high-fat diet accelerates and exacerbates the development of NAFLD caused by NP exposure.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Cholesterol / blood
  • Diet, High-Fat
  • Humans
  • Lipid Droplets / drug effects
  • Liver / diagnostic imaging
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Non-alcoholic Fatty Liver Disease / blood
  • Non-alcoholic Fatty Liver Disease / chemically induced
  • Non-alcoholic Fatty Liver Disease / diagnostic imaging*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Phenols / blood
  • Phenols / toxicity*
  • Rats
  • Triglycerides / blood


  • Phenols
  • Triglycerides
  • nonylphenol
  • Cholesterol
  • Aspartate Aminotransferases
  • Alanine Transaminase

Grant support

This work was supported by the foundation of the National Natural Science Foundation of China (81360439); Fund of Department of Science and Technology of Guizhou Province, China (LH[2014]7543, LH[2015]7521); Youth Foundation of Department of Education of Guizhou Province (KY[2013]198); Bidding project of Zunyi Medical University of China (2013F-68, 2016F-784); 2015 Fund for key discipline construction in Zunyi Medical University (No.0996034); Scientific and Technological Fund of Department of Health of Guizhou Province, China (Fund No. gzwkj20131127); Excellent Youth Science and Technique Talents of Guizhou Province ([2016]5612).