Protective effect of crocin on BPA-induced liver toxicity in rats through inhibition of oxidative stress and downregulation of MAPK and MAPKAP signaling pathway and miRNA-122 expression

Food Chem Toxicol. 2017 Sep;107(Pt A):395-405. doi: 10.1016/j.fct.2017.07.007. Epub 2017 Jul 6.


Bisphenol A (BPA) is an artificial environmental endocrine disrupting chemical and commonly used as a monomer of polycarbonate plastics and epoxy resins. The aim of the present study is to investigate the hepatoprotective effects of crocin, a constituent of saffron, against BPA-induced liver toxicity. We showed that treatment of male Wistar rats with 0.5 mg/kg BPA for 30 days increased the level of 8-isoprostane, decreased the level of reduced glutathione, elevated serum levels of aspartate aminotransferase, lactate dehydrogenase, triglyceride, and glucose, and induced periportal inflammation. Western blot results revealed that BPA increased the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK1/2), and mitogen-activated protein kinase-activated protein kinase (MAPKAPK), but not p38. BPA also reduced the Akt signaling activation and upregulated microRNA (miR-122) expression. Moreover, we showed here that crocin 20 mg/kg administration ameliorated liver damage and improved elevated levels of TG and liver enzymes of BPA-treated rats possibly though antioxidant activity, downregulation of miR-122 transcript level and lowering the phosphorylation of JNK, ERK1/2, and MAPKAPK and subsequently their activities. Overall, the findings suggest that crocin possesses hepatoprotective effects against BPA-induced liver toxicity by enhancing the antioxidative defense system and regulation of important signaling pathway activities and miR-122 expression.

Keywords: Antioxidant activity; Bisphenol A; Crocin; Crocus sativus; Hepatotoxicity; MAPK.

MeSH terms

  • Animals
  • Benzhydryl Compounds / toxicity*
  • Carotenoids / administration & dosage*
  • Crocus / chemistry*
  • Down-Regulation / drug effects
  • Endocrine Disruptors / toxicity*
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver Diseases / genetics
  • Liver Diseases / metabolism
  • Liver Diseases / prevention & control*
  • MAP Kinase Signaling System / drug effects
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Oxidative Stress / drug effects*
  • Phenols / toxicity*
  • Plant Extracts / administration & dosage*
  • Protective Agents / administration & dosage
  • Rats
  • Rats, Wistar


  • Benzhydryl Compounds
  • Endocrine Disruptors
  • MicroRNAs
  • Phenols
  • Plant Extracts
  • Protective Agents
  • Carotenoids
  • crocin
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • bisphenol A