Evaluation of diazinon-induced hepatotoxicity and protective effects of crocin

Toxicol Ind Health. 2015 Apr;31(4):367-76. doi: 10.1177/0748233713475519. Epub 2013 Feb 13.


Diazinon (DZN) is one of the most widely used insecticides in agricultural pest control. Previous studies have shown that DZN may induce hepatotoxicity. Reactive oxygen species and apoptosis pathways are involved in the toxicity of DZN. Crocin, a constituent of saffron, has hepatoprotective effects due to its antioxidant activity. In this study, we examined the effects of subacute DZN exposure and ameliorating effect of crocin on lipid peroxidation and pathological changes in rat liver. Moreover, protein levels of activated and total caspases-3 and -9 and Bax/Bcl-2 ratio were measured. Five groups of rats were used in the experiment. Corn oil (control), DZN (15 mg/kg per day, orally) and crocin (12.5, 25 and 50 mg/kg per day, intraperitoneally in combination with DZN) were given to male Wistar rats (n = 6) for 4 weeks. The level of malondialdehyde (MDA) increased significantly in DZN group compared with the control group (p < 0.05). MDA level decreased significantly in the group that received DZN plus 25 mg crocin (p < 0.001). No gross or histological evidence of treatment-related damage to the liver after oral exposure to DZN was observed. DZN also induced apoptosis through activation of caspases-9 and -3 and increasing Bax/Bcl-2 ratio. Crocin attenuated the activation of caspases and reduced the Bax/Bcl-2 ratio. It is concluded that subacute exposure to DZN induces oxidative stress-mediated apoptosis and crocin may reduce DZN-induced hepatotoxicity.

Keywords: Bax; Bcl-2; Crocin; Crocus sativus; DZN; caspase-3; caspase-9; hepatotoxicity; malondialdehyde; saffron; subacute toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Carotenoids / pharmacology*
  • Caspases / metabolism
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Cholinesterase Inhibitors / toxicity
  • Diazinon / toxicity*
  • Insecticides / toxicity
  • Lipid Peroxidation / drug effects
  • Liver / chemistry
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Protective Agents / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Wistar
  • bcl-2-Associated X Protein / metabolism


  • Antioxidants
  • Cholinesterase Inhibitors
  • Insecticides
  • Protective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Carotenoids
  • crocin
  • Caspases
  • Diazinon