Lari Parisa, Abnous Khalil, Imenshahidi Mohsen, Rashedinia Marzieh, Razavi Marjan, Hosseinzadeh Hossein
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran.
Department of Medicinal Chemistry, Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran.
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.
二嗪农（DZN）是农业害虫防治中使用最广泛的杀虫剂之一。先前的研究表明，DZN可能会诱发肝毒性。活性氧物种和凋亡途径参与了DZN的毒性作用。藏红花的成分西红花苷因其抗氧化活性而具有肝脏保护作用。在本研究中，我们检测了亚急性暴露于DZN的影响以及西红花苷对大鼠肝脏脂质过氧化和病理变化的改善作用。此外，还检测了活化型和总半胱天冬酶-3和-9的蛋白水平以及Bax/Bcl-2比值。实验使用了五组大鼠。将玉米油（对照组）、DZN（每天15毫克/千克，口服）和西红花苷（每天12.5、25和50毫克/千克，与DZN联合腹腔注射）给予雄性Wistar大鼠（n = 6），持续4周。与对照组相比，DZN组丙二醛（MDA）水平显著升高（p < 0.05）。接受DZN加25毫克西红花苷的组中MDA水平显著降低（p < 0.001）。口服DZN后，未观察到与治疗相关的肝脏损伤的大体或组织学证据。DZN还通过激活半胱天冬酶-9和-3以及增加Bax/Bcl-2比值诱导凋亡。西红花苷减弱了半胱天冬酶的激活并降低了Bax/Bcl-2比值。结论是，亚急性暴露于DZN会诱导氧化应激介导的凋亡，而西红花苷可能会降低DZN诱导的肝毒性。
