Razavi Bibi Marjan, Hosseinzadeh Hossein, Abnous Khalil, Khoei Alireza, Imenshahidi Mohsen
Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Pharmaceutical Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Toxicol Ind Health. 2016 Jul;32(7):1237-45. doi: 10.1177/0748233714554941. Epub 2014 Nov 20.
Research has suggested that natural antioxidant, crocin, an active ingredient of saffron, may protect against diazinon (DZN)-induced toxicity. Although increased production of lipid peroxidation by DZN in rat aorta has been shown previously, the effects of DZN on oxidative stress-induced apoptosis in vascular system have not been evaluated. In this study, the effect of crocin on DZN-induced apoptosis in rat vascular system was investigated. The rats were divided into 7 groups: corn oil (control), DZN (15 mg/kg/day, gavage), crocin (12.5, 25, and 50 mg/kg/day, intraperitoneally (i.p.)) + DZN, vitamin E (200 IU/kg, i.p., 3 days a week) + DZN, and crocin (50 mg/kg/day, i.p.). The treatments were continued for 4 weeks. Levels of apoptotic (Bax, caspase 3, and caspase 9) and antiapoptotic proteins (Bcl2) were analyzed by Western blotting. Transcript levels of Bax and Bcl2 genes were determined using quantitative real-time polymerase chain reaction. Results showed DZN-induced apoptosis by activation of caspase 9 and caspase 3 and by increasing the Bax/Bcl2 ratio (both protein and messenger RNA levels). Crocin and vitamin E inhibited apoptosis induced by DZN. In summary, subchronic exposure to DZN induced caspase-mediated apoptosis, and crocin reduced the toxic effects of DZN by inhibiting apoptosis in aortic tissue.
研究表明,天然抗氧化剂藏红花素(一种藏红花的活性成分)可能预防二嗪农(DZN)诱导的毒性。尽管此前已表明DZN会使大鼠主动脉中脂质过氧化产物增加,但DZN对血管系统氧化应激诱导的细胞凋亡的影响尚未得到评估。在本研究中,研究了藏红花素对DZN诱导的大鼠血管系统细胞凋亡的影响。将大鼠分为7组:玉米油(对照组)、DZN(15毫克/千克/天,灌胃)、藏红花素(12.5、25和50毫克/千克/天,腹腔注射(i.p.))+DZN组、维生素E(200国际单位/千克,腹腔注射,每周3天)+DZN组,以及藏红花素(50毫克/千克/天,腹腔注射)组。治疗持续4周。通过蛋白质印迹法分析凋亡蛋白(Bax、半胱天冬酶3和半胱天冬酶9)和抗凋亡蛋白(Bcl2)的水平。使用定量实时聚合酶链反应测定Bax和Bcl2基因的转录水平。结果显示,DZN通过激活半胱天冬酶9和半胱天冬酶3以及增加Bax/Bcl2比值(蛋白质和信使RNA水平)诱导细胞凋亡。藏红花素和维生素E抑制了DZN诱导的细胞凋亡。总之,亚慢性暴露于DZN会诱导半胱天冬酶介导的细胞凋亡,而藏红花素通过抑制主动脉组织中的细胞凋亡降低了DZN的毒性作用。