Balarastaghi Soudabeh, Yazdian-Robati Rezvan, Vahdati Hasani Faezeh, Hosseinzadeh Hossein, Abnous Khalil, Imenshahidi Mohsen, Mohammadzadeh Leila, Birner-Gruenberger Ruth, Razavi Bibi Marjan
Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Iran J Pharm Res. 2021 Spring;20(2):156-172. doi: 10.22037/ijpr.2020.111836.13385.
In this study, the protective effect of crocin on malathion (MTN) induced cardiotoxicity in rats in subacute exposure was evaluated. Rats were divided into 6 groups; control (normal saline); MTN (100 mg/kg); MTN + crocin (10, 20 and 40 mg/kg) and MTN + vitamin E 200 IU/kg. Treatments were continued for two weeks. Creatine phosphokinase MB (CK-MB), malondialdehyde (MDA) and glutathione (GSH) levels were evaluated in heart tissue at the end of treatments. The effect of crocin and MTN on histopathological changes in rat cardiac tissue was also investigated. The alteration of protein profile in the heart of the animals exposed to MTN was evaluated by proteomic approach through two-dimensional gel electrophoresis followed by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) software. MTN induced histopathological damages and elevated the level of cardiac marker CK-MB ( 0.01). The level of MDA increased and the level of GSH reduced ( 0.001). MDA levels were reduced in all crocin plus MTN groups ( 0.001) and vitamin E plus MTN ( < 0.001) groups as compared to MTN groups. However, in the crocin (10 mg/kg) + MTN group, the content of GSH compared to MTN treated rats increased ( 0.001). Protein abundance analysis identified proteins implicated in cardiac necrosis, tricarboxylic acid cycle, cellular energy homeostasis, arrhythmias, heart development, heart failure and cardiovascular homeostasis to be affected by MTN. In summary, MTN may induce damage in the heart tissue of rats following subacute exposure and crocin, as an antioxidant, showed protective effects against MTN cardiotoxicity.
在本研究中，评估了藏红花素对大鼠亚急性暴露于马拉硫磷（MTN）诱导的心脏毒性的保护作用。大鼠分为6组：对照组（生理盐水）；MTN组（100 mg/kg）；MTN + 藏红花素组（10、20和40 mg/kg）以及MTN + 维生素E 200 IU/kg组。治疗持续两周。治疗结束时评估心脏组织中的肌酸磷酸激酶MB（CK-MB）、丙二醛（MDA）和谷胱甘肽（GSH）水平。还研究了藏红花素和MTN对大鼠心脏组织组织病理学变化的影响。通过二维凝胶电泳，随后采用基质辅助激光解吸/电离飞行时间（MALDI-TOF）软件的蛋白质组学方法，评估暴露于MTN的动物心脏中蛋白质谱的变化。MTN诱导了组织病理学损伤并提高了心脏标志物CK-MB的水平（P<0.01）。MDA水平升高而GSH水平降低（P<0.001）。与MTN组相比，所有藏红花素加MTN组（P<0.001）和维生素E加MTN组（P<0.001）的MDA水平均降低。然而，在藏红花素（10 mg/kg）+ MTN组中，与MTN处理的大鼠相比，GSH含量增加（P<0.001）。蛋白质丰度分析确定参与心脏坏死、三羧酸循环、细胞能量稳态、心律失常、心脏发育、心力衰竭和心血管稳态的蛋白质受到MTN的影响。总之，亚急性暴露后MTN可能会诱导大鼠心脏组织损伤，而藏红花素作为一种抗氧化剂，对MTN心脏毒性具有保护作用。
