Erdosteine salvages cardiac necrosis: Novel effect through modulation of MAPK and Nrf‐2/HO‐1 pathway,Journal of Biochemical and Molecular Toxicology

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Erdosteine salvages cardiac necrosis: Novel effect through modulation of MAPK and Nrf‐2/HO‐1 pathway
Journal of Biochemical and Molecular Toxicology ( IF 3.2 ) Pub Date : 2020-07-30 , DOI: 10.1002/jbt.22590
Ekta Mutneja ₁ , Vipin K Verma ₁ , Salma Malik ₁ , Anil K Sahu ₁ , Ruma Ray ₂ , Jagriti Bhatia ₁ , Dharamvir S Arya ₁

Affiliation

Isoproterenol (ISO) induced oxidative stress and inflammation is involved in the pathogenesis of myocardial necrosis. To optimize the effect of erdosteine against myocardial necrosis, male albino Wistar rats were divided into eight groups (n = 6), that is, normal, ISO‐control, erdosteine pretreatment with ISO. Rats were administered erdosteine orally for 28 days. Two doses of ISO (85 mg/kg), s.c. were given to ISO‐C and erdosteine treatment groups on the 27th and 28th day. On the 29th day, hemodynamic parameters were recorded and the heart was excised for further parameters. In ISO‐C rats, significantly increased levels of inflammatory markers, pro‐oxidants, and structural damage were observed as compared with normal group. Furthermore, immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling revealed an increased expression of apoptotic proteins. Erdosteine at 80 mg/kg reversed the deleterious effects of ISO and normalized myocardium. Erdosteine showed anti‐inflammatory, antiapoptotic, and antioxidant activities through inhibition of MAPK and Nrf‐2/HO‐1 pathways. To conclude, erdosteine was found protective in ISO‐induced myocardial necrosis through MAPK and Nrf‐2/HO‐1 pathway.

中文翻译：

Erdosteine挽救心脏坏死：通过调节MAPK和Nrf-2-HO-1途径的新作用

异丙肾上腺素（ISO）诱导的氧化应激和炎症参与心肌坏死的发病机制。为了优化厄多斯坦对心肌坏死的作用，将雄性白化Wistar大鼠分为八组（n = 6），即使用ISO进行正常的，ISO对照的Erdosteine预处理。给大鼠口服Erdosteine 28天。第27天和第28天，分别向ISO-C和erdosteine治疗组给予了两剂ISO（85 mg / kg）sc。在第29天，记录血流动力学参数，并切下心脏以获得其他参数。与正常组相比，在ISO‐C大鼠中，观察到炎症标志物，促氧化剂和结构损伤的水平显着增加。此外，免疫组化和末端脱氧核苷酸转移酶dUTP缺口末端标记显示凋亡蛋白的表达增加。80 mg / kg的Erdosteine逆转了ISO和标准化心肌的有害作用。Erdosteine具有抗炎，抗凋亡，通过抑制MAPK和Nrf-2-HO-1途径来发挥抗氧化活性。总而言之，通过MAPK和Nrf / 2 / HO-1途径，发现厄多司坦对ISO诱发的心肌坏死具有保护作用。

更新日期：2020-07-30

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