Shrestha Ayush, Krishnamurthy Praveen T, Thomas Pooja, Hammock Bruce D, Hwang Sung H
Department of Pharmacology, JSS College of Pharmacy (A constituent college of JSS University, Mysore), Ootacamund, Tamilnadu, India.
J Pharm Pharmacol. 2014 Sep;66(9):1251-8. doi: 10.1111/jphp.12251. Epub 2014 Apr 2.
To determine the protective role of a soluble epoxide hydrolase(sEH) inhibitor, trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido] cyclohexyloxy} benzoic acid (t-TUCB), in isoproterenol (ISO)-induced myocardial ischaemic injury in vivo.
Cardioprotective activity of t-TUCB was studied against ISO-induced myocardial ischaemic injury in male Wistar rats. Cardioprotection was assessed by measuring elecrocardiographic (EKG), serum lactate dehydrogenase (LDH) and creatine kinase (CK-MB) levels, cardiac calcium and antioxidant levels, and also by measuring infarct size in the cardiac tissue.
Pretreatment with t-TUCB at 3, 10 and 30 mg/kg orally for a period of 14 days significantly prevented the changes in EKG parameters (QTc interval prolongation, ST height depression, pathological Q waves formation and T-wave inversion), serum cardiac biomarkers (CK-MB and LDH), relative heart weight, myocardial calcium levels, infarct size and the oxidative status in the cardiac tissue (lipid peroxidation, catalase and superoxide dismutase levels) when compared with the untreated control animals (P < 0.05).
The sEH inhibitor t-TUCB significantly prevents ISO-induced myocardial ischaemic injury in rats. This study provides a preliminary confirmation of the efficacy of t-TUCB by oral administration in rats.
确定可溶性环氧化物水解酶（sEH）抑制剂反式-4-{4-[3-(4-三氟甲氧基苯基)-脲基]环己氧基}苯甲酸（t-TUCB）在异丙肾上腺素（ISO）诱导的体内心肌缺血性损伤中的保护作用。
研究t-TUCB对雄性Wistar大鼠ISO诱导的心肌缺血性损伤的心脏保护活性。通过测量心电图（EKG）、血清乳酸脱氢酶（LDH）和肌酸激酶（CK-MB）水平、心脏钙和抗氧化剂水平，以及测量心脏组织中的梗死面积来评估心脏保护作用。
与未治疗的对照动物相比，以3、10和30mg/kg的剂量口服t-TUCB预处理14天，可显著预防EKG参数（QTc间期延长、ST段抬高压低、病理性Q波形成和T波倒置）、血清心脏生物标志物（CK-MB和LDH）、相对心脏重量、心肌钙水平、梗死面积和心脏组织氧化状态（脂质过氧化、过氧化氢酶和超氧化物歧化酶水平）的变化（P<0.05）。
sEH抑制剂t-TUCB可显著预防ISO诱导的大鼠心肌缺血性损伤。本研究初步证实了t-TUCB经口服给药对大鼠的有效性。
