Open AccessSoluble epoxide hydrolase inhibitor, t ‐TUCB , protects against myocardial ischaemic injury in rats
Author(s) -
Shrestha Ayush,
Krishnamurthy Praveen T.,
Thomas Pooja,
Hammock Bruce D.,
Hwang Sung H.
Publication year - 2014
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.12251
Subject(s) - lactate dehydrogenase , lipid peroxidation , creatine kinase , medicine , pharmacology , cardioprotection , oxidative stress , qt interval , chemistry , superoxide dismutase , endocrinology , ischemia , biochemistry , enzyme
Objectives 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 . Methods 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. Key findings 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). Conclusion 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.