Effect of a novel tetrapeptide derivative in a rat model of isoproterenol induced myocardial necrosis |
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Authors: | Ramesh Chintala Venkataramana Malarvannan Pannirselvam Jayakumar Rajadas Jayasundar Shanmugasundaram Puvanakrishnan Rengarajulu |
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Institution: | (1) Department of Biotechnology, Central Leather Research Institute, Adyar, Madras, 600 020, India;(2) Department of Pharmacology and Toxicology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Madras, 600 007, India;(3) Bioorganic Laboratory, Central Leather Research Institute, Adyar, Madras, 600 020, India |
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Abstract: | Isoproterenol hydrochloride (ISO), a beta adrenergic agonist, is known to cause ischemic necrosis in rats. Cardiotoxicity of three different doses of ISO were studied using physiological, biochemical and histopathological parameters. The effects of single and double dose of ISO were analysed, which illustrated that single ISO dose was more cardiotoxic than double ISO dose due to ischemic preconditioning. The tetrapeptide derivatives L-lysine-L-arginine-L-aspartic acid-L-serine (tetrapeptide A) and di-tert.butyloxycarbonyl-L-lysine-L-arginine-L-aspartic acid-tert.butyl O-tert.butyl-L-serinate (tetrapeptide B) along with acetylsalicylic acid as positive control were analysed at different time points for their cardioprotective effect. The results demonstrated that optimal protective effects were observed by pretreatment with 5 mg/kg of tetrapeptide B and this was found to be slightly better than that of acetylsalicylic acid. A lesser degree of cardioprotection was noticed when low doses of tetrapeptide B were administered. This study clearly showed that single dose of ISO (50 mg/kg, s.c.) induced myocardial necrosis could be used as a model to assess cardiovascular drugs and in this model, it was demonstrated that the tetrapeptide B could exhibit optimal cardioprotective effect. |
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Keywords: | myocardial necrosis isoproterenol HCl tetrapeptide cardioprotective effect |
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