Antioxidant Potential of a Novel Tetrapeptide Derivative in Isoproterenol-Induced Myocardial Necrosis in Rats

Abstract

A novel tetrapeptide derivative Boc-Lys(Boc)-Arg-Asp-Ser(tbu)-OtBu (PEP1261) has been tested in vivo in isoproterenol (ISO) hydrochloride (HCl)-induced myocardial necrosis in rats. ISO·HCl induces myocardial necrosis in rats which is accompanied by the distinct increase in heart weight, marked electrocardiographic changes, increase in the levels of serum marker enzymes and lipid peroxides and decrease in the levels of antioxidants. PEP1261 (5 mg/kg body weight i.p.) pre- and post-treatment effectively decreases serum marker enzyme levels, while the electrocardiographic changes get restored towards normalcy. PEP1261 also inhibits the action of the free radicals toxicity by increasing the levels of antioxidants and histological studies confirm the above findings. This study shows that PEP1261 could serve as an excellent cardioprotective agent possessing membrane-stabilizing action.

A Novel Tetrapeptide Derivative Exhibits In Vitro Inhibition of Neutrophil-Derived Reactive Oxygen Species and Lysosomal Enzymes Release

“…It was shown recently that the neutrophils characteristically invaded the myocardial tissue during ischemia and they were observed to be the major source of free radicals [2]. The result of this study showing PEP1261 significantly reducing O 2 ∙− , H 2 O 2 , and MPO levels both in the case of stimulated and myocardial rat infarct neutrophils was also in agreement with that of Manikandan et al [36]. …”

Curcumin modulates free radical quenching in myocardial ischaemia in rats

“…Electrocardiography Standard ECG was recorded by Student's Physiograph (INCO, India) under anesthesia as described under (Manikandan et al, 2002) for all the groups. ECG was recorded using standard lead at a chart II speed of 10 cm s −1 with sensitivity set at 1.…”

“…Heart weight to body weight ratio (HW/BW) was calculated by dividing heart weight (g) by body weight (g) and multiplying by 100 (Manikandan et al, 2002).…”

The Role of Akt and Mitogen-Activated Protein Kinase Systems in the Protective Effect of Poly(ADP-Ribose) Polymerase Inhibition in Langendorff Perfused and in Isoproterenol-Damaged Rat Hearts

“…First, we investigated the effect of the novel PARP inhibitor L-2286 on the recovery of energy metabolism in Langendorff perfused hearts during ischemia-reperfusion cycle, and then L-2286 was tested in vivo in isoproterenol-induced myocardial infarction model. As known, subcutaneous administration of the ␤-adrenoceptor agonist isoproterenol produces graded myocardial cell death and rapidly impairs left ventricular function, at least partially, through free radical generation (Grimm et al, 1998;Manikandan et al, 2002). However, to our knowledge no studies have evaluated the intracellular signaling cascades during isoproterenol-induced myocardial infarction.…”

“…It is noteworthy that isoproterenol, a ␤-adrenergic agonist induces extensive cardiomyocyte necrosis by its positive inotropic and chronotropic effect, ranging from patchy subendocardial necrosis to transmural infarction (Teerlink et al, 1994;Grimm et al, 1998). In addition, ISO administration was reported to enhance free radical formation, which might result in both acute and chronic deterioration of hemodynamic variables (Teerlink et al, 1994;Manikandan et al, 2002;Chattopadhyay et al, 2003). Together, the novel PARP inhibitor L-2286 conferred protection in various models with oxidative challenge, including cultured cells, ischemic-reperfused hearts, and in vivo cardiac injury.…”