EFFECT OF SOME PHENOLICS ON ISOPROTERENOL-INDUCED CARDIOTOXICITY IN WISTAR ALBINO RATS

Abstract

This study was designed to examine the cardioprotective effect of selected phenolic compounds on isoproterenol-induced cardiotoxicity in albino rats. Fifty four male albino rats (Wistar strain), weighing 250 ± 40 g and divided into nine groups (n = 6), were used for the experiment. Group I was administered distilled water throughout the period of experiment while group II-IX received distilled water, quercetin (20 mg/kg), catechin (50 mg/kg), courmaric acid (100 mg/kg), combined doses of quercetin (20 mg/kg) and courmaric acid (100 mg/kg), combined doses of quercetin (20 mg/kg) and catechin (50 mg/kg), combined doses of courmaric acid (100 mg/kg) and catechin (50 mg/kg), and ramipril (2.5 mg/kg) respectively, for 12 consecutive days and in addition received isoproterenol (ISP) (100 mg/kg b.w) on the 11th and 12th day. Animals were sacrificed 24 h after the last administration and blood and heart samples were analyzed for markers of cardiac injury. Heart tissues were examined for histoarchitectural alterations. Results showed that there were increases in serum triglyceride (TRIG) (1.31 ± 0.11 mmol/l) and cholesterol (CHOL) (8.47 ± 0.29 mmol/l) levels in the ISP-challenged group compared with the control (0.51 ± 0.05 mmol/l and 1.53 ± 0.01 mmol/l respectively) (P < 0.05). There were also significant increases in serum activities of alkaline phosphatase (ALP) (41.83 ± 4.76 U/l), aspartate aminotransferase (AST) (16.43 ± 1.00 U/l), alanine aminotransferase (ALT) (5.31 ± 0.44 U/l), lactate dehydrogenase (LDH) (137.37 ± 11.80 U/l) and creatine kinase (CK) (737.91 ± 64.00 U/l) compared with the control group (15.34 ± 1.15, 9.82 ± 0.64, 3.96 ± 0.95, 73.98 ± 8.45 and 404.44 ± 38.00 U/l respectively). However, a significant decrease was recorded for serum glutathione (GSH) level in the ISP-intoxicated group (99.00 ± 2.40 μg/ml) compared to the control value (966.67 ± 73.36 μg/ml). The fasting blood sugar (FBS) concentration was also increased in the ISP-challenged group (140.80 ± 7.57 mg/dl) compared to the control group (78.50 ± 6.15 mg/dl) (P < 0.05). Histopathological evaluation of ISP-intoxicated group revealed the presence of large foci of severe myofibre necrosis and loss of nuclear materials of cells in the heart which were absent in the control. Pretreatment with individual or combined phenolics ameliorated the alterations in biochemical parameters and the damage to cardiac myofibrils resulting from ISP intoxication. In general, treatment with the single phenolics appeared to be more effective in correcting ISP-induced aberrations in the activity of the studied enzymes and the level of GSH while the combined treatment appeared more potent in ameliorating imbalances in the lipid and FBS levels. Among the single phenolics, the level of effectiveness is roughly in the order: coumaric acid < catechin < quercetin while for the combined phenolics, it is roughly in the order: courmaric acid-catechin < quercetin-coumaric acid < quercetin-catechin. The phenolics, for the most part proved more effective than the standard drug, ramipril. The present study showed that phenolics and other phytochemicals may