Protective Effect of Kolaviron on Cyclophosphamide-Induced Cardiac Toxicity in Rats

Abstract

Background. Cyclophosphamide (CP) is a nitrogen mustard alkylating drug used for the treatment of chronic and acute malignant lymphomas, myeloma, leukemia, neuroblastoma, adenocarcinoma, retinoblastoma, breast carcinoma, and immunosuppressive therapy. Despite its vast therapeutic uses, it is known to cause severe cardiac toxicity. Kolaviron (KV), a Garcinia kola seed extract containing a mixture of flavonoids, is reputed for its antioxidant and membrane stabilizing properties. Objective. This study investigated the protective effect of KV on CP-induced cardiotoxicity in rats. Methods. Thirty rats were used, and they were divided into 6 groups of 5 rats each. Group I received 2 mL/kg propylene glycol orally for 14 days; group II received CP (50 mg/kg/d, intraperitoneally [i.p.]) for 3 days; groups III and IV received 200 and 400 mg/kg/d KV, respectively, orally for 14 days and groups V and VI were pretreated with 200 and 400 mg/kg/d KV, respectively, orally for 14 days followed by CP (50 mg/kg/d, i.p.) for 3 days. Results. CP treatment resulted in a significantly lower food consumption and body weight in rats. The lactate dehydrogenase and creatine kinase enzymes in cardiac tissues of rats treated with CP were significantly higher. In cardiac tissues, 3-day doses of CP resulted in significantly higher heart weight, cardiac troponin I, myeloperoxidase, malondialdehyde, hydrogen peroxide and lower superoxide dismutase, catalase, glutathione peroxidase activities, and reduced glutathione levels. Histological examination of cardiac tissues showed sign of necrosis of myocardium after CP treatment. However, administration of KV at 200 and 400 mg/kg for 14 days prior to CP treatment, increase food consumption, body weight, and attenuates the biochemical and histological changes induced by CP. Conclusions. These results revealed that KV attenuates CP-induced cardiotoxicity by inhibiting oxidative stress and preserving the activity of antioxidant enzymes.