ผลของ morelloflavone จากผลมะพูดต่อการหดตัวของหลอดเลือดแดงธอราสิคในหนูที่ได้รับซิสพลาติน

Abstract

One of the adverse effects in using a chemotherapeutic drug, cisplatin, is cardiovascular complication. Cisplatin effect on the blood vessels includes an increase in reactive oxygen species which may impair vascular smooth muscle relaxation. A plant biflavonoid extracted from Garcinia dulcis (Kurz), morelloflavone, has been shown to possess robust antioxidant activity and recently caused vasodilation via endothelium dependent nitric oxide signaling pathway in both normotensive and hypertensive rats. This study aimed to investigate an acute and protective effect of morelloflavone on the contractile function, oxidative status and structural damage of cisplatin-treated rat thoracic aorta. Male Wistar rats were used and either cisplatin (7.5 mg/kg) or vehicle (0.9% NaCi) was given intraperitoneally. An acute vasorelaxant effect of morelloflavone (10*12 - 10% M) was tested in isolated thoracic aortic rings of control (endothelium-intact and denuded) and cisplatin-treated rat on day 7 after the injection. To study the protective role of morelloflavone on the contractile function of the aortic rings, rats were divided into three groups including vehicle control, cisplatin and cisplatin + morelloflavone treated group. Morelloflavone (0.1, 1, 10 mg/kg, i.p.) were given twice, 1 day and 10 min before cisplatin injection. Seven days after the treatment, the contractile responses to 10*'° - 10 M phenylephrine (PE), 10*12 - 10-5 M acetylcholine (ACh) or sodium nitroprusside (SNP) were investigated. It is found that the vasorelaxation of morelloflavone is endothelium dependent and the contraction response to PE was significantly higher in cisplatin treated group whereas the relaxation responses to ACh found significantly lower when compared to control. Morelloflavone (1 mg/kg) treatment was able to improve the contractile responses to PE, ACh and SNP. Plasma malondialdehyde level which increased significantly in cisplatin group was also subsided by morelloflavone treatment suggesting its antioxidant action occurred along with the vasorelaxation effect. Histological examination revealed the tunica media proliferation in cisplatin group was restored by morelloflavone treatment.