Karthikeyan K, Bai B R Sarala, Devaraj S Niranjali
Department of Biochemistry, University of Madras, Guindy Campus, Chennai-600 025, India.
Int J Cardiol. 2007 Feb 14;115(3):326-33. doi: 10.1016/j.ijcard.2006.03.016. Epub 2006 Jul 7.
To investigate whether grape seed proanthocyanidins (GSP) might protect the heart against myocardial injury (MI) induced by isoproterenol (ISO), in a rat model.
GSP was administered orally to Wistar albino rats (150-180 g) in three different doses, by gastric gavage (50, 100 and 150 mg kg(-1) GSP), 6 days a week for 5 weeks. At the end of this period, all the rats, except the normal untreated rats that served as the control group, were administered ISO, 85 mg kg(-1) subcutaneously, for 2 consecutive days to induce myocardial injury. After 48 h, rats (n=6 per group) were anaesthetized with anesthetic ether, sacrificed and the levels of biochemical and histological observations of the heart tissues were performed.
Our results suggest that prior administration of GSP maintained the levels of the marker enzymes (AST, ALT, LDH and CK) in all the treatment groups (GSP-50-ISO, GSP-100-ISO and GSP-150-ISO) when compared to ISO-injected rats. The entire baseline groups also showed no significant alterations in serum marker enzyme levels in comparison to that of control group. Interestingly, in this study, there was no significant change in the basal levels of myocardial TBARS, GST, SOD and CAT on administration of GSP in all the three dosages (GSP-50-BL, GSP-100-BL and GSP-150-BL). However, a significant decrease occurred in the levels of GSH and GPx in group GSP-50-BL, which in the absence of any cellular injury (as evidenced by histological studies), is considered to be non-lethal. In the ISO-injected group there was a significant rise in TBARS and a significant decrease in GSH, GPx, GST, SOD and CAT when compared to group control. The administration of GSP maintained the activities of these enzymes close to normal levels when compared to group ISO, which proves the stress stabilizing action of GSP. The biochemical and histological evidence from this study shows that 100 and 150 mg kg(-1) of GSP protected against ISO-induced myocardial injury.
This study demonstrates that GSP has a significant effect in the protection of heart against MI induced by ISO. We believe that pretreatment with GSP may contribute to developing novel strategies in the prevention and treatment of cardiotoxic effects of elevated levels of catecholamine.
在大鼠模型中研究葡萄籽原花青素(GSP)是否可以保护心脏免受异丙肾上腺素(ISO)诱导的心肌损伤(MI)。
将不同剂量的GSP经口灌胃给予Wistar白化大鼠(150 - 180 g),剂量分别为50、100和150 mg·kg⁻¹,每周6天,共5周。在此期间结束时,除作为对照组的未处理正常大鼠外,所有大鼠皮下注射85 mg·kg⁻¹的ISO,连续2天以诱导心肌损伤。48小时后,用麻醉乙醚麻醉大鼠(每组n = 6),处死大鼠并对心脏组织进行生化和组织学观察。
我们的结果表明,与注射ISO的大鼠相比,预先给予GSP可使所有治疗组(GSP - 50 - ISO、GSP - 100 - ISO和GSP - 150 - ISO)中的标志物酶(AST、ALT、LDH和CK)水平保持稳定。与对照组相比,所有基线组的血清标志物酶水平也无显著变化。有趣的是,在本研究中,给予三种剂量的GSP(GSP - 50 - BL、GSP - 100 - BL和GSP - 150 - BL)后,心肌TBARS、GST、SOD和CAT的基础水平均无显著变化。然而,GSP - 50 - BL组中GSH和GPx水平显著降低,在无任何细胞损伤的情况下(组织学研究证明),这被认为是无致死性的。与对照组相比,ISO注射组的TBARS显著升高,GSH、GPx、GST、SOD和CAT显著降低。与ISO组相比,给予GSP可使这些酶的活性维持在接近正常水平,这证明了GSP的应激稳定作用。本研究的生化和组织学证据表明,100和150 mg·kg⁻¹的GSP可预防ISO诱导的心肌损伤。
本研究表明,GSP对保护心脏免受ISO诱导的MI具有显著作用。我们认为,预先用GSP处理可能有助于开发预防和治疗儿茶酚胺水平升高所致心脏毒性作用的新策略。