Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced myocardial necrosis: a new therapeutic implication.
Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced myocardial necrosis: a new therapeutic implication.
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DOI：
10.1186/1479-5876-11-80
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发表时间：
2013-03-26
影响因子：
7.4
通讯作者：
Banerjee SK
中科院分区：
文献类型：
--
作者：
Gupta P;Kanwal A;Putcha UK;Bulani Y;Sojitra B;Khatua TN;Kuncha M;Banerjee SK
利托那韦是一种 HIV 蛋白酶抑制剂。除了抗病毒作用外，利托那韦还直接抑制胰岛素调节的葡萄糖转运蛋白 GLUT4，并阻止葡萄糖进入脂肪和肌肉细胞。然而，利托那韦对心肌坏死期间心脏 GLUT4 抑制的影响尚未研究。在本研究中，我们评估了利托那韦在体内异丙肾上腺素诱导的心肌坏死中的作用，并与非选择性 SGLT 抑制剂根皮苷的效果进行了比较。向小鼠施用异丙肾上腺素 (ISO)（150 mg/kg/天，腹腔注射连续 2 天）以引起心肌坏死。在给予异丙肾上腺素之前，对两组不同的小鼠给予根皮苷（400 mg/kg/天，腹腔注射，每天两次，持续 2 天）和利托那韦（10 mg/kg/天，腹腔注射，每天两次，持续 2 天）。异丙肾上腺素 (ISO)（150 mg/kg/天，腹腔注射，连续 2 天）导致心脏/体重比显着增加（p<<0.05），并且血清标志物即 SGOT 和 CK 显着增加（p<<0.05），导致心肌坏死；和心脏组织病理学变化。 ISO 给药后，观察到心肌 SOD 和过氧化氢酶活性以及 GSH 水平显着降低（p<0.05），同时心肌 TBARS 和一氧化氮水平显着升高（p<0.05）。然而，根皮苷（一种 SGLT1 抑制剂）被发现对 ISO 诱导的心肌坏死具有部分保护作用，如心脏/体重比和心肌一氧化氮水平显着降低所观察到的。心肌 SOD 和过氧化氢酶活性显着增加，但没有组织病理学改变。另一方面，通过心脏/体重比、血清标志物、抗氧化酶活性和组织病理学改变的正常化观察到，服用利托那韦（一种非特异性GLUT抑制剂）表现出完全的保护作用。心脏匀浆的体外研究证实，在异丙肾上腺素不存在和存在的情况下，利托那韦和根皮苷没有抗氧化作用。我们的研究得出结论，利托那韦（一种非特异性 GLUT 抑制剂）对儿茶酚胺诱导的心肌坏死具有完全保护作用。
Ritonavir is a HIV protease inhibitor. In addition to its antiviral effect, Ritonavir directly inhibits the insulin-regulated glucose transporter GLUT4 and blocks glucose entry into fat and muscle cells. However, the effect of Ritonavir on cardiac GLUT4 inhibition during myocardial necrosis is not investigated. In the present study, we evaluated the role of Ritonavir in isoproterenol-induced myocardial necrosis in vivo and compared the effect with Phlorizin, a nonslective SGLTs inhibitor. Isoproterenol (ISO) (150 mg/kg/day, i.p for 2 consecutive days) was administered to mice to cause myocardial necrosis. Phlorizin (400 mg/kg/day i.p twice daily for 2 days) and Ritonavir (10 mg/kg/day i.p twice daily for 2 days) were administered in two different groups of mice before isoproterenol administration. Isoproterenol (ISO) (150 mg/kg/day, i.p for 2 consecutive days) administration caused significant (p < 0.05) increase in heart/body weight ratio, and myocardial necrosis as evident by significant (p < 0.05) increase in serum markers i.e. SGOT and CK; and cardiac histopathological changes. Significant (p < 0.05) reduction in myocardial SOD and catalase activities, and GSH level along with a significant (p < 0.05) rise in myocardial TBARS and nitric oxide levels were observed after ISO administration. However, administration of phlorizin, a SGLT1 inhibitor has been found to exhibit partial protection in ISO induced myocardial necrosis, as observed by significant decrease in heart/body weight ratio and myocardial nitric oxide level; significant increase in myocardial SOD and catalase activities along with no histopathological alterations. On the other hand, administration of ritonavir, a nonspecific GLUT inhibitor has been found to exhibit complete protection as observed by normalisation of heart/body weight ratio, serum markers, antioxidant enzymes activities and histopathological alterations. In vitro study with heart homogenate confirmed no antioxidant effect of ritonavir and phlorizin in the absence and presence of isoproterenol. Our study concluded that ritonavir, a nonspecific GLUT inhibitors showed complete protection in catecholamine induced myocardial necrosis.
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影响因子：
4
作者：
Zhou, LB;Cryan, EV;Demarest, KT
通讯作者：
Demarest, KT
DOI：
10.1152/ajpcell.1997.273.4.c1371
发表时间：
1997-10-01
影响因子：
5.5
作者：
Kanai, AJ;Mesaros, S;Malinski, T
通讯作者：
Malinski, T
影响因子：
9.3
作者：
Farvin, KHS;Anandan, R;Thankappan, TK
通讯作者：
Thankappan, TK
影响因子：
3.9
作者：
Khatua, Tarak Nath;Padiya, Raju;Banerjee, Sanjay Kumar
通讯作者：
Banerjee, Sanjay Kumar
影响因子：
4.8
作者：
Montessuit, C;Thorburn, A
通讯作者：
Thorburn, A