Garlic provides protection to mice heart against isoproterenol-induced oxidative damage: Role of nitric oxide
Garlic provides protection to mice heart against isoproterenol-induced oxidative damage: Role of nitric oxide
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DOI：
10.1016/j.niox.2012.03.004
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发表时间：
2012-06-30
影响因子：
3.9
通讯作者：
Banerjee, Sanjay Kumar
中科院分区：
文献类型：
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作者：
Khatua, Tarak Nath;Padiya, Raju;Banerjee, Sanjay Kumar
大蒜被广泛认为是一种心脏保护剂。然而，其心脏保护作用的分子机制尚未完全确定。在这里，我们假设水大蒜匀浆可能介导的心脏保护作用，通过一氧化氮（NO）。用盐水和大蒜匀浆水溶液（口服250和500 mg/kg/d）喂养小鼠30天。在另一组实验中，在通过异丙肾上腺素（s.c.）诱导急性心肌梗死之前，用盐水、水性大蒜匀浆（AGH）（250 mg/kg/天，持续30天）和AGH（30天）沿着L-NAME（20 mg/kg/天，腹腔注射，持续7天）预处理小鼠。注射异丙肾上腺素150 mg kg（-1）d（-1），持续2天），并在48 h后处死。大蒜250和500 mg kg（-1）剂量喂养后，观察到血清NO水平呈剂量依赖性增加。饲喂大蒜后，血清SGPT和SGOT水平无明显变化，但血清LDH水平显著降低。大蒜诱导的NO形成在人主动脉内皮细胞（HAEC）中得到进一步证实。给予异丙肾上腺素导致内源性抗氧化剂显著减少，心肌过氧化氢酶GSH和GPx活性以及线粒体酶活性如柠檬酸合酶和13羟酰辅酶A脱氢酶。大蒜匀浆能明显减轻异丙肾上腺素引起的上述心脏损害。然而，当大蒜与一氧化氮合酶（NOS）的非特异性抑制剂L-NAME一起给药时，大蒜的这种有益作用被削弱。此外，与异丙肾上腺素治疗组相比，在L-NAME治疗组中观察到心肌TBARS显著增加和总抗氧化活性降低。对照组小鼠给予L-NAME后，血清和心脏NO水平降低，但氧化应激指标无明显变化。总之，我们的研究提供了新的证据，大蒜匀浆是通过NO信号通路在小鼠心肌梗死保护。(C)2012 Elsevier Inc. All rights reserved.
Garlic has been widely recognized as a cardioprotective agent. However, the molecular mechanism of its cardioprotective effects is not well established. Here we hypothesized that aqueous garlic homogenate may mediate cardioprotection via nitric oxide (NO). Mice were fed with saline and aqueous garlic homogenate (250 and 500 mg kg(-1) day(-1) orally) for 30 days. In another set of experiment, mice were pre-treated with saline, aqueous garlic homogenate (AGH) (250 mg kg(-1) day(-1) for 30 days), and AGH (30 days) along with L-NAME (20 mg kg(-1) day(-1) i.p. for last 7 days) before inducing acute myocardial infarction by isoproterenol (s.c. injection of isoproterenol 150 mg kg(-1)day(-1) for 2 days) and sacrificed after 48 h. Dose dependent increase in serum NO level was observed after garlic 250 and 500 mg kg(-1) dose feeding. While no change in serum SGPT and SGOT level, a significant decrease in serum LDH level was observed after garlic feeding. Garlic-induced NO formation was further confirmed in human aortic endothelial cells (HAEC). Administration of isoproterenol caused a significant decrease in endogenous antioxidants i.e., myocardial catalase. GSH and GPx activity, and mitochondrial enzyme activities like citrate synthase and 13 hydroxyacyl CoA dehydrogenase. All those deleterious cardiac changes induced by isoproterenol were significantly attenuated by garlic homogenate. However this beneficial effect of garlic was blunted when garlic was administered with L-NAME, a nonspecific inhibitor of nitric oxide synthase (NOS). Further, a significant increase in myocardial TBARS and decrease in total antioxidant activity was observed in L-NAME treated group compared to isoproterenol treated group. Administration of L-NAME in mice from control group lowered serum and cardiac NO levels without any change of oxidative stress parameters. In conclusion, our study provides novel evidence that garlic homogenate is protective in myocardial infarction via NO-signaling pathway in mice. (C) 2012 Elsevier Inc. All rights reserved.