title: Garlic provides protection to mice heart against isoproterenol-induced oxidative damage: role of nitric oxide.
abstract: 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 mgkg(-1)day(-1) orally) for 30 days. In another set of experiment, mice were pre-treated with saline, aqueous garlic homogenate (AGH) (250 mgkg(-1)day(-1) for 30 days), and AGH (30 days) along with L-NAME (20 mgkg(-1)day(-1) i.p. for last 7 days) before inducing acute myocardial infarction by isoproterenol (s.c. injection of isoproterenol 150 mgkg(-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 mgkg(-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 β 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.
authors.affiliation: Division of Pharmacology and Chemical Biology, Indian Institute of Chemical Technology (IICT), Hyderabad 500607, India.
authors.forename: Tarak Nath
authors.initials: TN
authors.lastname: Khatua
authors.forename: Raju
authors.initials: R
authors.lastname: Padiya
authors.forename: Santosh
authors.initials: S
authors.lastname: Karnewar
authors.forename: Madhusudana
authors.initials: M
authors.lastname: Kuncha
authors.forename: Sachin B
authors.initials: SB
authors.lastname: Agawane
authors.forename: Srigiridhar
authors.initials: S
authors.lastname: Kotamraju
authors.forename: Sanjay Kumar
authors.initials: SK
authors.lastname: Banerjee
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002460:Cell Line; D002950:Citrate (si)-Synthase / Q000378:metabolism; D042783:Endothelial Cells; D005737:Garlic / Q000737:chemistry*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007545:Isoproterenol / Q000009:adverse effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002316:Cardiotonic Agents; D010936:Plant Extracts; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D015094:3-Hydroxyacyl CoA Dehydrogenases; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D002950:Citrate (si)-Synthase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester