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Antioxidative action of the nitrovasodilator nicorandil: inhibition of oxidative activation of liver microsomal glutathione S-transferase and lipid peroxidation.

Abstract
Antioxidative effects of the nitrovasodilator nicorandil (SG-75) and denitrated SG-75 (SG-86) were examined in vivo and in vitro. When the isolated rat liver was reperfused with Krebs-Henseleit solution after a 90-min ischemia, microsomal GSH S-transferase activity was increased significantly by oxidative modification of the sulfhydryl group of the enzyme. The increase in the transferase activity after ischemia/reperfusion was depressed by SG-75 but not by SG-86. Furthermore, only SG-75 significantly inhibited lipid peroxidation and the activation of microsomal GSH S-transferase induced by hydrogen peroxide treatment of liver microsomes. These data indicate that SG-75 has an antioxidative action and the nitro group of SG-75 may play a critical role for this action.
AuthorsA Naito, Y Aniya, M Sakanashi
JournalJapanese journal of pharmacology (Jpn J Pharmacol) Vol. 65 Issue 3 Pg. 209-13 (Jul 1994) ISSN: 0021-5198 [Print] Japan
PMID7799521 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Antioxidants
  • Propanolamines
  • Vasodilator Agents
  • Niacinamide
  • Nicorandil
  • N-(2-hydroxyethyl)nicotinamide
  • Glutathione Transferase
  • nipradilol
  • Nitroglycerin
  • Isosorbide Dinitrate
Topics
  • Animals
  • Antioxidants (pharmacology)
  • Dose-Response Relationship, Drug
  • Enzyme Activation (drug effects)
  • Glutathione Transferase (metabolism)
  • Isosorbide Dinitrate (pharmacology)
  • Lipid Peroxidation (drug effects)
  • Male
  • Microsomes, Liver (drug effects, enzymology)
  • Niacinamide (analogs & derivatives, pharmacology, therapeutic use)
  • Nicorandil
  • Nitroglycerin (pharmacology)
  • Oxidation-Reduction (drug effects)
  • Propanolamines (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury (chemically induced, drug therapy, enzymology)
  • Structure-Activity Relationship
  • Sympathetic Nervous System (drug effects)
  • Vasodilator Agents (pharmacology, therapeutic use)

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