Antioxidative action of the nitrovasodilator nicorandil: inhibition of oxidative activation of liver microsomal glutathione S-transferase and lipid peroxidation.
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.
Naito
A
A
Laboratory of Physiology and Pharmacology, School of Health Sciences, University of the Ryukyus, Okinawa, Japan.
Aniya
Y
Y
Sakanashi
M
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005982:Glutathione Transferase / Q000378:metabolism*; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D020108:Nicorandil; D005996:Nitroglycerin / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology; D013329:Structure-Activity Relationship; D013564:Sympathetic Nervous System / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D011412:Propanolamines; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; C030731:N-(2-hydroxyethyl)nicotinamide; D005982:Glutathione Transferase; C036089:nipradilol; D005996:Nitroglycerin; D007548:Isosorbide Dinitrate