The effect of nitroglycerin tolerance on oxidative stress and anaerobic sulfur metabolism in rat tissues.
The present results indicated that tolerance to nitroglycerin (glycerin trinitrate, GTN) increased the hepatic and renal level of reactive oxygen species, malondialdehyde, and glutathione peroxidase (PO(x)) and decreased superoxide dismutase activity, whereas non-protein thiols remained unchanged in both organs. In the liver (but not in the kidney) glutathione S-transferase (GST), catalase and rhodanese activities decreased and the sulfane sulfur level also dropped. Unlike in the liver, gamma-glutamyl transpeptidase (gammaGT) activity in the kidney declined. On the other hand, hepatic S-nitrosothiols (SNT) rose while renal SNT declined. As no concomitant changes in the nitric oxide (NO) level were observed in either organ, the results suggested that under nitroglycerin tolerance NO was stored in the liver in the form of SNT. In conclusion, the results obtained in the liver and kidney confirm the involvement of oxidative stress in the pathomechanism of GTN tolerance, and reveal the diverse effects of this phenomenon on the gammaGT and GST activity and SNT level in both organs. We observed for the first time that GTN tolerance could be accompanied by the disruption of hepatic anaerobic cysteine metabolism, associated with sulfane sulfur and rhodanese activity.
Dudek
Magdalena
M
Laboratory of Pharmacological Screening, Jagiellonian University, Collegium Medicum, 9, Medyczna Street, PL 30-688 Kraków, Poland.
Bilska
Anna
A
Bednarski
Marek
M
Iciek
Małgorzata
M
Kwiecień
Inga
I
Sokołowska-Jezewicz
Maria
M
Filipek
Barbara
B
Włodek
Lidia
L
D000693:Anaerobiosis; D000818:Animals; D004361:Drug Tolerance; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013455:Sulfur / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D009569:Nitric Oxide; D008315:Malondialdehyde; D013455:Sulfur; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005996:Nitroglycerin