Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1911947 | Free Radical Biology and Medicine | 2006 | 12 Pages |
Abstract
Nitric oxide is known to modulate intracellular glutathione levels, but the relationship between nitric oxide synthesis and glutathione metabolism during endotoxemia is unknown. The present study was designed to examine the effects of increased nitric oxide formation on hepatic glutathione synthesis and antioxidant defense in endotoxemic mice. Our results demonstrate that hepatic glutathione synthesis is decreased for 24 h following injection of lipopolysaccharide (LPS). Administration of the cysteine precursor, L-2-oxothiazolidine-4-carboxylic acid (OTZ), failed to normalize hepatic glutathione concentration, and suggests that decreased γ-glutamylcysteine ligase activity is primarily responsible for the decrease in hepatic glutathione levels during endotoxemia. Inhibition of nitric oxide synthesis prevented the endotoxin-induced changes in hepatic and plasma glutathione status and up-regulated liver glutathione and cysteine synthesis pathways at the level of gene expression. Furthermore, whereas the activity of glutathione peroxidase and glutathione S-transferase decreased during endotoxemia, both of these changes were prevented by inhibition of nitric oxide synthesis. In conclusion, increased nitric oxide synthesis during endotoxemia causes marked changes in glutathione flux and defenses against oxidative stress in the liver.
Keywords
LPScystathionaseAMGl-2-Oxothiazolidine-4-carboxylic acidGSHGAPDHRT-PCRNOSl-NAMENω-nitro-l-arginine methyl esterAminoguanidineAntioxidant enzymesCysteinelipopolysaccharideγ-glutamylcysteine ligaseNitric oxidenitric oxide synthasereverse transcription polymerase chain reactionGlutathioneglyceraldehyde 3-phosphate dehydrogenase
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Authors
Seyedmehdi Payabvash, Mohammad Hossein Ghahremani, Ardeshir Goliaei, Ali Mandegary, Hamed Shafaroodi, Massoud Amanlou, Ahmad Reza Dehpour,