title: Nitric oxide modulates glutathione synthesis during endotoxemia.
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 gamma-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.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran.
authors.forename: Seyedmehdi
authors.initials: S
authors.lastname: Payabvash
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Ghahremani
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Goliaei
authors.forename: Ali
authors.initials: A
authors.lastname: Mandegary
authors.forename: Hamed
authors.initials: H
authors.lastname: Shafaroodi
authors.forename: Massoud
authors.initials: M
authors.lastname: Amanlou
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D001835:Body Weight; D002374:Catalase / Q000378:metabolism; D003545:Cysteine / Q000502:physiology; D004195:Disease Models, Animal; D004435:Eating; D019446:Endotoxemia / Q000378:metabolism*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood; D007267:Injections; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008297:Male; D051379:Mice; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000097:blood; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D002374:Catalase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D003545:Cysteine