Protective effect of glutathione against lipopolysaccharide-induced inflammation and mortality in rats.
OBJECTIVE
To investigate protective effect of glutathione (GSH) against lipopolysaccharide (LPS)-induced inflammation and mortality in rats.


METHODS
Male Sprague-Dawley rats were injected intraperitoneally (i. p.) with GSH (40 mg/kg) 30 min prior to LPS injection (20 mg/kg). Animal survival rate and the production of nitric oxide in serum were measured. Morphology of lung was observed using hematoxylin and eosin staining. Western blotting was used to assess the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and the phosphorylation of p38 in rat peritoneal macrophages.


RESULTS
GSH significantly decreased LPS-induced mortality, inhibited serum NO production and eliminated lung histological injury. Furthermore, GSH inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and the phosphorylation of p38 in LPS-stimulated rat peritoneal macrophages.


CONCLUSIONS
These results indicated that GSH suppressed LPS-induced systemic inflammatory response in rats and p38 MAPK signal pathway was involved in this process.
Sun
S
S
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.
Zhang
H
H
Xue
B
B
Wu
Y
Y
Wang
J
J
Yin
Z
Z
Luo
L
L
D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005978:Glutathione / Q000008:administration & dosage / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D015996:Survival Rate; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione