Abstract | OBJECTIVE: To evaluate cyclooxygenase-2 (COX-2) inhibition by NS-398 in septic rats with respect to immunologic derangements and hepatic damage. METHODS: Six sham rats ( Sham), 24 rats that underwent experimentally induced sepsis using cecal ligation and puncture (CLP), and 24 rats that underwent induced sepsis after treatment with NS-398 (NS-398), were compared. Sham rats were immediately sacrificed. Six each of CLP and NS-398 animals were sacrificed at 3, 6, 12, and 24 h after induction of sepsis. From each rat was obtained liver for COX-2 mRNA copy number determination and blood for quantification of alanine transaminase (ALT), aspartate aminotransferase (AST), interleukin 10 (IL-10), interleukin 6 (IL-6), and tumor necrosis factor alpha ( TNFalpha) levels, and CD4:CD8 ratios. RESULT:
Sham rats had a lower COX-2 mRNA copy number than NS-398 rats, which had a lower copy number than CLP rats. CLP and NS-938 rats had IL-10 and IL-6 levels above Sham levels. NS-938 rat IL-10 levels were greater and IL-6 levels less than those of CLP rats. For CLP rats, TNF production sharply declined and then increased above Sham levels; NS-398 rat TNF production was consistently mildly elevated above Sham levels. CD4:CD8 ratios sharply dropped over time; NS-398 showed a more modest decline. CLP rats showed unrelenting climbs in AST and ALT values; NS-398 rat levels peaked at 6 h and returned to normal after 12 h; the biochemical evidence of protection against septic liver damage was also seen morphologically, with ultrastructural and histologic normalization of nuclear appearances 12 h after sepsis induction with NS-398 pretreatment. CONCLUSION:
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Authors | Bin Li, Yu Min Li, Xun Li, Bin Shi, Ming Yan He, Xiao Liang Zhu, Wen Ce Zhou, Mitchell S Wachtel, Eldo Frezza |
Journal | The Journal of surgical research
(J Surg Res)
Vol. 157
Issue 1
Pg. 43-7
(Nov 2009)
ISSN: 1095-8673 [Electronic] United States |
PMID | 19765729
(Publication Type: Journal Article)
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Chemical References |
- Cyclooxygenase 2 Inhibitors
- Cytokines
- Nitrobenzenes
- RNA, Messenger
- Sulfonamides
- N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
- Cyclooxygenase 2
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Topics |
- Animals
- Cyclooxygenase 2
(genetics, metabolism)
- Cyclooxygenase 2 Inhibitors
(pharmacology)
- Cytokines
(immunology)
- Hepatocytes
(pathology, ultrastructure)
- Homeostasis
(drug effects, immunology)
- Liver Diseases
(drug therapy, immunology, metabolism)
- Male
- Microscopy, Electron
- Nitrobenzenes
(pharmacology)
- RNA, Messenger
(metabolism)
- Rats
- Rats, Wistar
- Sepsis
(drug therapy, immunology, metabolism)
- Sulfonamides
(pharmacology)
- T-Lymphocytes
(drug effects, immunology)
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