Effect of ascorbic acid on hepatic vasoregulatory gene expression during polymicrobial sepsis.
The aim of this study was to investigate the effects of ascorbic acid on hepatic vasoregulatory gene expression during polymicrobial sepsis. Rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). Rats received either vehicle (n = 10) or ascorbic acid (AA, 100 mg/kg, n = 10) intravenously immediately after the CLP procedure. Serum aminotransferase levels and hepatic lipid peroxides markedly increased 24 h after CLP and this increase was attenuated by AA treatment. The hepatic concentrations of reduced glutathione decreased in CLP animals. This decrease was inhibited by AA. CLP significantly increased the mRNA level of ET-1 (p < 0.01) and ETB receptor (p < 0.01) in livers; an increase that was prevented by AA treatment. There were no significant changes in ETA mRNA expression among any of the experimental groups. There were significant increases in the mRNA expression of nitric oxide synthases (p < 0.01) and heme oxygenase-1 (p < 0.01) in livers from CLP animals. This increase was prevented by AA treatment. The expression of tumor necrosis factor-alpha and cyclooxygenase-2 mRNAs significantly increased 4.9-fold (p < 0.01) and 4.4-fold (p < 0.01) in livers from CLP animals, respectively. This increase was attenuated by AA treatment. Our data suggest that AA reduces oxidative stress and lipid peroxidation, regulates the hepatic vasoregulatory gene expression in polymicrobial sepsis and thus it could reduce hepatic microvascular dysfunction during sepsis.
Department of Pharmacology, College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu Suwon-si, Gyeonggi-do 440-746, South Korea.
Joo-Young
JY
Kim
Sun-Mee
SM
Lee
D000704:Analysis of Variance; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D017931:DNA Primers; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000378:metabolism*; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017931:DNA Primers; D019332:Endothelin-1; D007527:Isoenzymes; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000637:Transaminases; D005978:Glutathione; D001205:Ascorbic Acid