Bicuculline methiodide attenuates hepatic injury and decreases mortality in septic rats: role of cytokines.
Bicuculline methiodide attenuates inflammation by inhibiting the production of proinflammatory cytokines, such as tumor necrosis factor-alpha, and by increasing the production of the anti-inflammatory cytokine interleukin-10, both of which play important roles in the pathogenesis of sepsis. The aim of this study was to examine the effects of bicuculline methiodide on sepsis in the cecal ligation and puncture septic-rat model. Cytokine production was measured by enzyme-linked immunosorbent assay. Oxidative stress was assessed by determining serum lipid peroxidation and nitrite levels. Hepatic injury was evaluated by determining the levels of serum aspartate aminotransferase, alkaline phosphatase, and total bilirubin. Mortality was recorded within 24 h. Bicuculline methiodide potently decreased the production of tumor necrosis factor-alpha and interleukin-1beta but increased interleukin-10 in serum. Bicuculline methiodide significantly decreased serum lipid peroxidation and nitrite levels. Further, bicuculline methiodide attenuated hepatic injury and reduced mortality after cecal ligation and puncture. Therefore, the alteration of cytokine production may be involved in the effects of bicuculline methiodide on hepatic injury and mortality in septic rats.
Hsu
Dur-Zong
DZ
Department of Environmental and Occupational Health, and Institute of Basic Medical Sciences, Medical College, National Cheng Kung University, Tainan 704, Taiwan.
Liu
Ming-Yie
MY
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001663:Bilirubin / Q000097:blood; D016207:Cytokines / Q000097:blood*; D018756:GABA Antagonists / Q000494:pharmacology*; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009573:Nitrites / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D018756:GABA Antagonists; D007375:Interleukin-1; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C017069:bicuculline methiodide; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; D001663:Bilirubin; D001640:Bicuculline