Effect of dexamethasone on NF-kB activation, tumor necrosis factor formation, and glucose dyshomeostasis in septic rats.
Glucocorticoids are potent anti-inflammatory and immunosuppressive therapeutic agents. The protective effect of dexamethasone (DEX) on hepatic phosphoenolpyruvate carboxykinase (PEPCK) transcript level, hepatic NF-kB (nuclear factor-kB) activation, and serum tumor necrosis factor alpha (TNF) formation was investigated in peritoneal sepsis induced by cecal incision in rats. For the control the rats were sham-operated with laparotomies only. Each group (N = 6) was pretreated with either normal saline (NS) or DEX before surgery (NS/Sham, NS/Sepsis, DEX/Sham, and DEX/Sepsis). At 3 hr post cecal incision, DEX treatment inhibited sepsis-induced hepatic NF-kB activation by 23%, suppressed circulating TNF by 50%, reduced serum glucose by 36%, reduced hepatic glycogen depletion by 76%, and attenuated PEPCK mRNA level. These findings suggested that DEX treatment was beneficial in attenuating glucose dyshomeostasis and significantly inhibited two sepsis-induced inflammatory mediators, NF-kB and TNF, in the early phase of peritoneal sepsis. However, in the late (6 hr) septic phase, DEX treatment inhibited serum TNF by 69%, but had no effect on NF-kB activation, glycogen depletion, and PEPCK mRNA level suggesting liver function failure injury.
Chang
C K
CK
Department of Surgery, Finch University of Health Sciences/The Chicago Medical School at Mount Sinai Hospital Medical Center, California Avenue at 15th Street, Chicago, Illinois 60608, USA.
Llanes
S
S
Schumer
W
W
D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000032:analysis; D015152:Blotting, Northern; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000032:analysis; D006706:Homeostasis; D008099:Liver / Q000737:chemistry; D008297:Male; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism; D015345:Oligonucleotide Probes / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D010538:Peritonitis / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism* / Q000502:physiology
D001786:Blood Glucose; D005938:Glucocorticoids; D016328:NF-kappa B; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D006003:Glycogen; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D005947:Glucose