The influence of glucocorticoids on hepatic glycolytic intermediates in fed peritonitis rats.
Earlier work on fasted endotoxemic and septic rats suggested that glucocorticoid pretreatment improved survival by promoting gluconeogenesis. The possible mechanism of this therapeutic effect was investigated in fed peritonitis septic rats, which are in a predominantly glycolytic mode of metabolism. Fed adult male rats (185-255 g) received cecal incisions or sham operations under ether with or without simultaneous IV injection of dexamethasone (DMS) (1.0 mg/100 g rat). Liver was sampled by freeze-clamping at 5 h, and glycolytic intermediates were determined by UV spectrophotometry. The high-energy intermediate, phosphoenol-pyruvate (PEP), fell 57% to 76 +/- 83 nmole/g wet liver (+/- 1 SD) in the fed peritonitis group; nine of 13 rats had PEP values at least 50% below mean control concentrations. Fasted septic rats (N = 26) do not have decreased PEP levels. Glucocorticoids were protective in the fed septic rats; only five of 17 DMS-pretreated rats had PEP fall below 50% of the fed normals. A significant finding was the decline in fructose diphosphate (FDP) from 32 +/- 9 nmole in fed shams (N = 12) to 21 +/- 11 nmole/g wet liver with DMS-pretreated fed shams (N = 15). This suggests that DMS may be inhibiting the glycolytic enzyme, phosphofructokinase, and thereby enhancing gluconeogenesis by sparing hexose monophosphates. Lactate in fed sham liver was 1,869 +/- 336 nmole/g, a concentration twofold greater than in fasted liver. This difference may contribute to the increased vulnerability of fed rats to septic shock. It is concluded that glucocorticoids tend to normalize Embden-Meyerhof pathway intermediates in both fed and fasted rat livers.
D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005502:Food; D005635:Fructosediphosphates / Q000032:analysis; D006019:Glycolysis / Q000187:drug effects*; D006600:Hexosephosphates / Q000032:analysis; D007773:Lactates / Q000032:analysis; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010538:Peritonitis / Q000188:drug therapy / Q000378:metabolism*; D010728:Phosphoenolpyruvate / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000378:metabolism
D005635:Fructosediphosphates; D006600:Hexosephosphates; D007773:Lactates; C004180:dexamethasone 21-phosphate; D010728:Phosphoenolpyruvate; D003907:Dexamethasone