Efficacy of glucocorticoids in preventing mitochondrial metabolic failure in endotoxemia.
Endotoxemia was induced in rats and guinea pigs by an intraperitoneal injection of E coli endotoxin. In the rat, the dose used (3 mg/100 g body weight) resulted in a 60% mortality in 24 h. The same dose in the guinea pig resulted in a similar mortality at 24 h, and a 100% mortality by 3 days. Methylprednisolone Na-succinate, a glucocorticoid, given simultaneously with the endotoxin, prevented mortality in the rats. No animals died during the observation period. In the guinea pigs the same treatment protected all animals for 24 h, and resulted in an 80% survival rate over a 6-day observation period. Administration of glucocorticoids 1 or 2 h after endotoxin showed diminished efficacy. About 60% of the guinea pigs died during the 6-day observation period. Rat kidney and guinea pig brain and kidney mitochondria were isolated and analyzed for their function in untreated and treated animals 24 h after the injection of endotoxin. Rat kidney mitochondrial O2 utilization and ATP synthesis function, as well as Ca++ transport activity, were significantly below normal in the untreated animals, but did not differ from normal in glucocorticoid-treated animals. In untreated and at zero time treated guinea pigs similar results were found in brain and kidney mitochondrial functions. If treatment was delayed for 1 or 2 h, however, brain mitochondrial O2 utilization and ATP synthesis rates were significantly below normal, and both brain and kidney mitochondrial Ca++ transport capacities remained significantly lowered. The data support the efficacy of early glucocorticoid treatment in endotoxemia. Early glucocorticoid treatment prevents the deterioration of brain and kidney mitochondrial function.
D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D005938:Glucocorticoids / Q000494:pharmacology*; D006168:Guinea Pigs; D007668:Kidney / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats; D014115:Toxemia / Q000378:metabolism*
D004731:Endotoxins; D005938:Glucocorticoids; D002118:Calcium