PREVENTION OF ENDOTOXIN-INDUCED CHANGES IN OXIDATIVE-PHOSPHORYLATION IN HEPATIC MITOCHONDRIA

  • 1 January 1977
    • journal article
    • research article
    • Vol. 82  (1) , 68-73
Abstract
Escherichia coli endotoxemia affects hepatic energy linked function by uncoupling oxidation from phosphorylation. This study was done to determine whether a steroid, methylprednisolone sodium succinate (MPS), as well as excess substrate sodium succinate (SS), directly alters the effects of endotoxin on hepatic mitochondria. An assay system using .alpha.-ketoglutarate (.alpha.-Kg) was developed to test this hypothesis. Isolated rat hepatic mitochondria were first incubated in concentrations of MPS, ranging from 2.0-6.0 mg/ml. At these concentrations uncoupling identical to that occurring with addition of endotoxin resulted. However, a more dilute solution of MPS, 0.12 mg/ml, permitted normal mitochondrial function. Preincubation of MT in 0.12 mg/ml of MPS, as well as with sodium succinate, prevented endotoxin-induced uncoupling. Both endotoxin and steroid resulted in increased ATPase activity in the medium. While preincubation with MPS blocks the endotoxin effect, very high steroid concentrations alone are harmful. A direct action of steroids on mitochondria is evident, as well as a weaker protective effect due to excess substrate (.alpha.-Kg + SS). Since mitochondria are probably in direct communication with extracellular fluid, the assay system permits interaction of endotoxin, steroids and substrates which mimic those which occur in vivo.

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