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Inhibition of partially purified rat brain Na+, K+-dependent ATPase by bile acids, phenolic acids and endotoxin.

Sera from patients with fulminant hepatic failure (FHF) has previously been shown to contain substance(s) which inhibit leucocyte ouabain-sensitive sodium efflux and rat brain Na+, K+-dependent ATPase in vitro. Similar effects in the patients could be an important mechanism in the development of encephalopathy and cerebral oedema. In previous studies, bilirubin, free fatty acids and mercaptans have been shown to inhibit Na+, K+-ATPase in vitro. The present report is concerned with the effects of a number of other potentially toxic substances present in the serum of patients with FHF. Chenodeoxycholic acid, p-hydroxyphenyllactic acid, p-hydroxyphenylpyruvic acid and endotoxin caused 30-45% inhibition of partially purified rat brain Na+, K+-ATPase at concentrations known to occur in the serum of patients with FHF. At low concentrations the inhibitory effects of these substances were additive, but at higher concentrations a maximum level of inhibition was reached. These further substances are likely, therefore, to be of importance in the disturbances of brain function found in FHF.