Inhibition of rat brain Na+,K+-ATPase activity by serum from patients with fulminant hepatic failure

Abstract

Among the toxins accumulating in the circulation of patients with fulminant hepatic failure (FHF) are substances which inhibit leucocyte ouabain-sensitive sodium transport. A similar inhibition of brain Na+,K+-ATPase could lead to both coma and cerebral edema found in these patients which are associated with high mortality. In this study, we have investigated the effect of sera from FHF on normal rat brain Na+,K+-ATPase activity in vitro. Serum from patients with FHF significantly decreased the ouabain-sensitive Na+,K+-ATPase activity (13.58 +/- S.D. 2.60 mumoles Pi mg protein-1 hr-1) in the rat brain membrane preparation in vitro as compared to normal serum (20.33 +/- 3.24 mumoles Pi mg protein-1 hr-1, p less than 0.001). A final serum dilution of 1 in 40 was required to abolish the inhibition of Na+,K+-ATPase activity. Cerebrospinal fluid obtained at postmortem from FHF patients also contained the inhibitory substances. Serum from patients in coma due to decompensated chronic liver disease inhibited the Na+,K+-ATPase activity (17.25 +/- 1.37 mumoles Pi mg protein-1 hr-1), but this was less marked than with FHF serum. Hence, the inhibition of brain Na+,K+-ATPase by substances accumulating in the serum in FHF may be important in the pathogenesis of hepatic coma.