Reduced brain Na+, K+-ATPase activity in rats with galactosamine-induced hepatic failure: relationship to encephalopathy and cerebral oedema.
Previously we have shown that sera from patients with fulminant hepatic failure (FHF) will inhibit partially purified rat brain Na+, K+-ATPase and sodium efflux from human leucocytes in vitro. Similar inhibition may be involved in the pathogenesis of encephalopathy and cerebral oedema in these patients. In the present study we have attempted to establish whether the activity of brain Na+, K+-ATPase is decreased in vivo in rats with D-galactosamine induced hepatic failure using homogenates of snap-frozen brains. Na+, K+-ATPase activity was significantly reduced in the forebrain region at the stage of mild encephalopathy (43 h after injection), while at the deeper stage of coma (43-53 h after injection) enzyme activity was further reduced in the forebrain region and was also significantly reduced in the hindbrain region. Ouabain insensitive ATPase activity was not significantly altered at any time. While a significant increase in the water content (0.5%) of the hindbrain region was found 43 h after galactosamine, there was no clear correlation between the development of cerebral oedema and the reduction of Na+, K+-ATPase activity. The activity of partially purified normal rat brain Na+, K+-ATPase was 15% lower when incubated with sera from rats in the deep stage of coma compared with control sera. These data support other evidence that the reduction in brain Na+, K+-ATPase is likely to be due to toxic substance circulating in serum which have been shown to inhibit this enzyme in vitro and to cause coma when administered to normal animals.
D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000201:enzymology*; D001929:Brain Edema / Q000201:enzymology* / Q000209:etiology; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000150:complications* / Q000209:etiology; D005688:Galactosamine; D006501:Hepatic Encephalopathy / Q000201:enzymology* / Q000209:etiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D005688:Galactosamine; D000254:Sodium-Potassium-Exchanging ATPase