Caffeine attenuates liver damage and improves neurologic signs in a rat model of hepatic encephalopathy.

INTRODUCTION AND AIMS: Cirrhosis is the common outcome of liver diseases. It can be decompensated and lead to the development of complications, such as encephalopathy. Hyperammonemia that develops due to liver dysfunction is etiopathologically related to hepatic encephalopathy. Caffeine increases the activity of the urea cycle in the liver, augmenting ammonia degradation. By antagonizing adenosine receptors, it also has a hepatoprotective effect, impeding the formation of fibrosis, as well as having a stimulating effect on the central nervous system. The present study analyzed the effects of caffeine on the progression of cholestatic liver fibrosis and hepatic encephalopathy. MATERIALS AND METHODS: An experimental model of cholestatic liver fibrosis, through common bile duct ligature, and of hepatic encephalopathy, through the administration of a high-protein diet, was constructed. Male Wistar rats (n=32) were equally divided into 4 groups. The experiment lasted 28 days, with the administration of 50mg/kg/day of caffeine. Laboratory tests, histologic analyses of the liver and encephalon, open field tests (OFTs), and daily behavioral analyses were carried out. RESULTS: The ligated animals treated with caffeine had lower mean transaminase levels and improved histologic aspects of the liver and encephalon. The untreated ligated animals were clearly lethargic and apathetic at the last week of the experiment, confirmed by reduced exploratory activity during the OFT. CONCLUSION: Caffeine improved the microarchitecture of the liver and encephalon of the cirrhotic animals and prevented the decrease in exploratory behavior of the animals during the OFT.

Calcium-potassium-stimulated net potassium efflux from human erythrocyte ghosts.

In the presence of 8 mM external Ca++, the K+ permeability of human red cell ghosts increases provided K+ is also present in the medium. This increase does not represent K+/K+ exchange but a stimulation of net K+ efflux. The stimulation is half-maximal at 0.7 +/- 0.15 mM (n=5). At concentrations above 4.0 mM, external K+ inhibits net K+ efflux. Similar stimulatory and inhibitory effects of external K were also observed in intact cells after exposure to Pb++ or to Ca++ in the presence of fluoride, iodoacetate plus adenosine, or propranolol, suggesting that a common K+ -activated K+ -specific transfer system may be involved under all of these various circumstances. Internal K+ also stimulates net K+ efflux from ghosts, but it is uncertain whether internal K+ is an absolute requirement for the K+ permeability increase. In contrast to external Na+ which slightly stimulates K+ efflux, internal Na+ inhibits. The inhibition by internal Na+ is abolished by sufficiently high concentrations of external K+, showing that K+ binding to the outer membrane surface and Na+ binding to the internal surface are mutually interdependent. In red cell ghosts the Ca++ -K+ -stimulated net K+ efflux increases with increasing pH until a plateau is reached between pH 7.2 and 8.0. In fluoride-poisoned intact cells, the Ca++-K+ stimulated flux passes through a maximum around pH 6.8. Neither internal nor external Mg++ interferes with the combined effects of Ca++ and K+. Similarly, external EDTA has no influence at concentrations which are far lower than the Ca++ concentration required to produce a maximal response. In contrast, low concentrations of internal EDTA prevent the permeability change.