Abstract
Electroencephalographic (EEG) studies were conducted to demonstrate the ameliorating effects of lactitol and its reference drug lactulose on the disturbance of consciousness caused by severe hepatic encephalopathy in rats permanently implanted with cortical electrodes. A novel experimental animal model of combined-type human hepatic encephalopathy was prepared by portacaval shunting followed by a single treatment with dimethylnitrosamine (30 mg/kg, i.p.). Lactitol or lactulose was orally administered twice a day for seven days and once on the morning of the eighth day. Ammonium acetate (500 mg/kg) was injected into the cecum 4 hr after the final administration of the drug. In control animals not treated with either drug, but in which hepatic encephalopathy had been induced, ammonium acetate induced a comatose state defined by a loss of the righting reflex accompanied by slowing or flattening of the cortical EEG. In control animals, significant increases in delta (1-3 Hz)-activity and significant decreases in beta (1325 Hz)-activity during coma were detected by means of EEG power spectral analysis. Lactitol at doses of 3 g/kg/day or higher or lactulose at 6 g/kg/day significantly suppressed these EEG changes. Both drugs also suppressed in a dose-dependent manner the loss of the righting reflex. Lactitol may therefore be useful for ameliorating the disturbance of consciousness in patients with hepatic encephalopathy.
