EFFECT OF BILIARY LIGATION ON MANGANESE ACCUMULATION IN RAT-BRAIN

Neurologic and radiologic disorders have been reported to occur in min ers inhaling manganese (Mn)-laden dust and in humans receiving long-te rm parenteral nutrition. These abnormalities have been attributed to M n intoxication because of elevated serum Mn concentrations. Because th e liver, by way of the bile, is the major route of Mn excretion, it is possible that anything that decreases biliary excretion could increas e accumulation of Mn in the brain. The purpose of this study was to de termine whether biliary ligation would increase Mn accumulation in the brain of rats that were exposed to deficient or adequate amounts of d ietary manganese. The first experiment had a 2 x 3 factorial design, t wo levels of Mn (0 or 45 mu g/g diet) and three surgical treatments (c ontrol, sham, or bile-ligation). Animals were sacrificed 10 d after be ing fed Mn-54. In experiment 2, animals that had a sham operation or b ile-ligation were sacrificed at 8 time points after being injected int raportally with 54Mn complexed to albumin. The biliary-ligated animals had a significantly (p < 0.001) smaller percentage of the 54Mn in the ir brains (when expressed as a percentage of whole animal 54Mn) than t he sham-operated animals. Mn deficiency had a similar effect. However, we did observe an increased accumulation of the radioisotope in the b rain over time. Therefore, in short-term studies, biliary-ligated rats do not appear to be a good model for Mn accumulation in the brains of people with cholestatic liver disease.