INFLUENCE OF THE ROUTE OF ADMINISTRATION AND THE CHEMICAL FORM [MNCL2, MNO2) ON THE ABSORPTION AND CEREBRAL DISTRIBUTION OF MANGANESE IN RATS

The absorption and cerebral distribution of manganese (Mn) have been s tudied with respect to the route of administration and the chemical fo rm of the Mn compound. Different groups of adult male rats received ei ther MnCl2 . 4H(2)O or MnO2 once a week for 4 weeks at a dose of 24.3 mg Mn/kg body wt. (b.w.) by oral gavage (g.) or 1.22 mg Mn/kg b.w. by intraperitoneal injection (i.p.) or intratracheal instillation (i.t.). Control rats were treated with 0.9% saline. Four days after the last administration the rats were killed and the concentration of Mn measur ed in blood, hepatic and cerebral tissues (cortex, cerebellum, and str iatum). The liver Mn concentration was not affected by the treatments whatever the chemical form or the route of administration of the Mn co mpound. Administration of MnCl2 by g., i.p., and i.t. routes produced equivalent steady-state blood Mn concentrations (about 1000 ng Mn/100 mi), representing increases of 68, 59, and 68% compared with controls, respectively. Mn concentrations were significantly increased in the c ortex but to a lesser extent (g., 22%; i.p., 36%; i.t., 48%) and were higher in the cerebellum after i.p. and i.t. administrations than afte r oral gavage. Rats treated i.t. with MnCl2 showed an elective increas e of the striatal Mn concentration (205%). In contrast, MnO2 given ora lly did not significantly increase blood and cerebral tissue Mn concen trations; the low bioavailability is most likely due to the lack of in testinal resorption. Administration of MnO2 i.p. and i.t., however, le d to significant increases of Mn concentrations in blood and cerebral tissues. These increments were not significantly different from those measured after MnCl2 administration, except for striatal Mn after i.t. which was markedly less (48%) after MnO2 administration. A comparison of the blood Mn kinetics immediately after g. and i.t. treatment with MnCl2 or MnO2 indicated that the higher elevation of blood Mn concent ration (> 2000 ng Mn/100 mi) after i.t. administration of MnCl2 could account for the elective uptake of Mn in the striatum observed in repe ated dosing experiments. It is concluded that the modulation of Mn dis tribution in brain regions according to the route of administration an d the chemical form of the Mn compound may be explained on the basis o f different blood Mn kinetics and regional anatomic specificities of t he striatal region.