Assessment of bioaccumulation and neurotoxicity in rats with portacaval anastomosis and exposed to manganese phosphate: A pilot study

The use of the additive methylcyclopentadienyl manganese tricarbonyl in unl eaded gasoline has resulted in increased attention to the potential toxic e ffects of manganese ( Mn). Hypothetically, people with chronic liver diseas e may be more sensitive to the adverse neurotoxic effects of Mn. In this wo rk, bioaccumulation of Mn, as well as histopathology and neurobehavioral da mage, in end-to-side portacaval anastomosis ( PCA) rats exposed to Mn phosp hate via inhalation was investigated. During the week before the PCA operat ion, 4 wk after the PCA operation, and at the end of exposure, the rats wer e subjected to a locomotor evaluation ( day-night activities) using a compu terized autotrack system. Then a group of 6 PCA rats ( EXP) was exposed to 3050 mug m(-3) ( Mn phosphate) for 8 h/day, 5 days/wk for 4 consecutive wee ks and compared to a control group ( CON), 7 PCA rats exposed to 0.03 mug m (-3). After exposure, the rats were euthanized and Mn content in tissues an d organs was determined by neutron activation analysis. The manganese conce ntrations in blood (0.05 mug/g vs. 0.02 mug/g), lung (1.32 mug/g vs. 0.24 m ug/g), cerebellum (0.85 mug/g vs. 0.64 mug/g), frontal cortex (0.87 mug/g v s. 0.61 mug/g), and globus pallidus (3.56 mug/g vs. 1.33 mug/g) were signif icantly higher in the exposed group compared to the control group (p < .05) . No difference was observed in liver, kidney, testes, and caudate putamen between the two groups. Neuronal cell loss was assessed by neuronal cell co unts. The loss of cells in globus pallidus and caudate putamen as well as i n frontal cortex was significantly higher (p < .05) for the EXP group. Asse ssment of the locomotor activities did not reveal any significant differenc e. This study constitutes a first step toward our understanding of the pote ntial adverse effects of Mn in sensitive populations.