Influence of Dietary Manganese on the Pharmacokinetics of Inhaled Manganese Sulfate in Male CD Rats

Abstract

Concerns exist as to whether individuals with relative manganese deficiency or excess may be at increased risk for manganese toxicity following inhalation exposure. The objective of this study was to determine whether manganese body burden influences the pharmacokinetics of inhaled manganese sulfate (MnSO(4)). Postnatal day (PND) 10 rats were placed on either a low (2 ppm), sufficient (10 ppm), or high (100 ppm) manganese diet. The feeding of the 2 ppm manganese diet was associated with a number of effects, including reduced body weight gain, decreased liver manganese concentrations, and reduced whole-body manganese clearance rates. Beginning on PND 77 +/- 2, male littermates were exposed 6 h/day for 14 consecutive days to 0, 0.092, or 0.92 mg MnSO(4)/m(3). End-of-exposure tissue manganese concentrations and whole-body (54)Mn elimination rates were determined. Male rats exposed to 0.092 mg MnSO(4)/m(3) had elevated lung manganese concentrations when compared to air-exposed male rats. Male rats exposed to 0.92 mg MnSO(4)/m(3) developed increased striatal, lung, and bile manganese concentrations when compared to air-exposed male rats. There were no significant interactions between the concentration of inhaled MnSO(4) and dietary manganese level on tissue manganese concentrations. Rats exposed to 0.92 mg MnSO(4)/m(3) also had increased (54)Mn clearance rates and shorter initial phase elimination half-lives when compared with air-exposed control rats. These results suggest that, marginally manganese-deficient animals exposed to high levels of inhaled manganese compensate by increasing biliary manganese excretion. Therefore, they do not appear to be at increased risk for elevated brain manganese concentrations.

Nutritional aspects of manganese homeostasis

“…For example, the concentration of Mn in the diet is known to influence the amount of Mn absorbed from the gastrointestinal tract as well as its elimination via the bile. Adaptive changes to high dietary Mn intake include reduced gastroin- Mn content 3-10 lg/l 30-50 lg/l 200-300 lg/l testinal tract absorption, enhanced liver metabolism, and increased biliary and pancreatic excretion of this metal (Britton and Cotzias, 1966;Davis et al, 1993;Dorman et al, 2001Dorman et al, , 2002Finley and Davis, 1999;Malecki et al, 1996). Mn absorption from the diet is also influenced by the presence of other trace minerals, phytate, ascorbic acid, and other dietary constituents (Davidsson et al, 1991).…”

Manganese-Enhanced Magnetic Resonance Imaging

“…These include the chemical form (79), the presence of other minerals and dietary constituents (33,80,81), and the age of the animal (82)(83)(84). Furthermore, adaptive changes to high dietary manganese intake lead to reduced absorption and enhanced hepatic (biliary) or pancreatic excretion of manganese (19,(85)(86)(87)(88).…”

Manganese Neurotoxicity

“…In general, the concentration of Mn in the diet influences the amount absorbed through GI tract as well as the amount which is eliminated in the bile. When dietary Mn levels are high, adaptive changes include reduced GI absorption, enhanced Mn liver metabolism, and increased biliary and pancreatic excretion of the metal (Dorman et al 2001. Additionally, several factors can influence Mn absorption and retention.…”

“…Under basal conditions, brain Mn concentrations are heterogeneous, with the highest values reported in the palladium and putamen in humans and in the hypothalamus in rats (Bird et al 1984;Dorman et al 2001). The basal ganglia accumulate the highest Mn levels upon excessive exposure to this metal, although the precise physiological basis for this result remains unclear.…”