Manganese and iron species in Sprague–Dawley rats exposed with MnCl2∙ 4H2O (i.v.)

Abstract

Chronic manganese exposure leads to accumulation in brain mainly in the basal ganglia. Continuous incorporation finally causes neural damage (Manganism, Mn-PD) with disease pattern comparable to idiopathic Parkinson's disease (I-PD). Obviously, Mn is transported by an active mechanism across the blood–brain barrier (BBB) into the brain, but the exact transport mechanism is still not completely understood. The transferrin receptor shuttle is involved but it seems that this is not the only mechanism. Excretion of Mn follows slow simple diffusion. The exact transport mechanism is still unknown. Mn-metabolism involves a multiplicity of Mn species specifically affecting Mn-homeostasis. Low molecular mass (LMM) Mn species potentially facilitate Mn accumulation in brain.Therefore, this paper investigated the formation and distribution of Mn- and Fe-Species in vivo (Sprague–Dawley rats) after a single intravenous (i.v.) injection of a non-toxic dose of MnCl2∙4H2O. Speciation analysis used a specifically developed sample preparation under cryogenic conditions and was performed with size exclusion chromatography online coupled to inductively coupled plasma-mass spectrometry (SEC-ICP-MS). The sample preparation method was previously shown to maintain species stability at enhanced extraction efficiency. One hour after i.v. injection overload of native Mn-carriers (Mn–transferrin) and formation of LMM Mn species, eluting at the retention time (RT) of Mn–citrate, were found in serum. After four days, serum and feces seemed to be Mn-cleared, but brain and kidney showed significantly elevated Mn levels. Even in lung and muscle tissue Mn was increased, but to a smaller extent. Accumulation of Mn especially in brain and kidney originated from increased concentrations of inorganic Mn and Mn bound to LMM Mn species. Iron status and iron species pattern appeared to be completely unaffected from i.v. injected Mn. The results underlined that specifically LMM-Mn-compounds permeated the BBB and accumulated in brain and kidney. It is discussed that kidney may play a regulatory role in the homeostasis of LMM Mn species.