In vitro and in vivo studies on chelation of manganese

This work deals with new chelating agents of manganese (Mn). Out of 24 compounds chosen for their chemical structure supposed to be Favo rable for Mn complexation. six polyaminopolycarboxylic acids proved to be e fficient for displacing Mn bound to serum bovine proteins in vitro: TTHA. D TPA. DPTA, DPTA-OH. HEED. EDTA (mobilization greater than or equal to 50% ) . The first Five compounds were then tested in vivo on rats pre treated with MnCl2. They exhibited only slight to moderate efficacy to diminish Mn in ti ssues and were ineffective on increased hin concentration in whole blood: i n addition, they had different and specific mobilizing effects on other ess ential elements (Fe. Zn. Cu). Their limited efficacy in vivo could be due to the formation of very stable complexes between Mn2+ and different molecules such as hemoglobin and cert ain cytochromes, instead of Fe2+. This could disturb the functioning of the cellular respirator?; chain. leading to an incomplete reduction of O-2 wit h formation of free oxygenated radicals, reduction in the energy supply, an d disturbance of the cytochromes renewal mechanism. All of these phenomena could accelerate cellular aging and explain the lack of efficacy of the che lating agents towards Mn neurotoxicity (Parkinson's syndrome).