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Human & Experimental Toxicology
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In vitro and in vivo studies on chelation of manganese

P Missy

M-C Lanhers

Laboratoire de Chimie et de Toxicologie des Metaux, Département Environnement et Santé Publique, Faculté de Médecine, Université Henry Poincaré, Nancy I, Vandoeuvre-lès-Nancy, France

Y Grignon

Laboratoire d'Anatomie Pathologique, Faculté de Médecine, Université Henry Poincaré, Nancy I, Vandoeuvre-lès-Nancy, France

M Joyeux

SERES, Département Environnement et Santé Publique, Faculté de Médecine, Université Henry Poincaré, Nancy I, Vandoeuvre-lès-Nancy, France

D Burnel

Laboratoire de Chimie et de Toxicologie des Metaux, Département Environnement et Santé Publique, Faculté de Médecine, Université Henry Poincaré, Nancy I, Vandoeuvre-lès-Nancy, France

This work deals with new chelating agents of manganese (Mn).

Out of 24 compounds chosen for their chemical structure supposed to be favorable for Mn complexation, six polyaminopolycarboxylic acids proved to be efficient for displacing Mn bound to serum bovine proteins in vitro: TTHA, DTPA, DPTA, DPTA – OH, HBED, EDTA (mobilization>50%).

The first five compounds were then tested in vivo on rats pretreated with MnC12. They exhibited only slight to moderate efficacy to diminish Mn in tissues and were ineffective on increased Mn concentration in whole blood; in addition, they had different and specific mobilizing effects on other essential elements (Fe, Zn, Cu).

Their limited efficacyin vivo could be due to the formation of very stable complexes between Mn2+ and different molecules such as hemoglobin and certain cytochromes, instead of Fe2+. This could disturb the functioning of the cellular respiratory chain, leading to an incomplete reduction of 02 with formation of free oxygenated radicals, reduction in the energy supply, and disturbance of the cytochromes renewal mechanism. All of these phenomena could accelerate cellular aging and explain the lack of efficacy ofthe chelating agents towards Mn neurotoxicity (Parkinson's syndrome).

Key Words: manganese • intoxication • chelating agents • cellular respiratory chain • free oxygenated radicals • Parkinson's syndrome

Human & Experimental Toxicology, Vol. 19, No. 8, 448-456 (2000)
DOI: 10.1191/096032700682694260
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