Meeting Abstract
P1.180 Friday, Jan. 4 Chelating Agents Reverse Neurotoxic Effects of Manganese on Dopaminergic Innervation of Gill of the Bivalve Mollusc Crassostrea virginica OJO, C.*; ROGERS, K.; ADAMS, T.; CATAPANE, E.J.; CARROLL, M.A.; Medgar Evers College; Medgar Evers College; Medgar Evers College; Medgar Evers College; Medgar Evers College catapane@mec.cuny.edu
Lateral cilia of gill of Crassostrea virginica are controlled by a serotonergic-dopaminergic innervation. Dopamine is an inhibitory transmitter at gill causing cilio-inhibition. Manganese (Mn)is a neurotoxin causing Manganism in people exposed to high levels in the atmosphere. Clinical interventions for Manganism have not been successful. Recently, p-aminosalicylic acid (PAS) was reported to provide effective treatment of severe Manganism in humans. PAS is an anti-inflammatory drug which has been used to treat tuberculosis. It also has chelating properties. Previously, we showed treatments of C. virginica with Mn disrupts dopaminergic innervation of gill. Pre- or co-treatments with PAS or calcium disodium EDTA prevented the neurotoxic effects of Mn. We hypothesized chelating agents would be effective in reversing neurotoxic effects of Mn when applied to gills after Mn. We used gills of C. virginica to measure lateral cilia beating rates of preparations treated first with Mn followed by treatments with either PAS, calcium disodium EDTA or DMSA (meso-2,3-dimercaptosuccinic acid). Beating of cilia were measured by stroboscopic microscopy. Dose responses of PAS, calcium disodium EDTA and DMSA (10-11 – 10-4 M) against beating were conducted after 100 µM of Mn was added to gill. All 3 drugs reversed the neurotoxic effects of Mn in a dose-dependent manner. DMSA was the most potent. The study demonstrates these chelators are effective in reversing acute neurtoxicity of manganese. This information should be of interest to those designing therapeutic drug treatments for Manganism.
