Chelating agents reverse neurotoxic effects of manganese on dopaminergic innervation of gill of the bivalve mollusc Crassostrea virginica

Abstract

Lateral gill cilia of Crassostrea virginica are controlled by a serotonin‐dopamine (DA) innervation. DA is an inhibitory transmitter at gill causing cilio‐inhibition. Manganese (Mn) is a neurotoxin causing Manganism in people exposed to high levels in air. Clinical interventions for Manganism have not been successful. Recently, p‐aminosalicylic acid (PAS) was reported to provide effective treatment of Manganism. PAS is an anti‐inflammatory drug with chelating properties. We showed treatments of C. virginica with Mn disrupts DA innervation of gill. Pre‐or co‐treatments with PAS or EDTA prevented it. We hypothesized chelating agents would be effective in reversing neurotoxic effects of Mn when applied 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, EDTA or DMSA (meso‐2,3‐dimercaptosuccinic acid). Dose responses of PAS, EDTA and DMSA (10−11–10−4M) against beating were conducted after 100 FM 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 Mn. This information should be of interest to those designing therapeutic drug treatments for Manganism. Supported by 2R25GM06003 of NIGMS, 0516041171 of NYSDOE and 0622197 of NSF.