Tributyltin–sulfhydryl interaction as a cause of immunotoxicity in phagocytes of tunicates

We reported elsewhere that tributyltin (TBT) has detrimental effects on the immune system of the colonial ascidian Botryllus schlosseri, through interaction with calmodulin and alteration of Ca2+ homeostasis. Here, we studied the capability of TBT to react with intracellular thiols. After exposure to 0.1 μM TBT, a significant decrease in B. schlosseri hemocytes stained for total thiols and reduced glutathione (GSH) was detected. Exogenous sulfhydryl and sulfide compounds can prevent TBT-induced cell morphology alterations and decrease the percentage of tin-containing hemocytes, indicating the scavenging ability of thiol peptides. No effects were observed with disulfides, N-acetylcysteine, or the GSH fragment Cys-Gly. No interactions were observed with TBT and carmustine, whereas TBT and N-ethylmaleimide (NEM) showed a combined antagonistic action, suggesting direct interaction of TBT with thiol-containing compounds. Regulation of Ca2+ efflux from internal stores seems to depend on stimulation of the inositol 1,4,5-trisphosphate (InsP3) receptor by oxidized glutathione (GSSG), which results from interactions of both TBT-GSH and TBT-GSH reductase.