In vitro neurotoxicity of methyl iodide

Histopathologic Approaches to Chemical Toxicity Using Primary Cultures of Dissociated Neural Cells Grown in Chamber Slides

“…In our laboratory, murine cerebrocortical cell cultures have served successfully as a model for elucidating mechanisms of chemically induced neurotoxicity using several biochemical and pharmacological endpoints (2,3,(5)(6)(7). Our work also suggests that morphologic criteria, including intracellular accumulation of vital dyes (5) Light Microscopy. Culture morphology was assessed qualitatively in live cultures using phase-contrast microscopy both before and after toxicant exposure (3,5).…”

“…Our work also suggests that morphologic criteria, including intracellular accumulation of vital dyes (5) Light Microscopy. Culture morphology was assessed qualitatively in live cultures using phase-contrast microscopy both before and after toxicant exposure (3,5). Subsequently, culture morphology and antigen expression at the &dquo;tissue&dquo; and cellular levels were evaluated in fixed, stained cultures by brightfield microscopy.…”

Acute methyl iodide exposure with delayed neuropsychiatric sequelae: Report of a case

“…Addition of sulfasalazine or semicarbazide, both powerful inhibitors of glutathione-S-transferase, to the test system did not alter the pattern of neurocytotoxic effect [Bonnefoi et al, 1991]. Furthermore, while depletion of mitochondrial glutathione correlated with neural cell injury, measured by lactate dehydrogenase leakage at 24 hr, cell death was not directly dependent on depletion of cytosolic glutathione [Davenport et al, 1992]. In a further set of experiments, depletion of the glutathione pool prior to the reaction with methyl iodide greatly exacerbated the cytotoxicity of methyl iodide as measured by neural cell loss.…”

“…Several in vitro studies have concluded that glutathione depletion alone leads to neurotoxicity [Bonnefoi et al, 1991;Bonnefoi, 1992;Davenport et al, 1992;Chamberlain et al, 1999].…”

“…Proposed mechanisms of toxicity include the direct cytotoxic effect of the intact compound itself or toxicity due to one of its metabolites [Bonnefoi et al, 1991;Bonnefoi, 1992;Davenport et al, 1992]. Direct methylation of cellular macromolecular protein components by these compounds may play a role in their toxicity .…”