Neurotoxic effects of bismuth in vitro

Although insoluble bismuth (Bi) salts are known to be neurotoxic, recently interest in oral Bi therapy has been renewed because of encouraging results obtained in the treatment of gastritis and peptic ulcer associated with Helicobacter pylori infection. For risk assessment of orally administered Bi preparations it is important to determine the minimal neurotoxic Bi concentration in the brain. This concentration was determined in cultures of brain, meninges and neuronal retina cells from embryonic chicks and in cultures of hippocampal slices from rats. Cytotoxicity, as assessed by neutral red uptake, thiazolylblue tetrazoliumbromide dehydrogenase activity and morphological criteria, occurred at Bi concentrations (about 10 mum) comparable with those that have been observed in humans and mice with Bi-induced encephalopathy. Regional differences of Bi effects on astrocytes, assessed by expression of glial fibrillary acidic protein, were observed in cell cultures of the embryonic chick brain. Measurement of expression of microtubular-associated protein type 2 indicated that astrocytes were much more sensitive to Bi than were nerve cells. Therefore it seems that astrocytes are an important target of Bi toxicity, and this would explain the reversibility of signs and symptoms of Bi encephalopathy on cessation of therapy. Acute exposure of cultured rat brain slices to Bi had no effect on the bioelectric activity of hippocampal pyramidal cells, whereas chronic exposure produced neuronal degeneration.