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Abstract

On the basis of reports that astrocytes play an important role in the neurotoxicity of trimethyltin (TMT), we investigated the sensitivity of astrocytes to TMT and compared it to triethyltin (TET), a neurotoxic analog with a different in vivo specificity. The gliotoxicity of these two compounds was further compared to that of tributyltin (TBT) and triphenyltin (TPT), two purportedly nonneurotoxic organotin compounds. The time and concentration components of organotin toxicity were determined by measuring lactate dehydrogenase (LDH) release and formazan production from dimethylthiazolyldiphenyltetrazolium bromide (MTT). A TMT concentration of 100 micromol/L did not elevate extracellular LDH until 48 h after exposure, while signs of toxicity were not seen at 72 h for concentrations less than 10 micromol/L. Extracellular LDH activity increased 24 h after exposure to concentrations of TET, TBT, and TPT as low as 2.5 micromol/L. TMT was the only organotin to produce a delayed cytotoxicity, requiring both higher concentrations and more time to produce discernible toxicity. In contrast with TBT and TPT, the toxicity of the two neurotoxic organotins (TMT and TET) produced an early increase in MTT reduction. The distinct pattern of toxicity for TMT does not explain its selective in vivo toxicity, but the lack of sensitivity of astrocytes to this organotin also does not rule out more subtle changes in these cells that could disrupt normal glial/neuronal interactions.

Toxic effect of triphenyltin onLemna polyrhiza

“…4 TPT and triphenyltin (TBT) are known to be immunotoxic and cause renal and hepatic damage; the relative order of organotin toxicity in astrocyte cultures is TPT > TBT. 5 Organotins (TPT and TBT) directly inactivate cytochrome P-450 because of interaction with critical sulfhydryl groups of the hemoprotein, and TBT is metabolized more readily than TPT in rat, hamster and human. 6 The IC 50 s of TPT to hepatic glutathione Stransferase activity in marine fish Siganus canaliculatus and Sparus sarba are 10 and 28 µM, respectively.…”

Dealkylation of Organotin Compounds by Biological Dithiols: Toward the Chemistry of Organotin Toxicity

“…showed that the extent of this dealkylation correlates inversely with the length and stability of alkyl chains. Furthermore, delayed toxic action of polysubstituted organotins has been observed and associated with the rate of in vivo conversion of highly substituted organotins into their metabolites. , Organotin dealkylation has also been detected in the environment, where alkyl group removal has been attributed to the action of UV light, chemical cleavage, and biological degradation by bacteria. Although the chemistry of organotin degradation has never been elucidated, organotin reactivity has been attributed to the nature of the C−Sn bond that can be attacked by both nucleophilic and electrophilic reagents …”

Boswellic Acid Improves Cognitive Function in a Rat Model Through Its Antioxidant Activity

“…As mentioned in the results, lipid peroxidation returned to near control levels in the B80 and the B160 groups. On the other hand, a major antioxidant, which protects cells against oxidative stress, is GSH [ 28 ]. Exposure to TMT induces oxidative stress, which decreases the GSH levels and reflects the degree of oxidative insult.…”