Thiamine deficiency as one of the mechanisms for neurotoxicity induced by lead intoxication in rats.

In this study, it was tested whether lead intoxication could change thiamine content and the thiamine related biochemical factor such as activity of transketolase in the brain, and whether the changes of the myelin composition :s well as the seizure threshold induced by lead intoxication in rats be related to these changes of thiamine status and thiamine related biochemical factors. In addition, it was also tested whether administration of excessive thiamine can reverse the toxic manifestation of lead in lead intoxicated animals. Five groups of Wistar rats were prepared: 1)Control group, 2)lead treated group, 3)thiamine treated group, 4)lead plus thiamine treated group and 5)thiamine deficiency group. Each group of animals was divided into three subgroups based on ages: 3, 7 and 10 weeks of age subgroups. Lead concentration, thiamine content, the activity of transketolase and myelin composition in brain areas and threshold of electric shock seizure were tested in each group. Lead concentrations in all brain regions of lead treated group were higher than those of control group, and those of lead plus thiamine treated group were significantly lower than those of lead treated group. Thiamine contents in the brain regions of lead treated group were significantly lower than those of control group, and those of lead plus thiamine treated group were recovered back to those of control group. Activities of transketolase of lead treated group were significantly lower than those of control group, while those of lead plus thiamine treated group were recovered back to those of control group. The cases of which was observed with the concomitant changes of thiamine content and transketolase activity in myelin content or constituent of all the brain regions tested were total amount of myelin protein in the cerebellum of 3 week old rats, and phospholipid in the cerebellum of 3 week old rats and the telencephalon of 16 week old rats. Thresholds of the electroshock seizure of lead-treated group and thiamine-deficient group in 3, 7 week old rats were significantly lower than those of control group, while those of the lead plus thiamine-treated group were similar to those of control group. Changes of the electroshock seizure threshold induced by lead intoxication were observed in 3 week and 7 week old animals with the concomitant decrement of thiamine content in all the brain regions tested. These observations were reversed by the supplementation with thiamine to those animals. However, the changes of seizure threshold induced by lead intoxication corelated with the changes of thiamine contents as well as. transketolase due to lead intoxication. The changes of myelin phospholipid as one of myelin composition and those of myelin Protein content only in the cerebellum of 3 week old rats correlated with the changes of the seizure threshold as well as thiamine content due to lead intoxication. The results from the present study may indicate that neurotoxicity of lead in rats may be mediated at least in part through the changes of thiamine status. Such changes of thiamine status may induce the changes of myelin composition such as myelin phospholipid and those of myelin protein content especially in the cerebellum of 3 week old rats which may eventually affect the threshold of seizure.