水銀中毒に関する研究 (Hg Series No.5) : ジチオール剤とくにチオクト酸の水銀解毒効果について
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Ueda and his co-workers have recently reported that thioctic (TA) (lipoic acid), especially dihydro-thioctic acid (DTA) combined with mercury in vitro to form a non-toxic substance, and later Ishii and Shimizu proved their detoxicating effect by animal experiment. But in the field experiments with workers in aclinical thermometer factory and with other operators exposed to mercury, the distinct promotion of mercury excretion in urine was hardly observed as Shimizu's paper reported. From these results it became necessary to reinvestigate the detoxicating effect of TA by more detailed experiments. Part 1: Effect on urinary mercury excretion in rabbits. Rabbits were injected intramusc. 0.2mg/kg of mercury (as HgCl_2) for twelve days, and then BAL (dimercaptol-propanol) or OTA in peanut oil was injected for three succesive days. In the BAL group the mercury excretion in urine was promptly increased three to five times, whereas in the DTA group the increase was only one and a half to two times of that in the pre-experimental period. Mono-thiol agents were also investigated and L-cysteine and DL-penicillamin showed promoting effects as excellent as BAL. The ineffectiveness of DTA on the mercury excretion in urine might be understood if the resultant compound in the body for a long time due to its poor solubility. To assertain this point, SS'-mercuri-TA was prepared in vitro and injected to rabbits intramusc. The result was in support of the author's assumption, and no increase of mercury excretion was observed during a week. Part 2: Effect of dithiol-agents on the growth of rats poisoned with mercury. (a) A dilute solution of mercuric nitrate (Hg 30ppm) was given to rats ad lib. from water bottles through 30 days. The antidote was injected intramusc. dalily. The growth curve of DTA group (10mg/kg) was as good as BAL group (6mg/kg), but both were inferior to the healthy control. In the case of high mercury dosing (100 ppm) DTA could show a remarkable detoxicating effect whereas TA could not support the growth after 18 days. (b) The previous experiment had rather a prophylactic nature because the detoxicant and poison were given simultaneously from the start. In order to investigate the therapeutic effect, the rats were first poisoned with 250ppm mercury for ten days. The animal lost the weight drastically reaching the initial level of two weeks before. Then BAL or DTA was given intramusc. daily. The recovery was dramatical and the growth rate was practically equal in these two antidotes. (c) The organ-body weight ratio of liver and kidney was investigated in the experiment (a) mentioned above. The BAL group showed hardly any difference in the ratios compared with the control, but in DTA and non-treated groups the ratios were significantly higher than the control, indicating the enlargement of organs. (d) The brain, liver and kidney of rats in the experiment (a) were assayed for the mercury content. The BAL group was excellent only one to one and a half times of mercury being found as compared with that of the healthy control. DTA group was also good though slightly inferior to BAL group and only one-fourth of mercury deposit was found compared with the non-treated group. These results indicated the gradual transportation and excretion of SS'-mercuri-TA in spite of its poor solubility in body fluid. As for the route of excretion, the possibility through the digestive tract including the biliary might be considered as suggested in the previous paper of Shimizu using S^<35>-TA in experimental mercury poisoning. Conclusion; DTA was able to detoxicate mercury in the experimental chronic poisoning in rats and rabbits. As the resultant product is insoluble in water, the prompt increase of urinary excretion of mercury is hardly expected. This is the difference from other thiol-agents and the evaluation of effects by the urinary assay will be misleading in this instance. Mercury combined with DTA is fixed and harmless and gradually excr
- 社団法人日本産業衛生学会の論文
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