Study on the biological effect by arsenic exposure to acute arsenic poisoning patient, especially to embryo and newbaby.

砷暴露对急性砷中毒患者尤其是胚胎和新生儿的生物学效应研究。

• 批准号: 11470100
• 负责人: YAMAUCHI Hiroshi
• 金额: $ 2.69万
• 依托单位: St.Marianna University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470100/
• 关键词: acute arsenic poisoning; embryo; newbaby; brain damage; DNA damage; apoptosis; methylation; behavioristics

We investigated the relationship between acute exposure to arsenic trioxide during the fetal period and the occurrence of brain damage in the fetus and childhood. We gave a single oral administration of arsenic trioxide to pregnant rats at the 17th day of gestation and observed the changes in arsenic concentration in the brains of the fetuses and mother rats at 12 to 48 hr after administration. Compared with the control, a marked rise in arsenic concentration was recognized in the exposed group fetuses. Arsenic concentration in the fetal brains (inorganic arsenic and its metabolites) was three times higher than that of the control at 12 to 48 hr after administration. The dynamics of the chemical specis of the arsenic detected in the fetal brains were : concentration of inorganic arsenic was rising at 12 hr after administration, but at every time point, what was rising mainly was dimethylated arsenic (DMA), the final metabolite of arsenic trioxide, in the fetal brains. Histopathological examination was carried out on the mother rats and fetuses. No apoptosis or necrosis was recognized in the brains of the mother rats. Neither was necrosis recognized in the fetal brains. In contrast to this, appearance of apoptotic cells was clearly recognized in the fetal brains at 12, 24 and 48 hr after administration of arsenic trioxide. Detection of apoptotic cells in the fetal brains was most marked in the 12 hr group. The results of this study show clear brain tissue damage in cases of exposure to relatively high doses of inorganic arsenic in the fetal period, and this suggests possible future brain damage as squeal.We thought that the generation of the cerebral disorder by the arsenic exposure of the embryo period was suggested in a behavioristics inspection result of the organization diagnosis, and would have the necessity which was the enough development by the research of this field in the future in this research.

我们研究了胎儿期急性三氧化二砷暴露与胎儿和儿童期脑损伤发生的关系。我们在妊娠第17天给孕鼠单次口服三氧化二砷，观察给药后12 ~ 48小时胎鼠和母鼠脑内砷浓度的变化。与对照组相比，暴露组胎儿的砷浓度明显升高。在给药后12至48小时，胎儿脑中的砷浓度（无机砷及其代谢物）比对照组高3倍。胎儿脑内检测到的砷的化学形态动态为：在给药后12小时，无机砷浓度呈上升趋势，但在各时间点，上升的主要是三氧化二砷的最终代谢物二甲基化砷（DMA）。对母鼠和胎鼠进行组织病理学检查。母鼠脑内未见细胞凋亡或坏死。胎儿大脑中也未发现坏死。与此相反，三氧化二砷给药后12、24和48小时，胎儿大脑中凋亡细胞的出现被清楚地识别出来。胎儿大脑中凋亡细胞的检测在12小时组最为明显。这项研究的结果清楚地表明，在胎儿期暴露于相对高剂量的无机砷的情况下，脑组织会受到损伤，这表明未来可能出现的脑损伤是尖叫。我们认为胚胎期砷暴露导致脑障碍的发生在组织诊断的行为学检查结果中得到了提示，并且本研究具有未来该领域研究足够发展的必要性。

项目成果

Yuko Nito, Kou Sakabe, Hiroshi Yamauchi, Hiroyuki Aikawa, Katsumi Yoshida: "Fetal Brain Damage Induced by Acute Arsenic Poisoning in Pregnancy in Rats."Biomed Res Trace Elements. 11(3). 300-305 (2000)

Yuko Nito、Kou Sakabe、Hiroshi Yamauchi、Hiroyuki Aikawa、Katsumi Yoshida：“妊娠期急性砷中毒引起的胎儿脑损伤。”Biomed Res 微量元素。

仁藤裕子,坂部貢,山内博,相川浩幸,吉田勝美: "急性砒素中毒の妊娠ラットの胎仔における脳障害の研究"Biomed Res Trace Elements. 11・3. 300-305 (2000)

Yuko Nito、Mitsugu Sakabe、Hiroshi Yamauchi、Hiroyuki Aikawa、Katsumi Yoshida：“急性砷中毒妊娠大鼠胎儿脑损伤的研究”Biomed Res Trace Elements 11・3（2000）。

仁藤裕子,坂部貢,山内博,相川浩幸,吉田勝美: "急性ヒ素中毒の妊娠ラットの胎仔における脳障害の研究"Biomed Res Trace Elements. 11・3. 300-305 (2000)

Yuko Nito、Mitsugu Sakabe、Hiroshi Yamauchi、Hiroyuki Aikawa、Katsumi Yoshida：“急性砷中毒妊娠大鼠胎儿脑损伤的研究”Biomed Res Trace Elements 11・3（2000）。

Hiroshi Yamauchi and Yukio Yamamura: "Acute Arsenic Poisoning."Medical Practice. 17(9). 1539-1541 (2000)

Hiroshi Yamauchi 和 Yukio Yamamura：“急性砷中毒”。医疗实践。

山内博: "哺乳動物における砒素代謝"Biomed Res Trace Elements. 11・1. 25-34 (2000)

山内浩：“哺乳动物中的砷代谢”Biomed Res Trace Elements 11・1（2000）。