水銀, 카드뮴, 鉛이 白鼠의 肝의 N-Demethylase 活性에 미치는 影響

Abstract

現代産業의 發達과 農藥, 殺蟲劑, 化學物質, 治療劑 等의 使用增加로 有害 重金屬에 對한 露出이 날로 加重되고 있다. 一般的으로 金屬은 生物의 生理機能을 維持하는데 必要한 物質로 酵素의 助成 및 活性觸媒로 代謝에 重要 役割을 한다. 그러나 水銀, 카드뮴, 鉛과 같은 重金屬은 化學的으로 各種의 有機配位子와 結合體를 形成하여 肝, 腎臟, 腦 等에 蓄積되어 生理機能을 妨害한다. 이중에서 肝은 生體內에서 解讀作用을 主宰하는 器官이므로, 本實驗에서는 水銀, 카드뮴, 鉛을 重金屬으로 擇하고, 이들이 肝의 代謝過程中 microsome酸化에 關與하는 N-demethylase의 活性에 미치는 影響을 檢索할 目的으로 쥐를 使用하여, 大量 單回投與時와, 7日, 14日, 21日間의 少量 反復投與時와, 鉛投與 後 ascorbic acid 投與時 肝의 N-demethylase 活性을 觀察하여 다음과 같은 結果를 얻었다. A. 大量 單回投與時 카드뮴 投與群 및 鉛投與群에서 肝의 N-demethylase 活性이 對照群에 比하여 各各 顯著하게 44.9%, 32.5% 減少하였다. 水銀投與群은 實驗中 쥐가 死亡하여 結果를 얻지 못하였다. B. 少量 反復投與時 1. 體重은 7日, 14日, 21日로 時間이 經過함에 따라, 對照群은 正常的으로 體重이 增加한데 반하여, 水銀, 카드뮴, 鉛을 投與한 後는 體重이 減少하는 傾向을 보였다. 즉, 水銀投與群에서는 7日後에 急激하게 體重이 減少되었고, 카드뮴 投與群에서는 14日과 21日사이에 顯著한 體重의 減少를 나타내었으며, 鉛投與群에서는 14日까지는 體重의 變化가 거의 없었으나 그후부터는 增加하는 傾向을 나타내었다. 2. 肝의 N-demethylase活性은 水銀投與群에서는 7日, 14日, 21日로 經過함에 따라 對照群에 比하여 各各 5.7%, 27.1%, 27.7% 減少되었으며, 카드뮴 投與群에서는 各各 13.1%. 23.6%, 36.0%의 減少率을 나타내었고, 鉛投與群에서는 15.3% 減少하였다가 14日, 21日後에 各各 33.4%, 23.2% 減少하였다. C. 鉛化合物을 大量 單獨으로 投與한 때는 N-demethylase의 活性이 32.5% 減少한데 반하여, 鉛化合物을 大量 單回投與後 ascorbic acid를 投與한 때는 13.1% 減少하여, 19.4%의 補償效果를 나타내었다. 水銀과 카드뮴 化合物을 大量 單回投與한 後는 쥐가 死亡하여 結果를 얻지 못하였다. 以上의 結果로 수은, 카드뮴, 鉛化合物은 쥐 肝의 N-demethylase活性을 減少시키며, ascorbic acid는 鉛化合物로 因한 쥐 肝의 N-demethylase 活性 抑制에 對하여 補償效果를 나타내는 것으로 思料된다.;In order to investigate the effect of mercury, cadmium, and lead on N-demethylase activity of rat liver, such metals were administrated by intraperitoneal injection to rats as follows: 5mg of HgCl_(2), 10mg of CdCl_(2), and 100mg of Pb(Ac)_(2) per kilogram of body weight to observe the acute toxicities and 1.5mg of HgCl_(2), 1.0mg of CdCl_(2), and 3.0mg of Pb(Ac)_(2) per day kilogram of body weight to see the chronic toxicities. Animals were sacrificed at the 3rd day of metal administration for the experiment of acute toxicity and the 7th, the 14th, and the 21st day for that of chronic toxicity. Aminopyrine was used as the substrate of N-demethylase reaction of the microsomal oxidase and the amount of formaldehyde yielded by the reaction was quantitated by Nash reagent. The results obtained from the experiments were as follows: 1. In the experiments of Cd and Pb for their acute toxicities to rats, the activity of N-demethylase was reduced to 55.1% and 67.5% of the control group for Cd and Pb, respectively. 2. In the experiments of Hg, Cd, and Pb for their chronic toxicities to rats, the reduction of body weight of rats was observed throughout the whole experimental period. Interestingly, three metals showed different reduction patterns of body weights, i.e., body weight was drastically reduced by Hg, within 7 days and began to compensate its loss thereafter, in case of Cd, a sudden decrease of body weight was observed between 14 days and 21 days, and body weight did not change upto 14 days after administration of Pb and then showed a gradual increase, while the control group gradually increased its weight along with time. The activity of N-demethylase in rat liver was gradually reduced upto 21 days after administration of Hg, Cd, and Pb, as compared with those of the control group. The reduction of the enzyme was 27.7% by Hg, 36.0% by Cd, and 23.2% by Pb on the 21st day. 3. When ascorbic acid was given to the rats treated with Pb(Ac)_(2), the activity of N-demethylase was partially recovered, for instance, 86.9% of N-demethylase activity in the group given ascorbic acid as well as Pb, while 67.5% of the enzyme activity of the group treated with Pb alone without ascorbic acid administration. as compared with that of the control group. The groups of rats given either Hg or Cd were expired within a day after metal administration, thus, it was not possible to conduct the experiment of ascorbic acid effect on N-demethylase. In summary, the HgCl_(2), CdCl_(2), and Pb(Ac)_(2) caused the reduction of N-demethylase activity in rat liver and the activity of N-demethylase reduced by Pb(Ac)_(2) was recovered to a certain extent by administrating ascorbic acid.