ACUTE EXPOSURE TO CADMIUM CAUSES SEVERE LIVER-INJURY IN RATS
ACUTE EXPOSURE TO CADMIUM CAUSES SEVERE LIVER-INJURY IN RATS
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DOI：
10.1016/0041-008x(82)90013-8
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发表时间：
1982-01-01
影响因子：
3.8
通讯作者：
KLAASSEN, CD
中科院分区：
文献类型：
--
作者：
DUDLEY, RE;SVOBODA, DJ;KLAASSEN, CD
在大鼠静脉注射3.9 mg Cd/kg（LD 99）的急性心脏毒性进行了研究。镉染毒后9 h开始间断记录心电图、血压和心率，直至死亡。未观察到心脏指数变化。主要组织的显微镜检查显示组织学正常的心肌，但严重受损的肝脏。为了进一步评价镉的肝毒性作用，时间过程（3.9 mg Cd/kg，i. v. 0.9- 3.9mg Cd/kg，i.v.进行了研究。检查肝脏的组织病理学变化;测定天冬氨酸（ADT）和丙氨酸（ALT）转氨酶和碱性磷酸酶（AP）的血浆酶活性，以评估肝损伤。CD后1 h内出现明显的嗜酸性粒细胞增多、肝细胞肿胀和肝细胞有丝分裂象增加。还观察到AST和ALT活性增加，但AP活性和血糖浓度不变。随后，肝细胞坏死、血清酶（AST、ALT和AP）显著升高和血糖浓度降低50%证明了重度肝损伤。剂量-反应数据表明，> 1.1 mg Cd/kg的剂量产生的病理变化类似于3.9 mg Cd/kg后1 h的时程研究中观察到的病理变化。> 3.5 mg Cd/kg剂量可引起肝脏大面积坏死，ALT、AST和AP活性分别增加60、100和3倍。在> 2.9 mg Cd/kg的剂量下也观察到血糖浓度降低50%。这些结果并不表明，镉是心脏毒性急性暴露后，而是肝脏是急性镉毒性的主要靶器官。
The acute cardiotoxicity of Cd was studied in rats injected i.v. with 3.9 mg Cd/kg (LD99). ECG, blood pressure and heart rate were recorded intermittently from 9 h after Cd administration until death. No changes were observed in cardiac indices. Microscopic examination of the major tissues revealed histologically normal myocardium but severely damaged liver. To evaluate further the observed hepatotoxic effects of Cd, time course (1-10 h after 3.9 mg Cd/kg, i.v.) and dose-response (10 h after 0.9-3.9 mg Cd/kg, i.v.) studies were conducted. Liver was examined for histopathologic changes; plasma enzyme activities of aspartate (ADT) and alanine (ALT) aminotransferases and alkaline phosphatase (AP) were determined to assess liver damage. Pronounced eosinophilia, hepatocyte swelling and an increase of mitotic figures in heptaocytes were present within 1 h after Cd. Increased AST and ALT activities were also observed, but AP activity and plasma glucose concentration were unchanged. At later times, severe liver injury was evidenced by necrosis of hepatocytes, striking elevation of serum enzymes (AST, ALT and AP), and a 50% decrease in plasma glucose concentration. Dose-response data indicated that doses > 1.1 mg Cd/kg produced pathologic changes similar to those observed in the time course study 1 h after 3.9 mg Cd/kg. Doses > 3.5 mg Cd/kg caused massive hepatic necrosis and increased ALT, AST and AP activities 60-, 100- and 3-fold, respectively. A 50% decrease in plasma glucose concentration was also observed at doses > 2.9 mg Cd/kg. These results did not suggest that Cd was cardiotoxic after acute exposure, but rather that the liver was a major target organ for acute Cd toxicity.