METHYLENE DIANILINE - ACUTE TOXICITY AND EFFECTS ON BILIARY FUNCTION
METHYLENE DIANILINE - ACUTE TOXICITY AND EFFECTS ON BILIARY FUNCTION
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DOI：
10.1016/0041-008x(92)90221-d
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发表时间：
1992-11-01
影响因子：
3.8
通讯作者：
ANSARI, GAS
中科院分区：
文献类型：
--
作者：
KANZ, MF;KAPHALIA, L;ANSARI, GAS
用于聚合物工业的4，4 ′-亚甲基二苯胺（4，4 ′-二氨基二苯基甲烷，DAPM）可导致暴露人体的肝胆损伤。我们的目的是表征DAPM在肝脏中的急性毒性，特别是对胆汁成分分泌和胆汁上皮细胞γ-谷氨酰转肽酶（GGT）活性的影响。在戊巴比妥麻醉下，将胆管插管置于Sprague-Dawley雄性大鼠中。对照胆汁收集1小时后，每只大鼠口服250 mg DAPM/kg（50 mg/ml）溶于35%乙醇或仅溶于35%乙醇;再收集胆汁4小时。DAPM给药后4小时，主胆管细胞严重受损，外周胆管细胞损伤最小。24小时出现局灶性门静脉周围肝细胞坏死和皮质胸腺细胞广泛溶解。肝损伤的血清指标在4小时升高，并持续升高至24小时。4小时时，胆汁蛋白浓度增加4倍，而胆汁胆盐、胆红素和谷胱甘肽浓度分别下降80%、50%和200%。DAPM对胆汁葡萄糖也有显著影响，增加了20倍。DAPM后8小时，主胆管GGT组织化学染色不存在。胆汁流量减少了40%，在4小时，5只大鼠中有3只没有胆汁流量8小时，没有任何胆汁流量24 hr. These结果表明，DAPM迅速减少胆汁流量，改变胆汁成分的分泌，是高度有害的胆管上皮细胞。
4,4′-Methylene dianiline (4,4′-diaminodiphenylmethane, DAPM), which is used in the polymer industry, causes hepatobiliary damage in exposed humans. Our objectives were to characterize the acute toxicity of DAPM in liver, particularly on secretion of biliary constituents and on biliary epithelial cell γ-glutamyl transpeptidase (GGT) activity. Biliary cannulas were positioned in Sprague-Dawley male rats under pentobarbital anesthesia. After 1 hr of control bile collection, each rat was given 250 mg DAPM/kg (50 mg/ml) po in 35% ethanol or 35% ethanol only; bile was collected for a further 4 hr. Groups of rats were also examined for liver injury and biliary function at 8 and 24 hr after DAPM. Four hours after DAPM administration, main bile duct cells were severely damaged with minimal damage to peripheral bile ductule cells. Focal periportal hepatocellular necrosis and extensive cytolysis of cortical thymocytes occurred by 24 hr. Serum indicators of liver injury were elevated by 4 hr and continued to rise through 24 hr. By 4 hr, biliary protein concentration was increased 4-fold while concentrations of biliary bile salt, bilirubin, and glutathione were decreased by ∼80, 50, and 200%, respectively. DAPM also induced a striking effect on biliary glucose with an ∼ 20-fold increase. Histochemical staining of main bile duct GGT was absent by 8 hr after DAPM. Bile flow was diminished by 40% at 4 hr; three of five rats had no bile flow by 8 hr and none had any bile flow by 24 hr. These results indicate that DAPM rapidly diminishes bile flow and alters the secretion of biliary constituents and is highly injurious to biliary epithelial cells.