Chakrabarti S K, Tuchweber B
Médecine du Travail et Hygiène du Milieu, Faculté de Médecine, Université de Montréal, Québec, Canada.
Toxicology. 1987 Nov;46(3):343-56. doi: 10.1016/0300-483x(87)90214-9.
The effects of various inducers and inhibitors of hepatic microsomal mixed-function oxidase (MFO) system and diethylmaleate treatment on styrene-induced acute nephrotoxicity in male Fischer-344 rats were studied. Groups of rats were pretreated with either 3-methylcholanthrene (15 mg/kg, i.p., 3 days), or phenobarbital (80 mg/kg, i.p., 3 days), or SKF525-A (50 mg/kg, i.p., 1 h), or piperonyl butoxide (300 mg/kg, i.p., 2 h), or diethylmaleate (400 mg/kg, i.p., 90 min) prior to an i.p. administration of styrene (0, 0.6 and 0.9 g/kg) in corn oil. The uptake of p-aminohippurate (PAH) by renal cortical slices, the morphology of renal cortices, as well as urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma-GT) of control and pretreated rats were examined 24 h after styrene. The inducers and inhibitors of MFO system failed to modify further the acute nephrotoxicity of styrene. On the other hand, diethylmaleate pretreatment not only reduced further the uptake of PAH, but also produced further significant increase in the urinary excretion of NAG and gamma-GT observed at the higher dose of styrene. Similarly, ultrastructural studies showed a moderate increase in the severity of kidney damage induced at the higher dose of styrene due to pretreatment with diethylmaleate. These data suggest that tissue glutathione concentrations and hence, corresponding conjugating activity might be important determinants of styrene nephrotoxicity. The results further indicate that a metabolic activation system not involving certain cytochrome P-450 might be responsible in styrene-induced nephrotoxicity.
研究了肝微粒体混合功能氧化酶（MFO）系统的各种诱导剂和抑制剂以及马来酸二乙酯处理对雄性Fischer-344大鼠中苯乙烯诱导的急性肾毒性的影响。将大鼠分组，在腹腔注射玉米油中苯乙烯（0、0.6和0.9 g/kg）之前，分别用3-甲基胆蒽（15 mg/kg，腹腔注射，3天）、苯巴比妥（80 mg/kg，腹腔注射，3天）、SKF525-A（50 mg/kg，腹腔注射，1小时）、胡椒基丁醚（300 mg/kg，腹腔注射，2小时）或马来酸二乙酯（400 mg/kg，腹腔注射，90分钟）进行预处理。在苯乙烯处理24小时后，检测对照和预处理大鼠肾皮质切片对对氨基马尿酸（PAH）的摄取、肾皮质的形态以及N-乙酰-β-D-氨基葡萄糖苷酶（NAG）和γ-谷氨酰转肽酶（γ-GT）的尿排泄。MFO系统的诱导剂和抑制剂未能进一步改变苯乙烯的急性肾毒性。另一方面，马来酸二乙酯预处理不仅进一步降低了PAH的摄取，而且在较高剂量苯乙烯时观察到NAG和γ-GT的尿排泄进一步显著增加。同样，超微结构研究表明，由于马来酸二乙酯预处理，在较高剂量苯乙烯诱导的肾损伤严重程度有中度增加。这些数据表明组织谷胱甘肽浓度以及相应的结合活性可能是苯乙烯肾毒性的重要决定因素。结果进一步表明，不涉及某些细胞色素P-450的代谢激活系统可能与苯乙烯诱导的肾毒性有关。
