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二氯苯异构体对Fischer 344大鼠的急性肝肾毒性

Acute hepatic and renal toxicity of dichlorobenzene isomers in Fischer 344 rats.

作者信息

Valentovic M A, Ball J G, Anestis D, Madan E

机构信息

Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25755-9310.

出版信息

J Appl Toxicol. 1993 Jan-Feb;13(1):1-7. doi: 10.1002/jat.2550130103.

Abstract

Studies were conducted to examine acute hepatic and renal toxicity of dichlorobenzene (DCB) structural isomers. Male Fischer 344 (F344) rats were injected with 2, 3 or 4 mmol kg-1 of 1,2-DCB, 1,3-DCB or 1,4-DCB (o-, m-, p-). Pair-fed control (PFC) animals were injected (i.p.) with corn oil (1 ml kg-1). Hepatic and renal toxicity was quantitated 24 h after injection of DCB or vehicle. Plasma transaminase (ALT/GPT) activity was increased (P < 0.05) by 1,2-DCB as a function of dose administered. Centrilobular necrosis was observed in rats treated with 1,2-DCB while morphology was relatively normal in rats treated with m- or p-DCB. Administration of (2 or 4 mmol kg-1) 1,3-DCB or 1,4-DCB did not alter kidney weight or blood urea nitrogen (BUN) levels. Renal cortical slice accumulation of p-aminohippurate (PAH) was decreased (P < 0.05) by (2 and 4 mmol kg-1) 1,3-DCB and (3 and 4 mmol kg-1) 1,2-DCB while accumulation of the cation tetraethylammonium (TEA) was decreased by 4 mmol kg-1 1,4-DCB. (TEA). The results of these studies demonstrated that ortho substitution enhanced hepatic and renal toxicity. The results also would suggest that the liver was more sensitive than the kidney for DCB toxicity.

摘要

开展了多项研究以检测二氯苯(DCB)结构异构体的急性肝毒性和肾毒性。给雄性Fischer 344(F344)大鼠注射2、3或4 mmol kg-1的1,2-二氯苯、1,3-二氯苯或1,4-二氯苯(邻位、间位、对位)。配对喂饲对照(PFC)动物经腹腔注射玉米油(1 ml kg-1)。在注射DCB或赋形剂24小时后对肝毒性和肾毒性进行定量分析。随着1,2-二氯苯给药剂量的增加,血浆转氨酶(ALT/GPT)活性升高(P < 0.05)。在接受1,2-二氯苯治疗的大鼠中观察到小叶中心坏死,而接受间位或对位二氯苯治疗的大鼠形态相对正常。给予(2或4 mmol kg-1)1,3-二氯苯或1,4-二氯苯不会改变肾脏重量或血尿素氮(BUN)水平。(2和4 mmol kg-1)1,3-二氯苯和(3和4 mmol kg-1)1,2-二氯苯可降低对氨基马尿酸(PAH)在肾皮质切片中的蓄积(P < 0.05),而4 mmol kg-1 1,4-二氯苯可降低阳离子四乙铵(TEA)的蓄积。这些研究结果表明,邻位取代增强了肝毒性和肾毒性。结果还表明,肝脏对二氯苯毒性的敏感性高于肾脏。

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