Valentovic M A, Ball J G, Hong S K, Rogers B A, Meadows M K, Harmon R C, Rankin G O
Department of Pharmacology, Marshall University School of Medicine, 1542 Spring Valley Drive, Huntington, WV 25704-9388, USA.
Toxicol In Vitro. 1996 Dec;10(6):713-20. doi: 10.1016/s0887-2333(96)00060-4.
Chloroanilines have been associated with renal and hepatic toxicity. This study (a) examined the in vitro hepatic and renal toxicity of 2-chloroaniline and 4-chloroaniline, (b) further examined whether aromatic ring hydroxylation would increase toxicity of the parent compound and (c) compared toxicity between respective aminochlorophenol and aminophenol. Renal and hepatic slices were exposed to varying concentrations of 2-chloroaniline, 4-chloroaniline. 4-amino-3-chlorophenol, 2-amino-5-chlorophenol, 2-aminophenol or 4-aminophenol. Toxicity was monitored by measurement of pyruvate-directed gluconeogenesis and leakage of lactate dehydrogenase (LDH). Hepatic tissue was less susceptible to toxicity than kidney tissue for all compounds since LDH leakage was elevated only in renal tissue. Gluconeogenesis was reduced in renal cortical slices exposed to 0.1 mum aminochlorophenols or 4-aminophenol, whereas a concentration of 0.5 mum was necessary for the chloroanilines and 2-aminophenol. LDH release was increased in renal slices by aminochlorophenols and aminophenols but not by the chloroanilines. The nephrotoxic potential in renal cortical slices was 4-aminophenol > 2-amino-5-chlorophenol > 4-amino-3-chlorophenol > 2-aminophenol > 2-chloroaniline = 4-chloroaniline. These results suggest that aromatic ring hydroxylation increased in vitro toxicity of the chloroanilines. Comparison of aminophenols with aminochlorophenols indicated that addition of a halogen can have variable effects on toxicity.
氯苯胺与肾毒性和肝毒性有关。本研究（a）检测了2-氯苯胺和4-氯苯胺的体外肝毒性和肾毒性，（b）进一步检测了芳香环羟基化是否会增加母体化合物的毒性，以及（c）比较了相应的氨基氯苯酚和氨基酚之间的毒性。将肾切片和肝切片暴露于不同浓度的2-氯苯胺、4-氯苯胺、4-氨基-3-氯苯酚、2-氨基-5-氯苯酚、2-氨基酚或4-氨基酚中。通过测量丙酮酸导向的糖异生作用和乳酸脱氢酶（LDH）的泄漏来监测毒性。对于所有化合物，肝组织比肾组织对毒性更不敏感，因为LDH泄漏仅在肾组织中升高。暴露于0.1μm氨基氯苯酚或4-氨基酚的肾皮质切片中糖异生作用降低，而对于氯苯胺和2-氨基酚则需要0.5μm的浓度。氨基氯苯酚和氨基酚可增加肾切片中LDH的释放，但氯苯胺则不会。肾皮质切片中的肾毒性潜力为4-氨基酚＞2-氨基-5-氯苯酚＞4-氨基-3-氯苯酚＞2-氨基酚＞2-氯苯胺 = 4-氯苯胺。这些结果表明，芳香环羟基化增加了氯苯胺的体外毒性。氨基酚与氨基氯苯酚的比较表明，添加卤素对毒性的影响可能各不相同。
