Valentovic M A, Ball J G
Department of Pharmacology, Marshall University School of Medicine, Huntington, West Virginia, USA.
J Toxicol Environ Health A. 1998 Oct 9;55(3):225-40. doi: 10.1080/009841098158511.
This study examined differences in toxicity between 2- and 4-aminophenol using a renal cortical slice model. Renal cortical slice toxicity for 2- and 4-aminophenol was also monitored in tissue from Sprague-Dawley and Fischer 344 (F344) rats in order to determine potential strain differences for aminophenol toxicity. Renal cortical slices from Sprague-Dawley and F344 rats (age 50-65 d) were isolated and incubated for 15-120 min with 0-1 mM 2- or 4-aminophenol at 37 degrees C under an oxygen atmosphere. Elevations in lactate dehydrogenase (LDH) leakage from renal cortical slices occurred at lower concentrations of 4-aminophenol than of 2-aminophenol from both strains of rats. Total glutathione levels were more markedly decreased by 4-aminophenol than by 2-aminophenol in renal slices from both strains. LDH release was elevated by 1 mM 2-aminophenol in renal slices from F344 rats, but values were comparable between control and treated in the renal slices from Sprague-Dawley rats. 4-Aminophenol was slightly more toxic to renal slices from F344 than from Sprague-Dawley rats. LDH release was increased, relative to controls, by 0.1 mM in the F344 rats group compared to 0.25 mM in the Sprague-Dawley group. Strain differences were not apparent when comparisons were made of total glutathione levels or rate-limiting substrates of gluconeogenesis. These results indicated that strain differences in toxicity were detected between Sprague-Dawley and F344 rat strains. Based on LDH release, renal cortical slices obtained from age-matched F344 rats were slightly more susceptible than Sprague-Dawley rats to toxicity by 2- and 4-aminophenol.
本研究使用肾皮质切片模型检测了2-氨基苯酚和4-氨基苯酚之间的毒性差异。为了确定氨基苯酚毒性的潜在品系差异，还监测了来自斯普拉格-道利大鼠和费希尔344（F344）大鼠组织中2-氨基苯酚和4-氨基苯酚的肾皮质切片毒性。从斯普拉格-道利大鼠和F344大鼠（年龄50-65天）分离出肾皮质切片，并在37℃、氧气氛围下与0-1 mM的2-氨基苯酚或4-氨基苯酚孵育15-120分钟。两种品系大鼠的肾皮质切片中，4-氨基苯酚浓度较低时，乳酸脱氢酶（LDH）泄漏量的升高幅度就高于2-氨基苯酚。两种品系大鼠的肾切片中，4-氨基苯酚使总谷胱甘肽水平降低的程度比2-氨基苯酚更明显。1 mM的2-氨基苯酚使F344大鼠肾切片中的LDH释放量升高，但斯普拉格-道利大鼠肾切片中对照组和处理组的值相当。4-氨基苯酚对F344大鼠肾切片的毒性略高于对斯普拉格-道利大鼠肾切片的毒性。与对照组相比，F344大鼠组中0.1 mM的4-氨基苯酚使LDH释放量增加，而斯普拉格-道利大鼠组中为0.25 mM。当比较总谷胱甘肽水平或糖异生的限速底物时，品系差异不明显。这些结果表明，在斯普拉格-道利大鼠和F344大鼠品系之间检测到了毒性的品系差异。基于LDH释放量，年龄匹配的F344大鼠的肾皮质切片比斯普拉格-道利大鼠对2-氨基苯酚和4-氨基苯酚的毒性更敏感。
