NEPHROTOXICITY IN RATS UNDERGOING A ONE-HOUR EXPOSURE TO COMPOUND-A
NEPHROTOXICITY IN RATS UNDERGOING A ONE-HOUR EXPOSURE TO COMPOUND-A
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DOI：
10.1097/00000539-199509000-00024
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发表时间：
1995-09-01
影响因子：
5.7
通讯作者：
MARTIN, J
中科院分区：
文献类型：
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作者：
KANDEL, L;LASTER, MJ;MARTIN, J
我们之前证明，当大鼠暴露于 50 ppm 或更多的称为化合物 A [CF2 = C(CF3)OCH2F] 的乙烯基醚（一种由 CO2 吸收剂作用于七氟烷时产生的化合物）3-12 小时后会出现肾损伤。这些暴露持续时间超过了临床麻醉的平均持续时间。现在，我们报告了 145 只 Wistar 大鼠在氧气中暴露于 0、100、150、200、400、600 或 800 ppm 化合物 A 1 小时的影响。暴露后二十四小时，我们获得了肾脏和肝脏标本进行显微镜检查，应用苏木精和曙红，以及（单独）用于细胞增殖（再生）的免疫化学标记物（PCNA）。与对照大鼠（呼吸氧气 1 小时）的结果相比，肾损伤（定义为外髓层外带坏死或“皮质髓质连接坏死”）在 200 ppm 及以上发生。暴露于 150 ppm 会产生细胞再生（即刺激细胞增殖）。我们得出的结论是，暴露于化合物 A 1 小时的肾毒性阈值浓度（即最小毒性）超过临床实践中报告的最大浓度（特别是低流入速率时的浓度）2-3 倍。如果大鼠中的这些阈值效应适用于人类，那么接触七氟烷 1 小时可能不会改变肾功能的常规测量值。
We previously demonstrated that rats experienced renal injury when exposed for 3-12 h to 50 ppm or more of a vinyl ether called Compound A [CF2 = C(CF3)OCH2F], a compound produced by CO2 absorbents acting on sevoflurane. These durations of exposure exceed the average duration of clinical anesthesia. We now report the effect of a 1-h exposure to 0, 100, 150, 200, 400, 600, or 800 ppm of Compound A in oxygen in 145 Wistar rats. Twenty-four hours after exposure, we obtained kidney and liver specimens for microscopic examination, applying hematoxylin and eosin, and (separately) an immunochemical marker (PCNA) for cell proliferation (regeneration). Compared with results from control rats (those breathing oxygen for 1 h), renal injury (defined as necrosis of the outer strip of the outer medullary layer or ''corticomedullary junction necrosis'') occurred at and above 200 ppm. Exposure to 150 ppm produced cell regeneration (i.e., stimulated cell proliferation). We conclude that the threshold concentrations for nephrotoxicity (i.e., minimal toxicity) for a 1-h exposure to Compound A exceed the maximum concentrations (particularly those at low inflow rates) reported in clinical practice by a factor of 2-3. If these threshold effects in rats apply to humans, one 1-h exposure to sevoflurane probably would not alter usual measures of renal function.