A Comparative Study on Reductive Dehalogenation of Halothane in Liver, Kidney and Lung of the Rabbit

The contents of cytochrome P-450 (P-450) and cytochrome b5, and the activity of NADPH-cytochrome c reductase and the reductive metabolites of halothane, 2-chloro-1, 1-difluoroethylene (CDE) and 2-chloro-1, 1, 1-trifluoroethane (CTE) were measured in microsomes from the liver, kidney and lung of phenobarbital (PB) pretreated and untreated Japanese white strain rabbits. Microsomal P-450 levels in the liver, kidney (renal cortex) and lung of the rabbits were 1.91 ± 0.35, 0.19 ± 0.04 and 0.42 ± 0.11 nmol/mg protein (mean ± SD), respectively. In vivo phenobarbital pretreatment (PB-pretreatment) increased the content of P-450 to 2.95 ± 0.40 nmol/mg protein (154%) in the liver and to 0.40 ± 0.11 nmol/mg protein (211 %) in the kidney, but had little effect in the lung. The activity of CDE formation was 0.72 ± 0.10, 0.08 ± 0.04 and 0.03 ± 0.01 nmol/mg protein/ min in the liver, kidney and lung, respectively. PB-pretreatment enhanced the activity of CDE formation to 1.59 ± 0.49 nmol/mg protein (221 %) in the liver, and to 0.29 ± 0.16 nmol/mg protein/min (363%) in the kidney, but showed little enhancement in the lung. The activity of CTE formation was 1.30 ± 0.19, 0.12 ± 0.04 and 0.09 ± 0.02 nmol/mg protein/min, in the liver, kidney and lung, respectively. PB-pretreatment enhanced the activity of CTE formation to 1.80 ± 0.44 nmol/mg protein/min (138%) in the liver, but caused only slight enhancement in the kidney and lung. PB-pretreatment markedly enhanced the activity of CDE formation in the kidney. The authors conclude that cytotoxicity by reductive dehalogenation of halothane is possible not only in the liver but also in the kidney with PB-pretreatment.This study was supported in part by a Research Grant from the Japanese Ministry of Education, Science and Culture