Rita M. Nelson

The formation of chlorobenzene and benzene by the reductive metabolism of lindane in rat liver microsomes.

The major metabolite produced by incubating [14C]lindane with rat liver microsomes under anaerobic conditions was determined to be chlorobenzene, with lesser amounts of benzene also being formed. Using relatively high lindane concentrations (250 microM), four nonvolatile metabolites of lindane were also produced anaerobically, the predominant one being identified by mass spectrometry as tetrachlorocyclohexene (TCCH). TCCH, likewise, was reduced to chlorobenzene and benzene in microsomes under anaerobic conditions. Binding of [14C]lindane to microsomal protein occurred under aerobic as well as anaerobic incubation conditions; however, lindane protein binding was greatest in anaerobic incubations compared to those containing an atmosphere of air or 100% oxygen. Hemin reduced by dithionite also readily produced chlorobenzene and benzene from lindane. These results indicate that lindane interacts readily with heme and heme proteins, including cytochrome P-450, in the absence of oxygen to undergo multiple chloride eliminations forming chlorobenzene and benzene as end products.

Elevated ornithine decarboxylase activity in the rat liver following exposure to halothane, enflurane and isoflurane☆

Exposure of rats to the volatile anesthetics, halothane, enflurane and isoflurane and low FIO2 (0.8%) for two hours results in a transient induction of ODC appearing maximally four hours after exposure. Without the low oxygen accompanying the anesthetic or the low oxygen alone, no significant induction of ODC occurred. The concentration of anesthetic used to produce the ODC induction were 0.5% halothane, 1.5% enflurane and 1.4% isoflurane. Except for halothane, reducing the anesthetic concentration only slightly reduced the effect on ODC levels to control values. Reduction of halothane concentrations to 0.1% was required to reduce the values to control levels. Pretreatment of the animals with either cycloheximide or actinomycin D delayed the onset of ODC induction. The data support the fact that liver damage can occur in the absence of metabolism of the drug.