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Abstract
Intraperitoneal administration of the volatile hydrocarbon, naphthalene, resulted
in severe bronchiolar epithelial cell necrosis in mice, while hepatic or renal necrosis
was not observed. Pulmonary damage and mortality by naphthalene were increased by
prior treatment with diethyl maleate and decreased by prior treatment with piperonyl
butoxide (1600 mg/kg). SKF 525A pretreatment had no effect on naphthalene-induced
pulmonary damage. Administration of [14C]naphthalene resulted in the covalent binding
of radiolabel to tissue macromolecules. Highest levels of binding occurred in lung,
liver and kidney. Levels of covalent binding reached a maximum 2--4 h after treatment
and corresponded to rapid glutathione depletion in lung and liver. Covalent binding
was dose-dependent and showed a threshold between 200 and 400 mg/kg which coincided
with almost total depletion of tissue glutathione levels. Covalent binding of reactive
metabolites was increased 3--4-fold by prior treatment with diethyl maleate, and was
decreased 3--4-fold by pretreatment with piperonyl butoxide. These studies support
the view that naphthalene-induced pulmonary damage is mediated by the cytochrome P-450-dependent
metabolism of naphthalene and that glutathione plays an important role in the detoxification
of the lung damaging metabolite(s).