Cumene hydroperoxide-mediated lipid peroxidation in rat alveolar macrophages following induction of phospholipidosis with chlorphentermine.

Rats were treated for 4 weeks with chlorphentermine hydrochloride (30 mg/kg, i.p., 5 days/seek), a regimen which causes a profound phospholipidosis in the alveolar macrophages (AMs). The susceptibility of these lipid-laden cells to lipid peroxidation was examined and compared to AMs from control (untreated) rats. Lipid peroxidation was induced in cells in vitro by incubation with cumene hydroperoxide (10(-5) M--10(-3) M). A dose dependent increase in malonyl dialdehyde (MDA) formation was observed with both populations of AMs. Two to three times more MDA was found in lipidotic AMs than controls at the higher dose of cumene hydroperoxide. Under these conditions, less loss of cellular viability resulted with the lipidotic AMs than controls. The partial depletion of reduced glutathione in the cells led to an even greater MDA formation by both cell-types with the lipidotic AMs being more markedly affected. Both populations of AMs experienced a greater loss of viability associated with loss of reduced glutathione with the control AMs showing more toxicity than the lipidotic cells. Therefore, while the induction of phospholipidosis renders AMs more suspectible to lipid peroxidation, they show less of a loss in cellular viability than control cells. The previously reported augmentation in the antioxidant defense mechanisms in the lipidotic cells may be partially responsible for these results.