A Novel Lung Slice System with Compromised Antioxidant Defenses

Abstract

In order to facilitate the study ofoxidative stress in lung tissue, rat lung slices with impaired antioxidant defenses were prepared and used. Incubation of lung slices with the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea(BCNU) (100 M) Inanaminoacid-rich mediumfor 45 minproduced a near-maximal (approximately 85 %), irreversible inhibition of glutathione reductase, accompanied by only a modest (approximately 15 %) decrease in pulmonary nonprotein sulfhydryls (NPSH) and no alteration in intracellular ATP, NADPI, and NADPH levels. The amounts of NADP(H), ATP, and NPSH were stable over a 4-hr incubation period following the removal from BCNU. The viability of the system was further evaluated by measuring the rate of evolution of "4CO2 from D-[4C(UJ)-glucose. The rates ofevolution were almost identical in the compromised system when compared with control slices over a 4-hr time period. By using slices with compromised oxidative defenses, preliminary results have been obtained with paraquat, nitrofurantoin, and 2,3-dimethoxy-1,4-naphthoquinone.