Paraquat lung injury in rabbits

Abstract

An aerosol model for the study of paraquat (PQ) toxicity was developed using a 134 litre chamber and an ultrasonic nebuliser. Three groups of New Zealand white rabbits weighing 2-3 kg were studied. Group I (n=6) was exposed to 10 g PQ/100 ml double-distilled water (DDW), Group II (n=24) was exposed to 200 mg PQ/100 ml DDW and a control group (n=6) was exposed to 100 ml DDW. In a second experiment ten animals (Group III) were exposed to 10 mg PQ/100 ml DDW over a three-month period together with a control group (n=5). Group I animals died with extensive haemorrhagic pneumonitis 38 hours after the last challenge. Most animals in Group II surviving more than three exposures had a significant reduction (p<0.001) in arterial oxygen tension (PAO2) and an increase (p<0.001) in the alveolar-arterial O2 gradient. Specific compliance decreased (p<0.005) and functional residual capacity and breathing frequency increased (p<0.05). Tissue PQ values showed even pulmonary distribution, with evidence of PQ accumulation after repeated inhalation. The lungs showed focal interstitial fibrosis, interstitial thickening, proliferation of macrophages in the alveoli, epithelioid changes in the interstitium, Type II cell hyperplasia, and foci of acute inflammation with consolidation. Controls and Group III animals were normal. This indicates that repeated inhalation of paraquat aerosol induces dose-related interstitial pneumonitis and fibrosis in rabbits.