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Paraquat-induced neutrophil alveolitis: Reduction of the inflammatory response by pretreatment with endotoxin and hyperoxia

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Abstract

Paraquat toxicity often presents as acute lung injury that progresses into the irreversible form of the adult respiratory distress syndrome (ARDS). To assess the role of inflammatory cells in paraquat toxicity and its modulation by endotoxin/hyperoxia pretreatment, rats were injected with paraquat (35 mg/kg i.p.) and injury monitored by histologic study and bronchoalveolar lavage. Forty-eight hours after paraquat administration, acute lung injury was confirmed by histologic study and was associated with an increase in lavage LDH activity from 0.37 ± 0.12 U/mg protein to 0.83 ± 0.22 U/mg protein (P < 0.05). Lavage revealed a decrease in alveolar macrophages, 95.6 ± 0.6 to 20.6 ± 3.4%, and an increase in neutrophils from 1.6 ± 0.2 to 70.6 ± 6.1% (P < 0.001 in both comparisons). Pretreatment of rats with endotoxin and hyperoxia prior to paraquat administration prolonged survival (P < 0.005), elevated endogenous superoxide dismutase and catalase levels in the lung (P < 0.005, both comparisons), and significantly reduced the inflammatory cell changes (P < 0.001). The protective role of this pretreatment regimen in paraquat toxicity may reflect a complex modulating effect on several parameters critical to the pathogenesis of paraquat-induced lung injury.

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  1. Mayo Clinic and Mayo Foundation, 200 First Street Southwest, 55905, Rochester, MN, USA

    W. J. Martin & D. M. Howard

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  1. W. J. Martin
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  2. D. M. Howard
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Martin, W.J., Howard, D.M. Paraquat-induced neutrophil alveolitis: Reduction of the inflammatory response by pretreatment with endotoxin and hyperoxia. Lung 164, 107–120 (1986). https://doi.org/10.1007/BF02713633

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