Degree Name
PhD (Doctor of Philosophy)
Program
Biomedical Sciences
Date of Award
May 1987
Abstract
Paraquat was administered to male, Sprague-Dawley rats via continous infusion, at dosage rates of 250 (LoPQ) or 500 (HiPQ) nmoles/hr for seven days. The purpose was to characterize the effects of prolonged, low blood levels of the herbicide on selected lung biochemical parameters. The efficacy of putrescine as an inhibitor of pulmonary paraquat accumulation, in vivo, was assessed in these animals by I.V. coinfusion of 2500 or 5000 nmoles putrescine/hr. Dose-dependent levels of both paraquat and putrescine were achieved by 18 hours and were maintained throughout the exposure period. Terminal lung paraquat content was also dose-dependent and up to 18-fold greater than corresponding blood levels, indicative of pulmonary accumulation of the herbicide. Despite relatively high putrescine dosage rates, resulting blood levels of this diamine were low and did not significantly alter terminal lung paraquat content. No evidence of paraquat toxicity was seen in LoPQ animals while frank toxicity was observed in the HiPQ animals beginning between the fourth and fifth day. Qualitative histopathological examination of the lungs revealed changes typical of paraquat toxicity (e.g., interstitial edema, increase in type II cells) resulting from HiPQ. Significant increases were found in levels of lung glutathione and activities of the GSH peroxidase system enzymes, glucose-6-phosphate dehydrogenase and GSSG reductase. These changes were probably the result of paraquat-induced oxidant stress and increased NADPH requirements. Elevations in lung putrescine, spermidine, and ornithine decarboxylase activity were detected in HiPQ animals only, and reflected the observed lung damage and/or resulting "proliferative" state of the tissue rather than a direct response to paraquat. As in the case of pulmonary oxygen toxicity, the increased levels of lung polyamines may serve to mediate a reparative response to paraquat-induced lung damage. The results demonstrate only a narrow difference between a paraquat dose which produces no apparent lung damage but stimulates components of the GSH peroxidase antioxidant system and one which causes characteristic, paraquat-induced lung damage. The experimental model employed here represents a useful means to study subtle, paraquat-induced biochemical and morphological alterations in lung by avoiding paraquat doses which rapidly produce lung damage or are directly toxic to extrapulmonary tissues.
Document Type
Dissertation - unrestricted
Recommended Citation
Dunbar, Jacob R., "Lung Paraquat Content and Effects on the Lung Glutathione Antioxidant System, Nadph, and Polyamines Resulting From Intravenous Coinfusion of Paraquat and Putrescine to Rats" (1987). Electronic Theses and Dissertations. Paper 2669. https://dc.etsu.edu/etd/2669