A biochemical study of pulmonary fibrosis

Iqbal, M., 1984. A biochemical study of pulmonary fibrosis. PhD, Nottingham Trent University.

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The development of pulmonary fibrosis in the rat has been investigated following both the intratracheal and intrabronchial instillation of bleomycin. These studies showed that the intratracheal and intrabronchial instillation of m equivalent dose of bleomycin resulted in changes in the lung which were different when measured by both histological and biochemical techniques. Following the intrabronchial instillation of O.5U of bleomycin (in 0.3ml saline), into the left lung, this lung showed extensive collagen deposition with eventual consolidation between 6 and I4 days. Comparison of the different models indicated that in each case the degree of fibrosis was dependent on both the dose of bleomycin and on the volume of saline in which it is instilled. In both models only those lung lobes which demonstrated histological evidence of extensive collagen deposition showed an increase in collagen concentration ( hydroxyproline/mg lung dry weight). Biochemical and histological studies suggested that uninjured areas of the lung underwent compensatory lung growth following bleomycin instillation.

Studies undertaken to investigate the effect of hyperoxia (70% oxygen) on the development of bleomycin-induced pulmonary fibrosis showed that the fibrotic response could be enhanced. This enhancement was only observed when animals were exposed to oxygen immediately after the intrabronchial instillation of bleomycin.

Investigations into the biochemical mechanism of bleomycin toxicity indicated that its toxicity to lung cells differed from that of the herbicide paraquat. Bleomycin failed to stimulate both the pentose phosphate pathway and the oxidant defence enzymes. Furthermore, pre-exposure of rats to 85% oxygen failed to reduce bleomycin induced toxicity.

An assessment of different biochemical parameters that may be used as markers of bleomycin induced pulmonary fibrosis indicated that levels of lung transglutaminase activity and putrescine accumulation into lung slices may be of potential use in this context.

Item Type: Thesis
Creators: Iqbal, M.
Date: 1984
ISBN: 9781369325652
Divisions: Schools > School of Science and Technology
Record created by: Laura Ward
Date Added: 06 Jul 2021 10:25
Last Modified: 10 Apr 2024 15:31
URI: https://irep.ntu.ac.uk/id/eprint/43343

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