Interestingly, this TFP-mediated rise of intracellular ROS occurred much faster in bleomycin-treated cells than in cisplatin-treated cells, which is in agreement with the faster kinetics of apoptosis induction by bleomycin compared with cisplatin.
This could be achieved by bleomycin, a cytostatic agent with the ability to form a complex with DNA and RNA.
We observed that the pulmonary fibrotic response elicited by bleomycin in mice challenged with P. aeruginosa prior to bleomycin instillation was markedly diminished compared with the uninfected control group.
In one study, mice with fibrosis induced by bleomycin had diminished damage and collagen deposition in the lung due to the migration of MSC [ 16].
Recent studies have shown that alveolar macrophages (AM) can be stimulated by bleomycin in vitro releasing inflammatory cytokines, suggesting that the interaction of bleomycin with AM is an important step in the drug-induced fibrotic process.
Flavonoids can also protect the DNA by directly interacting with the mutagen agents, as in the induced chromosomal aberration by bleomycin alluded by Heo et al. [ 35].
However, we unexpectedly discovered fibrosis in both lungs with signs of bronchiolitis obliterans and focally organizing pneumonia, probably induced by bleomycin, while liver lesions were absent.
In this chapter the spectrum of lung toxicities of the more traditional chemotherapeutic agents are discussed with some focus on redox-directed chemotherapeutics and their related lung toxicities, as best exemplified by bleomycin.
However, in this model, MMP-7 levels were measured and found to not be induced by bleomycin instillation.
In a mouse model of lung injury induced by bleomycin, bleomycin-induced epithelial damage was mediated through TG2, resulting in IL-6 release and the differentiation of IL-17-producing T cells, with subsequent inflammatory amplification in the lung [ 56].
