Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ingestion or injection of the herbicide paraquat (1,1'-dimethyl-4,4'-dipyridylium dichloride) has caused more than 120 deaths in humans. Most have been due to respiratory failure caused by pulmonary edema, hemorrhage, and atelectasis, or subsequent pulmonary fibrosis. Paraquat is concentrated in lung tissue and is believed to cause superoxide radical formation in the presence of oxygen and suitable electron donors. Exposure to increased concentrations of oxygen has been reported to accelerate the toxicity of paraquat. The therapeutic efficacy of a reduced oxygen environment was investigated by exposing paraquat-poisoned mice to 10% oxygen after stepwise drops from 14% oxygen. Sixty-one mice were given intraperitoneal injections of 27 mg. per kg. of paraquat. The 25 mice in hypoxia for 7 days had a 32% mortality rate versus a 78% mortality rate for the remainder of the mice in room air, p less than 0.01. After a dose of 20 mg. per kg. of paraquat administered intraperitoneally, 24 mice in hypoxia had a 25% mortality rate versus 51% for 35 animals in room air. Brief exposures of the hypoxic group to "normoxia" (room air) led to pulmonary edema and death. The continuous exposure of paraquat-poisoned animals to hypoxic environments was protective. This approach may be useful in other oxidant lung injuries.
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PMID:Hypoxic protection in paraquat poisoning. 99 61

Superoxide anion (O2-) acts as an exacerbation factor in interstitial pneumonia. Lecithinized-superoxide dismutase (PC-SOD), which is synthesized with a lecithin derivative bound covalently to recombinant human Cu,Zn-SOD, has a longer half-life in plasma and higher affinity to cell membranes than unmodified SOD. The effect of PC-SOD was evaluated using the bleomycin-induced interstitial pneumonia mouse model. Treatment with PC-SOD at 10 mg/kg significantly reduced the hydroxyproline content and fibrosis score. Namely, PC-SOD suppressed the progression of pulmonary fibrosis on the bleomycin-induced interstitial pneumonia mouse model. PC-SOD may be a potential drug for interstitial pneumonia therapy.
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PMID:Effect of lecithinized-superoxide dismutase on the interstitial pneumonia model induced by bleomycin in mice. 933 91

Reactive oxygen species (ROS) have been implicated in the pathogenesis of fibrosis. However, it remains unclear which ROS is the major cause. We hypothesize that superoxide elicits specific toxicity to human lung fibroblasts and plays an important role in the development of pulmonary fibrosis. In this study, superoxide generated from xanthine and xanthine oxidase activated lung fibroblasts by increasing the release of TGF-beta1 and collagen. This was associated with increased levels of intracellular superoxide. SOD and tempol, by scavenging respectively extracellular and intracellular superoxide, prevented the activation of fibroblasts induced by exposure to exogenous superoxide, whereas catalase did not. Moreover, hydrogen peroxide did not activate fibroblasts. Apparently, superoxide rather than hydrogen peroxide is involved in the regulation of TGF-beta1 and collagen release in lung fibroblasts. The chloride channel blocker, DIDS, inhibited the increase of intracellular superoxide levels induced by exogenous superoxide and consequently prevented the activation of fibroblasts. This suggests that the cellular influx of superoxide through chloride channels is essential for superoxide-induced activation of fibroblasts. ERK1/2 and p38 MAPKs are involved in the intracellular pathway leading to superoxide-induced fibroblasts activation. Superoxide possesses until now undiscovered specific pro-fibrotic properties in human lung fibroblasts. This takes place via the cellular influx of superoxide through chloride channels rather than via the formation of hydrogen peroxide.
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PMID:Superoxide radicals increase transforming growth factor-beta1 and collagen release from human lung fibroblasts via cellular influx through chloride channels. 1926 87