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)

The study was undertaken to investigate the influence of alpha-tocopherol (vitamin E) on malondialdehyde (MDA) and glutathione (GSH) levels and catalase (CAT) activity in lung of rats with bleomycin-induced pulmonary fibrosis (PF). Fourteen Wistar-albino rats were randomly divided into two groups of seven animals each. The first group was treated intra-tracheally with bleomycin hydrochloride (BM group); the second group was also instilled with BM but received injections of alpha-tocopherol twice a week (BM + E group). The third group was treated in the same manner with saline solution only, acting as controls (C). There were decreases in GSH level and CAT activity while an increase in MDA level in BM group was found compared to the control group (p < 0.05). Vitamin E had a regulator effect on these parameters. After administration of alpha-tocopherol, the increase in GSH level and CAT activity and the decrease in MDA level were seen in BM + E group compared to BM group (p < 0.05). Distinct histopathological changes were found in the BM group compared to the untreated rats. Less severe fibrotic lesions were also observed in the BM + E group. The results show that vitamin E is effective on the prevention of BM-induced PF, as indicated by differences in the lung levels of oxidants and antioxidants.
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PMID:Protective effect of alpha-tocopherol on oxidative stress in experimental pulmonary fibrosis in rats. 1698 Dec 17

Yin-Chiao-San (YCS), a kampo medicine, is widely used for patients with pulmonary disease and was applied for the treatment of SARS in Asia countries in 2003. For this reason, the present study investigated the preventive effect of YCS on bleomycin (BLM)-induced pulmonary fibrosis (PF) in rats. Animals were divided into four groups: (1) saline control group; (2) BLM-induced group, in which 15 mg/kg BLM was intraperitoneally injected three times per week for a period of 5 weeks; (3) BLM + vitamin E (10 mg/kg/day) as a positive group; (4) and BLM + YCS (1000 mg/kg/day). After 35 days, the rats were anesthetized, killed and then the lungs and bronchoalveolar lavage fluids (BALFs) were collected. The attenuation of pulmonary fibrosis was estimated according to the lung index, malondialdehyde (MDA), catalase (CAT), hydroxyproline (HP) and tumor necrosis factor-alpha (TNF-alpha) level in lung tissue and BALF. The serial sections of lung were stained with haematoxylin-eosin and Masson trichrome for histopathological observation of pulmonary fibrosis. The results indicated that YCS significantly reduced the lung index, MDA, HP and TNF-alpha, but YCS significantly enhanced the CAT level when compared with the BLM-induced group (p < 0.05). Additionally, the BLM group displayed severe histopathological change in the lung tissue, but YCS treatment could attenuate the BLM-induced PF. In conclusion, the results demonstrated that YCS possesses antioxidant and antiinflammatory activities and also inhibited collagen formation. Thus, YCS exhibited a preventive effect in BLM-induced PF and it is suggested that YCS may be applied to attenuate the side effects of BLM in chemotherapy.
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PMID:A kampo medicine, Yin-Chiao-san, prevents bleomycin-induced pulmonary injury in rats. 1717 25

The present study aimed to examine the antioxidant properties of Houttuynia cordata (HC) and its protective effect on bleomycin-induced pulmonary fibrosis in rats. Results showed that aqueous extract of HC exhibited a different magnitude of antioxidant activities in all model systems tested. Although HC showed weaker free radical scavenging and xanthine oxidase inhibitory activity than vitamin E, its anti-lipid peroxidation activity in rat liver homogenate was close to that of vitamin E. In animal studies, HC significantly decreased the levels of superoxide dismutase, malondialdehyde, hydroxyproline, interferon-gamma, and tumor necrosis factor-alpha. However, an increase in the concentration of catalase was noted in the bronchoalveolar lavage fluid. HC also remarkably improved the morphological appearance of the lung of bleomycin-treated rats. These results suggest that HC possesses a protective effect against bleomycin-induced pulmonary fibrosis. Interestingly, this protective effect was more pronounced than that of vitamin E. In conclusion, the protective effect of HC on pulmonary fibrosis could be partly associated with the reduction of oxidative damage caused by bleomycin.
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PMID:Protective effect of Houttuynia cordata extract on bleomycin-induced pulmonary fibrosis in rats. 1759 5

Diallylsulfide (DAS), an antioxidant and anti-inflammatory agent was evaluated for its ability to repress lung fibrosis induced by bleomycin in Wistar rats. A single intra tracheal administration of bleomycin (6.5 U/kg BW) was administered to pulmonary fibrosis group, while DAS (120 mg/kg BW) was administered intraperitoneally throughout the experimental period. Fibrotic changes in the lungs were estimated by measuring lung hydroxyproline content. Bleomycin administration significantly (P<0.05) reduced the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the lung tissues. Bleomycin caused a significant decrease in the level of reduced glutathione (GSH), which was accompanied with significant increase in lipid peroxidation (LPO) level, and myeloperoxidase (MPO) activity, in the lung tissues. An increase in the level of cell counts in bronchoalveolar lavage fluid (BALF) was observed in bleomycin induced group. DAS administration altered the levels of enzymic antioxidants, TBARS, MPO and GSH towards normal values. Histopathological analysis and picrosirius red staining showed an increased collagen deposition in rats receiving bleomycin alone that was decreased upon DAS treatment. Immunohistochemical studies revealed that DAS reduced the bleomycin-induced activation of inducible nitric oxide synthase (iNOS) and nuclear factor kappa-B (NF-kappaB) and decreased the augmented levels of the early inflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), in the lung tissues. The present study provides evidence that DAS might serve as a novel target for the therapeutic treatment of lung fibrosis.
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PMID:Diallyl sulfide attenuates bleomycin-induced pulmonary fibrosis: critical role of iNOS, NF-kappaB, TNF-alpha and IL-1beta. 1846 59

Oxidative stress resulting from an imbalance between radical-generating and radical scavenging systems plays an important role in the pathogenesis of pulmonary fibrosis. Epigallocatechin-3-gallate (EGCG), a polyphenol and a major component of green tea, possess a potent antioxidant property. This study was designed to evaluate the potential antioxidative activity of EGCG in the plasma and lungs during bleomycin induced experimental pulmonary fibrosis. Intratracheal administration of bleomycin (6.5 U/kg body weight) to rats resulted in significant reduction of body weight, enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) and non-enzymic antioxidants (reduced glutathione, vitamin C, vitamin E and vitamin A). Elevations in lung W/D (wet weight/dry weight) ratio, hydroxyproline content was observed with a synchronized increase in lipid peroxidation markers (thiobarbituric acid reactive substances and hydroperoxides). Intraperitoneal administration of EGCG at a dose of 20 mg/kg body weight significantly improved the body weight, enzymic and non enzymic antioxidants and considerably decreased the W/D ratio, hydroxyproline and lipid peroxidation marker levels. Histological observations also correlated with the biochemical parameters. Thus, this study confirms the beneficial use of EGCG in alleviating the oxidative stress induced during pulmonary fibrosis.
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PMID:Enhancement of antioxidant defense system by epigallocatechin-3-gallate during bleomycin induced experimental pulmonary fibrosis. 1859 65

Cigarette smoke toxicants are well known for their debilitating effects on lungs. Cigarette smoke toxicities cause various respiratory disorders including pulmonary emphysema, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis and cancer. Farnesol, an isoprenoid, is known to possess anti-inflammatory and chemopreventive properties. In this study we report the protective efficacy of farnesol against massive lung inflammation, oxidative stress and consequent injuries caused by cigarette smoke toxicants. Farnesol was administered by gavage (50 and 100 mg/kg b.wt. in corn oil) one time daily for 7 days. On day 7 lung injuries were induced by intratracheal instillation of aqueous cigarette smoke extract (CSE). LDH, total cell count, total protein, phospholipid content and MDA formation were measured in bronchoalveolar lavage fluid (BALF). In lung tissue H2O2 content, reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx) and catalase activities were evaluated. Prophylactic treatment with farnesol significantly shows lung protection by lowering the levels of LDH, total cell count, total protein and MDA in BALF. Farnesol maintained the phospholipid content of BALF in a positive manner. In lung tissue it positively modulated the CSE altered activities of GR, GPx and catalase. There was a marked increase in GSH content and decrease in H2O2 content of lung tissue by farnesol administration. Histopathological findings correlate with cellular and biochemical parameters of the lungs and potentiate the protective role of farnesol against CSE induced lung inflammation and injuries. These results suggest a potent role of farnesol in protection of lung against cigarette smoke toxicants induced lung injuries.
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PMID:Farnesol ameliorates massive inflammation, oxidative stress and lung injury induced by intratracheal instillation of cigarette smoke extract in rats: an initial step in lung chemoprevention. 1879 22

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

Abnormal repair and dysregulated angiogenesis have been implicated in the pathogenesis of pulmonary fibrosis, but the underlying mechanisms of regulation are not well understood. The present study investigated the role of phosphatidylinositol-3-kinase (PI3K)/Akt in fibrogenesis of human lung fibroblasts and its regulation by reactive oxygen species (ROS). Exposure of lung fibroblasts to bleomycin, a known inducer of fibrosis, resulted in rapid activation of PI3K/Akt and a parallel increase in fibroblast proliferation and collagen production, characteristics of lung fibrosis. Bleomycin had no significant effect on total Akt protein expression but induced phosphorylation of the protein at threonine 308 and serine 473 positions. Inhibition of this phosphorylation by PI3K inhibitors or by dominant-negative Akt (T308A/S473A) expression abrogated the effects of bleomycin on fibroblast proliferation and collagen production, suggesting the role of PI3K/Akt in the fibrogenic process. Activation of PI3K/Akt by bleomycin also led to transcriptional activation and protein expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor, which contributed to the fibroproliferative and collagen-inducing effects of bleomycin. The fibrogenic effects of bleomycin were dependent on ROS generation, particularly superoxide anion and hydrogen peroxide, which were induced by bleomycin. Inhibition of ROS generation by antioxidant enzymes, catalase and superoxide dismutase mimetic MnTBAP, abrogated the fibrogenic effects of bleomycin as well as its induction of PI3K/Akt and HIF-1alpha activation. Together, our results indicate a novel role of PI3K/Akt in fibrogenesis of human lung fibroblasts and its regulation by ROS, which could be exploited for the treatment of pulmonary fibrosis and related disorders.
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PMID:Phosphatidylinositol-3-kinase/akt regulates bleomycin-induced fibroblast proliferation and collagen production. 1952 Sep 17

The release of reactive oxygen species (ROS) and cytokines by alveolar macrophages has been demonstrated in asbestos-induced pulmonary fibrosis, but the mechanism linking alveolar macrophages to the pathogenesis is not known. The GTPase Rac1 is a second messenger that plays an important role in host defense. In this study, we demonstrate that Rac1 null mice are protected from asbestos-induced pulmonary fibrosis, as determined by histological and biochemical analysis. We hypothesized that Rac1 induced pulmonary fibrosis via generation of ROS. Asbestos increased TNF-alpha and ROS in a Rac1-dependent manner. TNF-alpha was elevated only 1 day after exposure, whereas ROS generation progressively increased in bronchoalveolar lavage cells obtained from wild-type (WT) mice. To determine whether ROS generation contributed to pulmonary fibrosis, we overexpressed catalase in WT monocytes and observed a decrease in ROS generation in vitro. More importantly, administration of catalase to WT mice attenuated the development of fibrosis in vivo. For the first time, these results demonstrate that Rac1 plays a crucial role in asbestos-induced pulmonary fibrosis. Moreover, it suggests that a simple intervention may be useful to prevent progression of the disease.
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PMID:Modulation of reactive oxygen species by Rac1 or catalase prevents asbestos-induced pulmonary fibrosis. 1968 99

Idiopathic pulmonary fibrosis (IPF) is thought to involve inflammatory infiltration of leukocytes, lung injury induced by reactive oxygen species (ROS), in particular superoxide anion, and fibrosis (collagen deposition). No treatment has been shown to improve definitively the prognosis for IPF patients. Superoxide dismutase (SOD) catalyzes the dismutation of superoxide anion to hydrogen peroxide, which is subsequently detoxified by catalase. Lecithinized SOD (PC-SOD) has overcome clinical limitations of SOD, including low tissue affinity and low stability in plasma. In this study, we examined the effect of PC-SOD on bleomycin-induced pulmonary fibrosis. Severity of the bleomycin-induced fibrosis in mice was assessed by various methods, including determination of hydroxyproline levels in lung tissue. Intravenous administration of PC-SOD suppressed the bleomycin-induced increase in the number of leukocytes in bronchoalveolar lavage fluid. Bleomycin-induced collagen deposition and increased hydroxyproline levels in the lung were also suppressed in animals treated with PC-SOD, suggesting that PC-SOD suppresses bleomycin-induced pulmonary fibrosis. The dose-response profile of PC-SOD was bell-shaped, but concurrent administration of catalase restored the ameliorative effect at high doses of PC-SOD. Intratracheal administration or inhalation of PC-SOD also attenuated the bleomycin-induced inflammatory response and fibrosis. The bell-shaped dose-response profile of PC-SOD was not observed for these routes of administration. We consider that, compared with intravenous administration, inhalation of PC-SOD may be a more therapeutically beneficial route of administration due to the higher safety and quality of life of the patient treated with this drug.
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PMID:Therapeutic effect of lecithinized superoxide dismutase on bleomycin-induced pulmonary fibrosis. 2003 62


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