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

The effectiveness of lung radiotherapy is limited by radiation tolerance of normal tissues and by the intrinsic radiosensitivity of lung cancer cells. The chemopreventive agent curcumin has known antioxidant and tumor cell radiosensitizing properties. Its usefulness in preventing radiation-induced pneumonopathy has not been tested previously. We evaluated dietary curcumin in radiation-induced pneumonopathy and lung tumor regression in a murine model. Mice were given 1% or 5% (w/w) dietary curcumin or control diet prior to irradiation and for the duration of the experiment. Lungs were evaluated at 3 weeks after irradiation for acute lung injury and inflammation by evaluating bronchoalveolar lavage (BAL) fluid content for proteins, neutrophils and at 4 months for pulmonary fibrosis. In a separate series of experiments, an orthotopic model of lung cancer using intravenously injected Lewis lung carcinoma (LLC) cells was used to exclude possible tumor radioprotection by dietary curcumin. In vitro, curcumin boosted antioxidant defenses by increasing heme oxygenase 1 (HO-1) levels in primary lung endothelial and fibroblast cells and blocked radiation-induced generation of reactive oxygen species (ROS). Dietary curcumin significantly increased HO-1 in lungs as early as after 1 week of feeding, coinciding with a steady-state level of curcumin in plasma. Although both 1% and 5% w/w dietary curcumin exerted physiological changes in lung tissues by significantly decreasing LPS-induced TNF-alpha production in lungs, only 5% dietary curcumin significantly improved survival of mice after irradiation and decreased radiation-induced lung fibrosis. Importantly, dietary curcumin did not protect LLC pulmonary metastases from radiation killing. Thus dietary curcumin ameliorates radiation-induced pulmonary fibrosis and increases mouse survival while not impairing tumor cell killing by radiation.
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PMID:Dietary curcumin increases antioxidant defenses in lung, ameliorates radiation-induced pulmonary fibrosis, and improves survival in mice. 2042 58

The authors investigated the role of leukotrienes (LTs) in the pathogenesis of silica-induced pulmonary fibrosis in mice during the progression from acute to chronic phases. Intratracheal instillation of silica particles induced progressive pulmonary fibrosis. The tissue content of cysteinyl (Cys) LTs and LTB(4) was markedly increased in the acute phase after silica instillation, concurrently with the up-regulation of LTB(4) receptor, transforming growth factor (TGF)-beta1, and tumor necrosis factor (TNF)-alpha, along with down-regulation of the CysLT type 2 receptor. Importantly, the tissue content of CysLTs and mRNA levels of TGF-beta1 and TNF-alpha were increased in the fibrotic lung in the chronic phase. Furthermore, strong immunohistochemical staining for the CysLT type 1 receptor, TNF-alpha, and TGF-beta1, but not for the CysLT type 2 receptor, was codetected in the pathological lesions during both acute and chronic phases. These findings suggest that an increase in LT production in the lung and modulation of homeostatic balance among LT receptors may contribute to the progression of pulmonary fibrosis.
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PMID:Involvement of leukotrienes in the pathogenesis of silica-induced pulmonary fibrosis in mice. 2049 24

Phosphoinositide 3-kinase-gamma (PI3Kgamma) has been identified to play the critical roles in inflammatory cells activation and recruitment in multiply inflammatory diseases and it promised to be a prospective target for relevant inflammatory diseases therapy. AS605240, a selective PI3Kgamma inhibitor, has been proved effective on several inflammatory diseases. In this study, we investigated the protective effect of AS605240 on bleomycin-induced pulmonary fibrosis in rats. Our results showed that orally administration of AS605240 significantly prevented lung inflammation and reduced collagen deposition. AS605240 also inhibited augmented expression of TNF-alpha and IL-1beta induced by bleomycin instillation. Moreover, the mRNA levels of TNF-alpha and IL-1beta in lung were remarkably suppressed. Histological assessment found that AS605240 reduced the expression of TGF-beta(1) and prevented T lymphocytes infiltration to lung. Phospho-Akt level in inflammatory cells by blocking PI3Kgamma was down-regulated and the inhibition of Akt phosphorylation was further confirmed by Western blot. Our findings illustrated that AS605240 was effective for preventing pulmonary fibrosis by suppressing inflammatory cells recruitment and production of inflammatory cytokines. These findings also suggest that PI3Kgamma may be a useful target in treating inflammation diseases and AS605240 may represent a promising novel agent for the future therapy of pulmonary fibrosis.
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PMID:A phosphoinositide 3-kinase-gamma inhibitor, AS605240 prevents bleomycin-induced pulmonary fibrosis in rats. 2051 Jun 75

It is widely accepted that inflammatory cells and cytokines play vital roles in the process of pulmonary fibrosis. The aim of this study was to evaluate the preventative effects of liposomal quercetin against bleomycin-induced pulmonary fibrosis in vivo. The underlying molecular mechanisms were also investigated. Bleomycin was injected intratracheally at a single dose of 5 U/kg for pulmonary fibrosis induction. Liposomal quercetin was intravenously injected 1 day prior to bleomycin administration and continued to the end of the study (for 4 weeks). Our results showed that liposomal quercetin diminished the increase of total cell counts and macrophage counts in bronchoalveolar lavage fluid. The neutrophil and lymphocyte counts were also significantly decreased both on day 7 and 14 after liposomal quercetin injection (P<0.05). The levels of TNF-alpha, IL-1beta, and IL-6 in bronchoalveolar lavage fluid at day 7 were strikingly reduced in liposomal quercetin treated group compared with bleomycin-induced group (TNF-alpha: 56.21+/-3.16 pg/ml vs.79.85+/-6.91 pg/ml; IL-1beta: 37.64+/-2.10 pg/ml vs. 73.29+/-5.78 pg/ml; IL-6: 88.52+/-5.96 pg/ml vs. 128.56+/-8.72 pg/ml; P<0.05). Moreover, the treatment with liposomal quercetin exerted approximately 35.8% reduction of the hydroxyproline content in contrast to the bleomycin-induced group (P<0.05). Histopathological assessment revealed that treatment with liposomal quercetin apparently lessened the lung fibrosis areas and collagen deposition accompanied with decreased expression of TGF-beta1. Thus, our results suggested that liposomal quercetin could attenuate the bleomycin-induced pulmonary fibrosis in vivo by the suppression of inflammatory cytokines.
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PMID:A further investigation concerning correlation between anti-fibrotic effect of liposomal quercetin and inflammatory cytokines in pulmonary fibrosis. 2051 Jun 84

Human health in the past and presently is influenced by the amounts and proportion of chemical elements to which humans have been exposed. Arsenic, as a therapeutic agent was known to ancient Greeks and Romans. Ehrlick introduced organic arsenicals as anti linetic agents but with advent of penicillin these have nearly become obsolete. Once considered toxic, harmful to humans, arsenic is now considered an essential ultra trace element at least in animals. Now the impact of arsenic on health is more from industrial and environmental than medicinal exposure. This article reviews human exposure to arsenic in non occupational population, mostly through drinking water which is a worldwide problem, more so in south East Asia. Sources of arsenic, normal and abnormal levels in blood and tissues levels, old and new methods of estimation of arsenic, mechanism of action of arsenic in experimental animal is briefly reviewed. Old described clinical manifestation of arsenic in humans is briefly reviewed and newly described clinical manifestations in human with special emphasis on atherosclerosis, liver and diabetes are discussed. Proposed biological mechanisms in experimental animals included up regulation of inflammatory signals like cytokines and TNF-alpha, oxidative stress, hypomethylation, decreased DNA repair and apoptosis, cell proliferation, angiogenesis, activation of several enzymes like methyl transferase which converts inorganic arsenic to MMA and DMA, and GSH in in-vivo and in-vitro in experimental rat liver slices. Experimentally NAC (N-Acetyl Cysteine) treatment attenuates oxidative stress in atherosclerosis apoptosis and liver injury. GSH probably plays an important role in deactivation of the intermediate products of arsenic metabolism and prevents peroxidation of membrane lipids. Chronic human exposure has been linked to several systems in the human body: dermal (exfoliative dermatitis, keratosis, vitiligo, skin cancer), peripheral neuropathy, encephalopathy, bronchitis, pulmonary fibrosis, hepatosplenomegaly resembling NCPF, portal hypertension, peripheral vascular disease and BFD, arteriosclerosis and cancers of lung, urinary bladder, other internal organs and diabetes. Experimental and epidemiological evidence support diabetes effect of high level arsenic exposure. Low and moderate exposure to arsenic in drinking water is widely prevalent and may play a role in diabetes prevalence and needs to be studied further. Role of arsenic in Indian arteriosclerosis, diabetes and liver diseases, (cirrhosis, NCPF), need to be studied further. Study of mechanisms and enzymes mentioned need to be studied in humans exposed to arsenic and other xenobiotics. Measuring arsenic exposure, metabolic and biologic effects by newly described and simpler urine proteomics may accelerate our understanding of arsenic on health consequences.
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PMID:Arsenicosis: review of recent advances. 2175 19

Curcumin (diferuloylmethane) is a yellow pigment present in the spice turmeric (Curcuma longa). It has been used for centuries in Ayurveda (Indian traditional medicine) for the treatment of several diseases. Over the last several decades, the therapeutic properties of curcumin have slowly been elucidated. It has been shown that curcumin has pleiotropic effects, regulating transcription factors (e.g., NF-kB), cytokines (e.g., IL6, TNF-alpha), adhesion molecules (e.g., ICAM-1), and enzymes (e.g., MMPs) that play a major role in inflammation and cancerogenesis. These effects may be relevant for several pulmonary diseases that are characterized by abnormal inflammatory responses, such as asthma or chronic obstructive pulmonary disease, acute respiratory distress syndrome, pulmonary fibrosis, and acute lung injury. Furthermore, some preliminary evidence suggests that curcumin may have a role in the treatment of lung cancer. The evidence for the use of curcumin in pulmonary disease is still sparse and has mostly been obtained using either in vitro or animal models. The most important issue with the use of curcumin in humans is its poor bioavailability, which makes it necessary to use adjuvants or curcumin nanoparticles or liposomes. The aim of this review is to summarize the available evidence on curcumin's effectiveness in pulmonary diseases, including lung cancer, and to provide our perspective on future research with curcumin so as to improve its pharmacological effects, as well as provide additional evidence of curcumin's efficacy in the treatment of pulmonary diseases.
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PMID:Curcumin use in pulmonary diseases: State of the art and future perspectives. 2788 57


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