Humans ; Paraquat ; poisoning ; Pulmonary Fibrosis ; chemically induced ; pathology

Adult ; Antitubercular Agents ; adverse effects ; Humans ; Isoniazid ; adverse effects ; Male ; Pulmonary Fibrosis ; chemically induced ; diagnosis

OBJECTIVETo evaluate the effect of water channel aquaporin 4 (AQP4) on bleomycin-induced lung fibrosis in mice.

METHODSIn wild type and AQP4 gene knockout (AQP4-/-) mice, lung fibrosis was induced by injection of bleomycin (3 mg/kg) into the trachea and saline injection was used as a control. At d3, 7, 14, 28 after bleomycin-treatment, mice were randomly sacrificed in batch and the lung coefficient was determined. Serum levels of TGF-β1 and TNF-α were measured by ELISA and hydroxyproline contents in lung tissue were determined by Alkaline hydrolysis method. H-E staining and Masson's staining were performed to examine the pathological changes of lung tissues after bleomycin-treatment.

RESULTSOn d14 after bleomycin-treatment, the lung coefficients in wild type mice and AQP4-/- mice were 1.9-fold (12.69 ± 6.05 vs 6.80 ± 0.82, q=4.204, P<0.05) and 2.3-fold (14.05 ± 5.82 vs 6.05± 0.58, q=5.172, P<0.01) of that in control, respectively, but no significant difference was found between wild type and AQP4-/- mice in the lung coefficient value (P>0.05). The hydroxyproline contents in the lung increased after bleomycin-treatment; on d28, the lung hydroxyproline contents in wild type and in AQP4-/- mice were 1.55-fold (0.85 ± 0.22 g/mg vs 0.55 ± 0.14 μg/mg, q=4.313, P<0.05) and 1.4-fold (0.84 ± 0.13 μg/mg vs 0.60 ± 0.14μg/mg, q=4.595，P<0.05) of that in control, respectively, but no significant difference was noticed between wild type and AQP4-/- mice in lung hydroxyproline contents. There was a tendency that serum TGF-β1 and TNF-α levels increased in bleomycin-treated mice, but no significant difference was found between wild type and AQP4-/- mice. AQP4-knockout showed no effects on pathological changes of lung tissues with H-E staining and Masson's staining in mice with bleomycin-induced lung fibrosis.

CONCLUSIONAQP4 might not be involved in bleomycin-induced lung fibrosis in mice.

Animals ; Aquaporin 4 ; genetics ; Bleomycin ; toxicity ; Male ; Mice ; Mice, Knockout ; Pulmonary Fibrosis ; chemically induced ; genetics

BACKGROUNDBleomycin-induced fibrosis is extensively used to model aspects of the pathogenesis of interstitial pulmonary fibrosis. This study aimed to determine the benefic effects and mechanisms of simvastatin on bleomycin-induced pulmonary fibrosis in mice.

METHODSBleomycin-induced pulmonary fibrosis mice were administered with simvastatin in different doses for 28 days. We measured inflammatory response, fibrogenic cytokines and profibrogenic markers in both bleomycin-stimulated and control lungs, and correlated these parameters with pulmonary fibrosis.

RESULTSSimvastatin attenuated the histopathological change of bleomycin-induced pulmonary fibrosis and prevented the increase of lung hydroxyproline content and collagen (I and III) mRNA expression induced by bleomycin. Moreover, simvastatin down-regulated the increased expression of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) induced by bleomycin at both gene and protein levels. Simultaneously, the accumulation of neutrophils and lymphocytes and the increased production of tumor necrosis factor-alpha (TNF-alpha) in bronchial alveolar lavage fluid were inhibited by simvastatin in early inflammatory phase after bleomycin infusion. The higher dose of simvastatin was associated with a more significant reduction in these inflammatory and fibrotic parameters. Furthermore, the inactivation of p38, RhoA and Smad2/3 signaling pathways was observed during simvastatin administration.

CONCLUSIONSSimvastatin attenuated bleomycin-induced pulmonary fibrosis, as indicated by decreases in Ashcroft score and lung collagen accumulation. The inhibitory effect of simvastatin on the progression of pulmonary fibrosis may be demonstrated by reducing inflammatory response and production of TGF-beta1 and CTGF. These findings indicate that simvastatin may be used in the treatment of pulmonary fibrosis.

Animals ; Antibiotics, Antineoplastic ; Bleomycin ; Mice ; Mice, Inbred C57BL ; Pulmonary Fibrosis ; chemically induced ; metabolism ; pathology ; Simvastatin ; pharmacology

OBJECTIVETo observe the lung injury in rats induced by SiO₂ nanoparticles.

METHODSOne hundred and fifty SD rats were divided into five groups: the control group, the nanosized SiO₂ groups of 6.25, 12.5, 25 mg/ml, and the microsized SiO₂ group of 25 mg/ml, 30 rats each group. On the 7th, 15th, 30th, 60th and 90th day after exposure, six rats were sacrificed at each time point and the lung viscera coefficient, the pathological morphology and ultrastructure of lung were observed.

RESULTSAt each time point, the rat lung viscera coefficient of 25 mg/ml microsized SiO₂ and nanosized SiO₂ group were higher than the physiological saline group (P < 0.05), 25 mg/ml microsized SiO₂ group was higher than the same dose of nanosized SiO₂ group (P < 0.05); With longer duration of dye dust, lung viscera coefficient of 25 mg/ml microsized SiO₂ group and each dose of nanosized SiO₂ group were in time-effect relationship. Under light microscope we can see microsized SiO₂ group gradually formed cellularity nodules, and fused into fibrous nodules; At the early stage 25 mg/ml nanosized SiO₂ group occured focal alveolar macrophages and fibroblast proliferation and later fibrous connective tissue proliferated. Under TEM osmium lamellar corpuscle of type II alveolar epithelial cells were abnormal, and collagen and elastic fiber proliferated in mesenchyme of microsized and nanosized SiO₂ group.

CONCLUSIONNanosized SiO₂ particles after exposure can cause lung tissue injury in rat, and at the early stage it is showed inflammation, and later mainly characterized by pulmonary interstitial fibrosis differing from nodular lung fibrosis caused by microsized SiO₂, its ability to fibrosis is weaker compared with the same concentration of microsized SiO₂.

Animals ; Lung ; drug effects ; pathology ; ultrastructure ; Lung Injury ; chemically induced ; Male ; Nanoparticles ; toxicity ; Pulmonary Fibrosis ; chemically induced ; pathology ; Rats ; Rats, Sprague-Dawley ; Silicon Dioxide ; toxicity

OBJECTIVETo observe the effects of Fuzheng Huayu Recipe (FHR) on rat's renal interstitial fibrosis induced by mercuric chloride (HgCl2), and to explore preliminarily its mechanism of action.

METHODSRats were randomly divided into four groups: the normal group, the model group, the FHR group and the vitamin E group, the latter two were treated respectively by FHR 4.6 g/kg and vitamin E 100 mg/kg. Rats model was established by oral administration of 8 mg/kg HgCl2 for 9 weeks. Serum creatinine (Cr) and urea nitrogen (BUN) content were tested with corresponding test kits; hydroxyproline (Hyp) content in kidney was assayed with hydrochloric acid hydrolysis; renal histologic change was observed with HE, Masson and methenamine silver (PASM) staining; and collagen type I (Col I), as well as protein expressions of fibronectin (FN) and alpha-smooth muscle actin (alpha-SMA) was determined with Western blot.

RESULTSCompared with the model group, the kidney/body weight ratio, serum levels of Cr and BUN, kidney Hyp content, and severity of renal interstitial fibrosis in the two treated groups were significantly lower (P<0.05 or P<0.01), and the improvements were more significant in the FHR group than those in the vitamin E group; Col I and FN protein expression was also weaker in the two treated group (Col, P<0.05; FN, P<0.01); while the expression of alpha-SMA was lower in the FHR group (P<0.01), but it wasn't in the vitamin E group (P>0.05).

CONCLUSIONFHR could improve the HgCl2-induced renal function injury in rats, decrease extracellular matrix deposition and restrain renal interstitial fibrosis, the mechanism of action might be related with its inhibitory effect on myofibroblast activation.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Fibrosis ; chemically induced ; Kidney Diseases ; chemically induced ; drug therapy ; pathology ; Male ; Mercuric Chloride ; Phytotherapy ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the prevalence of betel nut chewing and oral submucous fibrosis (OSF) among elementary and middle school students in Loudi city, Hunan province.

METHODSAccording to the standard of the third national oral health epidemiological investigation, the subjects were selected through a two-stage random sampling procedure. A face to face questionnaire survey was conducted among students by random sampling from 6 schools, and oral examination was performed to find the prevalence of OSF.

RESULTSOf the 4087 eligible students, 4019 students participated in the survey(98.3%). Among the 4019 students, there were 498 betel nut chewers, the prevalence of betel nut chewing was 12.4%, which was much higher in male than in female students (437/2073, 21.1% vs 61/1946, 3.1%, P < 0.05). The proportion of students who were chewing areca nuts increased with increasing grades (P < 0.05). The prevalence was highest in senior schools (229/1077, 21.3%)and lowest in elementary schools (126/1983, 6.4%). Most students who were chewing areca nuts in elementary school obtained betel nuts from their parents (61/126, 48.4%), but most middle school betel nut chewers obtained betel nuts from their friends (88/143, 61.5% and 165/229, 72.1%). Five OSF cases (0.12%) were diagnosed among the 4019 students, all of them were male senior school students.

CONCLUSIONSBetel nut chewing was common and OSF cases were found among elementary and middle school students in Loudi city. There were more male than female students who were chewing betel nut.

Adolescent ; Areca ; Child ; China ; epidemiology ; Female ; Humans ; Male ; Mastication ; Oral Submucous Fibrosis ; chemically induced ; epidemiology ; Prevalence ; Students ; Surveys and Questionnaires

OBJECTIVETo study the pulmonary toxicity to rats induced by the nanosized SiO(2) or the standard SiO(2).

METHODSSeventy-two male SD rats were divided into three groups: the nanosized SiO(2) group, the standard SiO(2) group and the control group. 24 rats each group. The nanosized SiO(2) group and the standard SiO(2) group were instilled intratracheally with 0.5 ml suspension of 0.6 mg/ml nanosized SiO(2) or standard SiO(2) respectively while the control group was instilled with 0.5 ml physiological saline. On the 3rd, 7th, 14th, and 28th day after exposure, six rats were sacrificed at each time point and the total white cells counts and total protein in BALF and the histopathological changes were observed. The pulmonary toxicities of the two SiO(2) dusts were compared.

RESULTSNanosized SiO(2) caused significant increase at 3rd, 7th, 14th day after the exposure [(16.0 +/- 6.0) x 10(6), (11.1 +/- 4.0) x 10(6), (12.2 +/- 4.6) x 10(6)] compared with saline (P < 0.05 or P < 0.01) in the total numbers of white cells and on the 3rd after the exposure compared with standard SiO(2) [(5.7 +/- 3.7) x 10(6), P < 0.01]. Meanwhile, Nanosized SiO(2) significantly increased the total protein on the 14th, 28th day after the exposure (0.41 +/- 0.14, 0.41 +/- 0.19 g/L) compared with saline or standard SiO(2) and nanosized SiO(2) on the 3rd, 7th day after the exposure (P < 0.05 or P < 0.01). Nanosized SiO(2)-treated rats showed marked white cell infiltration in alveolar space or around brondum the blood vessel. Standard SiO(2) caused similar but less severe responses compared with nanosized SiO(2). Van Gieson's-stained sections showed no significant fibrosis in these dust-exposed rats at 28th day after the exposure.

CONCLUSIONNanosized SiO(2) can cause severer and longer pulmonary toxicity in rats than standard SiO(2). The pulmonary particle load threshold of nanosized SiO(2) may be lower than that of standard SiO(2).

Animals ; Male ; Nanoparticles ; toxicity ; Particle Size ; Pulmonary Fibrosis ; chemically induced ; Rats ; Rats, Sprague-Dawley ; Silicon Dioxide ; toxicity

Paraquat (PQ) is a highly effective herbicide with contact toxicity. PQ mainly accumulates in the lungs after absorption into the blood circulation. The respiratory function failure caused by PQ-induced lung injury, especially the irreversible pulmonary fibrosis in late phase, is the leading cause of death in patients with PQ poisoning. The mechanism of PQ poisoning is still unclear. Now it is speculated that oxidative stress and inflammation injury are the main pathogenic mechanisms, and abnormal gene expression, mitochondrial damage, loss of pulmonary surfactant, cytokine network and unbalanced matrix metalloproteinases/tissue inhibitors may be also involved in the pathogenesis. In addition to reducing poison absorption and increasing its removal, the current clinical treatment is mainly composed of antioxidant and anti-immune response, but has poor therapeutic effects. Although many novel methods of treatment have been proposed, most of them are still in the experimental stage. It is a hot spot to clarify the mechanism of PQ poisoning and to seek safe and effective treatment of pulmonary fibrosis. This article reviews the research progress on pathogenesis and treatment of PQ-induced pulmonary fibrosis.
Antioxidants ; Gene Expression ; Humans ; Inflammation ; Lung ; pathology ; Oxidative Stress ; Paraquat ; poisoning ; Pulmonary Fibrosis ; chemically induced ; pathology ; therapy

OBJECTIVETo report the clinical features and the prognosis, the methods of diagnosis and treatment, and the early detection of the pulmonary toxicity induced by amiodarone.

METHODThe clinical course, the findings of X-ray and CT and the results of treatment were summarized and analyzed in six patients with amiodarone-induced pulmonary toxicity.

RESULTSFive males, one female, aged 62 - 69 (66.0 +/- 2.4) years. Amiodarone was used because of paroxysmal atrial fibrillation in five patients and ventricular arrhythmia in one. The loading dose was 7 g and the maintaining dose was 0.2 g/d or less. Pulmonary toxicity was recognized at the times in 0.5 - 4.0 (2.1 +/- 1.3) years after amiodarone therapy. Dyspnea occurred, crack rales were audible in both lower parts of the lungs, and the chest X-ray showed grid-like changes in case one. No symptom was found in the others. Their diagnosis was made according to the pulmonary intestinal changes by high-resolution computerized tomography when the lung marking was increased or deranged by chest X-ray during the regular follow-up. Pulmonary function examination showed that the restrictive ventilation and the CO diffusing capacity decreased in case one, while the CO diffusing capacity was normal in the others. The decreased obstructive ventilation capacity was found in case six. Amiodarone was discontinued in all the cases after the diagnosis of induced pulmonary toxicity. One patient was treated with corticosteroid, three with azithromycin, and the another two patients were not treated with drug. During 0.1 - 5.0 year period of follow-up the symptoms were markedly attenuated in case one, and no new symptoms and radiography findings were found in the others.

CONCLUSIONSPulmonary toxicity is a serious adverse effect of amiodarone. The typical feature is pulmonary intestinal fibrosis and thick pulmonary intestine in the early stage. Corticosteroid treatment seems effective. It would be helpful for early diagnosis to take chest X-ray examination regularly and CT examination in suspicions cases during the therapy. The prognosis may be good in the early diagnosed cases.

Aged ; Amiodarone ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Pulmonary Fibrosis ; chemically induced ; diagnostic imaging ; Radiography