RESUMO
Polyhexamethyleneguanidine phosphate (PHMG-P) is a biocide of guanidine family that can cause a fatal lung damage if exposed directly to the lungs. No reports exist regarding the toxicity of PHMG-P in neonatal animals. Therefore, this study aimed to determine PHMG-P toxicity in neonatal and 8-week-old mice after they were intranasally instilled with 1.5 mg/kg, 3 mg/kg, and 4.5 mg/kg PHMG-P. PHMG-P lung exposure resulted in more severe pulmonary toxicity in adult mice than in newborn mice. In the high-dose group of newborn mice, a minimal degree of inflammatory cell infiltration and fibrosis in the lung were detected, whereas more severe pathological lesions including granulomatous inflammation, fibrosis, and degeneration of the bronchiolar epithelium were observed in adult mice. At day 4, C-C motif chemokine ligand 2 (CCL2), a potent chemokine for monocytes, was upregulated but recovered to normal levels at day 15 in newborn mice. However, increased CCL2 and IL-6 levels were sustained at day 15 in adult mice. When comparing the differentially expressed genes of newborn and adult mice through RNA-seq analysis, there were expression changes in several genes associated with inflammation in neonates that were similar or different from those in adults. Although no significant lung damage occurred in newborns, growth inhibition was observed which was not reversed until the end of the experiment. Further research is needed to determine how growth inhibition from neonatal exposure to PHMG-P affects adolescent and young adult health.
Assuntos
Animais Recém-Nascidos , Quimiocina CCL2 , Guanidinas , Pulmão , Animais , Camundongos , Guanidinas/toxicidade , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Interleucina-6/metabolismo , Interleucina-6/genética , Camundongos Endogâmicos C57BL , Feminino , Masculino , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/patologiaRESUMO
Despite its widespread use as a stabilizer across various industries over the past several decades, the health effects of chronic exposure to PFOA are still unclear. We administered PFOA by oral gavage (0, 12.5, 50, and 200 µg/day/mouse, eight groups) to male and female mice for six months. Body weight gain decreased with dose accompanied by increased liver weight, and PFOA altered liver damage-related-blood biochemical indicators and induced pathological lesions, including hepatocellular hypertrophy, cholangiofibrosis, and centrilobular hepatocellular vacuolation. Loss of the Golgi apparatus, formation of lamellar body-like structures, and lipid accumulation were observed in the liver of PFOA-treated mice. We also cohabited five pairs of male and female mice for the last ten days of administration, dosed PFOA to dam up to 28 days after birth, and investigated effects on reproduction and development. The survival rate of pups and the sex ratio of surviving mice decreased significantly at the highest dose. PFOA tissue concentration increased with the dose in the parent mice's liver and the pups' blood and brain. Taken together, we suggest that PFOA primarily affects the liver and reproduction system and that disturbance in lipid metabolism and Golgi's structural stability may be involved in PFOA-induced toxicity.
Assuntos
Caprilatos , Fluorocarbonos , Complexo de Golgi , Fígado , Reprodução , Animais , Fluorocarbonos/toxicidade , Feminino , Masculino , Caprilatos/toxicidade , Camundongos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Complexo de Golgi/efeitos dos fármacos , Complexo de Golgi/metabolismo , Reprodução/efeitos dos fármacos , Administração Oral , Tamanho do Órgão/efeitos dos fármacos , Relação Dose-Resposta a DrogaRESUMO
Cigarette smoke induces an inflammatory response in the lungs by recruiting inflammatory cells, leading to lung diseases such as lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. Existing inhalation exposure methods for assessing the adverse effects of cigarette smoke require expensive equipment and are labor-intensive. Therefore, we attempted to develop a novel method to assess these adverse effects using intratracheal instillation (ITI) of whole cigarette smoke condensate (WCSC). The WCSC (0, 5, 10, or 20 mg/mL) was administered by ITI once daily for 6 or 12 days using an automatic video instillator. Repeated WCSC ITI increased the lung weight, and monocyte chemoattractant protein-1 (MCP-1), neutrophil, and lymphocyte levels within bronchoalveolar lavage fluid compared to the control. In the histopathological analysis of the lung tissue, a mild inflammatory response was observed in the 6 and 12 days 20 mg/mL WCSC exposure groups. The genome-wide RNA-seq expression patterns revealed that inflammatory and immune response-related genes, such as the chemokine signaling pathway, Th1/Th2 cell differentiation, and cytokine-cytokine receptor interaction, were employed following WCSC exposure. In addition, MCP-1 was time-dependent and increased in the 10 mg/mL exposure group compared to the control group. These results suggested that the WCSC might induce the potential pulmonary inflammatory response. Furthermore, we proposed that ITI may be a rapid and effective method of evaluating the adverse effects of WCSC within a short exposure period (less than 2 weeks), and it can be used to evaluate cigarette inhalation toxicity studies as an alternative method.
Assuntos
Fumar Cigarros , Pneumopatias , Doença Pulmonar Obstrutiva Crônica , Ratos , Animais , Pulmão , Doença Pulmonar Obstrutiva Crônica/metabolismo , Pneumopatias/patologia , Líquido da Lavagem BroncoalveolarRESUMO
Polyhexamethylene guanidine phosphate (PHMG-P), a cationic biocide, is widely used in household products due to its strong bactericidal activity and low toxicity. However, it causes fatal lung damage when inhaled. In this study, we investigated why PHMG-P causes fatal lung injury when inhaled, and demonstrated that the disruption of membrane integrity through ionic interaction-a molecular initiating event of PHMG-P-determines toxicity. Mice were injected intravenously with 0.9 or 7.2 mg/kg PHMG-P (IV group), or instilled intratracheally with 0.9 mg/kg PHMG-P (ITI group); they were euthanatized at 4 h and on days 1 and 7 after treatment. Increased total BAL cell count and proinflammatory cytokine production, along with fibrotic changes in the lungs, were detected in the ITI group only. Levels of hepatic enzymes and hepatic serum amyloid A mRNA expression were markedly upregulated in the 7.2 mg/kg IV and ITI groups at 4 h or day 1 after treatment, but returned to baseline. No pathological findings were detected in the heart, liver, or kidneys. To simulate the IV injection, A549, THP-1, and HepG2 cells were treated with PHMG-P in cell culture media supplemented with different serum concentrations. Increased serum concentration was associated with an increase in cell viability. These results support the idea that direct contact between PHMG-P and cell membranes is necessary for PHMG-induced toxicity.
Assuntos
Desinfetantes , Lesão Pulmonar , Animais , Desinfetantes/toxicidade , Guanidinas/toxicidade , Pulmão/patologia , Lesão Pulmonar/patologia , CamundongosRESUMO
Cigarette smoke (CS) is the leading cause of chronic pulmonary diseases, including lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. In this study, we aimed to investigate the effects of repeated CS exposure on polyhexamethylene guanidine (PHMG)-induced pulmonary fibrosis in mice. A single intratracheal instillation of 0.6 mg/kg PHMG enhanced the immune response of mice by increasing the number of total and specific inflammatory cell types in the bronchoalveolar lavage fluid. It induced histopathological changes such as granulomatous inflammation/fibrosis and macrophage infiltration in the lungs. These responses were upregulated upon exposure to a combination of PHMG and CS. In contrast, a 4-hr/day exposure to 300 mg/m3 CS alone for 2 weeks by nose-only inhalation resulted in minimal inflammation in the mouse lung. Furthermore, PHMG administration increased the expression of fibrogenic mediators, especially in the pulmonary tissues of the PHMG + CS group compared with that in the PHMG alone group. However, there was no upregulation in the expression of inflammatory cytokines following exposure to a combination of PHMG and CS. Our results demonstrate that repeated exposure to CS may promote the development of PHMG-induced pulmonary fibrosis.
Assuntos
Fibrose Pulmonar , Animais , Líquido da Lavagem Broncoalveolar , Guanidina , Guanidinas/toxicidade , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Fumaça/efeitos adversos , FumarRESUMO
BACKGROUND: Telemetry is a wireless implanted device that measures biological signals in conscious animals and usually requires surgery for its removal when the study is finished. After removing the device, the animals are either used for other studies or euthanatized. CASE PRESENTATION: Herein, we report the case of a living cynomolgus monkey (Macaca fascicularis) that was used for the entire experimental period, instead of euthanasia, after surgical removal of an implanted telemetry system. Radiography was used to determine the status of the implanted telemetry, following which, a repair surgery was performed for removing the system; clinical signs were used to preserve the life of the cynomolgus monkey. Postoperative clinical signs, food consumption, hematology, and serum biochemistry were examined during the 12-month observational period. No abnormal readings or conditions were observed in the subject after implant removal. CONCLUSIONS: This study may be a useful case report for living cynomolgus monkeys in telemetry implantations used throughout the study period. We suggest minimizing the suffering and improving the welfare of these animals.
RESUMO
This year, France banned the application of titanium dioxide nanoparticles as a food additive (hereafter, E171) based on the insufficient oral toxicity data. Here, we investigated the subchronic toxic responses of E171 (0, 10, 100, and 1,000 mg/kg) and tried to elucidate the possible toxic mechanism using AGS cells, a human stomach epithelial cell line. There were no dose-related changes in the Organisation for Economic Cooperation and Development test guideline-related endpoints. Meanwhile, E171 deeply penetrated cells lining the stomach tissues of rats, and the IgM and granulocyte-macrophage colony-stimulating factor levels were significantly lower in the blood from rats exposed to E171 compared with the control. The colonic antioxidant protein level decreased with increasing Ti accumulation. Additionally, after 24-h exposure, E171 located in the perinuclear region of AGS cells and affected expression of endoplasmic reticulum stress-related proteins. However, cell death was not observed up to the used maximum concentration. A gene profile analysis also showed that immune response-related microRNAs were most strongly affected by E171 exposure. Collectively, we concluded that the NOAEL of E171 for 90 days repeated oral administration is between 100 and 1,000 mg/kg for both male and female rats. Additionally, further study is needed to clarify the possible carcinogenesis following the chronic accumulation in the colon.
Assuntos
Aditivos Alimentares/toxicidade , Nanopartículas Metálicas/toxicidade , Titânio/toxicidade , Administração Oral , Animais , Feminino , França , Humanos , Masculino , Nível de Efeito Adverso não Observado , Tamanho da Partícula , RatosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Traditional herbal formula Gyejibokryeong-hwan (GJBRH; Guizhifuling-wan, Keishibukuryo-gan) consisting five medicinal herbs has been used to treat uterine disorders, gynecological diseases and blood stasis syndrome in Asia. AIM OF THE STUDY: We evaluated the safety of GJBRH in Crl:CD Sprague-Dawley (SD) rats over a period of 13 weeks. MATERIALS AND METHODS: To confirm the stability of the components of GJBRH, we analyzed the component contents in GJBRH at different storage periods, using high-performance liquid chromatography. Male and female SD rats were orally administered with GJBRH at doses of 0, 1000, 2000 and 5000â¯mg/kg/day for 13 weeks and assessed after a 4-week recovery period. Mortality, changes in body weight and food consumption, organ weights, hematology and serum biochemistry were monitored during the experimental period, along with clinical observations, ophthalmological examinations, urinalysis and histopathology. RESULTS: There were no significant differences among the eight marker compounds in GJBRH according to storage period. No significant GJBRH-treatment-related toxicological changes were observed in mortality or ophthalmological examinations in either sex. However, soft feces were observed in the male 5000â¯mg/kg/day group. In addition, there were significant changes in body weight and food consumption in both male and female rats treated with GJBRH at a dose of 5000â¯mg/kg/day. In the hematological examinations, we found a significant increase in white blood cells, neutrophils and fibrinogen in the 5000â¯mg/kg/day groups. In the urinalysis, a decrease in the total protein and albumin and an increase in the ovalbumin/globulin ratio were observed in both male and female rats treated with GJBRH at a dose of 5000â¯mg/kg/day. Histopathological examinations revealed erosion/ulcers and dilated glands in the stomachs of males from the 5000â¯mg/kg/day group, and squamous cell hyperplasia and epithelial atrophy was observed in the stomachs of both male and female rats treated with GJBRH at a dose of 5000â¯mg/kg/day. CONCLUSION: The no-observed-adverse-effect level (NOAEL) was 2000â¯mg/kg/day for both sexes.
Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Animais , Atrofia/induzido quimicamente , Contagem de Células Sanguíneas , Peso Corporal/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Medicamentos de Ervas Chinesas/análise , Ingestão de Alimentos/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Feminino , Hiperplasia/induzido quimicamente , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Nível de Efeito Adverso não Observado , Tamanho do Órgão/efeitos dos fármacos , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/toxicidade , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Baço/patologia , Estômago/efeitos dos fármacos , Estômago/patologia , Testes de Toxicidade SubcrônicaRESUMO
C57BL/6N mice are inbred strains widely used in biomedical research. Hence, a large amount of basic data has been accumulated. However, in the field of histopathology, spontaneous data for relatively younger mice that are used more frequently are not yet abundant, in contrast to data for older mice and their neoplastic lesions. To acquire the essential background data required by various research and toxicological assessments, 120 mice of the C57BL/6N strain (10 and 13 weeks of age) were collected from two institutions (From Korea and Japan) and subjected to histopathological analyses of the major organs (liver, spleen, kidney, thymus, heart, testis, epididymis). The results showed significantly higher incidence of sperm granulomas in the epididymides (10-56%) of these mice, compared with that in other strains or species of lab animals. Upon closer inspection, oligospermia/clear cell hyperplasia, cellular debris, and tubular vacuolation were also observed in the epididymides with sperm granulomas. Moreover, diseased organs were significantly heavier than healthy ones. Immunohistochemical staining showed a significant increase in the chromatic figures of cysteine-dependent aspartate-directed proteases-3 (caspase-3) and cleaved-poly(ADP-ribose) polymerase (c-PARP), and damages to the tubule due to spontaneous apoptosis, which may have led to the sperms leaking out of the tubule, causing the granuloma. To conclude, spontaneous sperm granuloma can occur in 10- and 13-week-old C57BL/6N mice and may thus affect the results of various studies using these mice. Therefore, sperm granuloma in epididymis needs to be carefully considered as an important factor when design the study using C57BL/6N.
RESUMO
Despite the excellent biocompatibility and antifouling effect of poly(ethylene glycol) (PEG), the high steric hindrance, limited chemical functionality, and low ligand multivalency of PEGylated nanocarriers often lead to inefficient cell targeting and intracellular trafficking. Hence, a new structure of hydrophilic corona allowing a higher ligand density without loss of excellent biocompatibility is highly desirable. Here we introduce tumor-targeted polyglycerolated (PGylated) nanocarriers that dramatically enhance the in vivo therapeutic efficacy of incorporated paclitaxel simply by increasing the surface density of hydrophobic tumor-targeting ligands. Linear polyglycerol-poly (ε-caprolactone) block copolymer (PG-b-PCL) is used to prepare PGylated lipiodol nanoemulsions, where PG serves as a corona conjugated with a large number of folic acid (FA) for efficient tumor targeting. Unlike FA-PEGylated nanoemulsions, FA-PGylated nanoemulsions can display a larger number of FA without structural destabilization. This property enables excellent anti-cancer activities and effective tumor regression in a cervical cancer xenograft murine model at a cumulative drug dose of â¼5 mg kg-1, which is about four fold smaller than that of commercial Taxol formulation. This study highlights the importance of surface chemistry of nanocarriers that enable multivalent ligand functionalization and high tolerance to the conjugation of hydrophobic ligands, which make PG as a very effective hydrophilic corona for in vivo drug delivery.
Assuntos
Portadores de Fármacos/química , Glicerol/química , Nanopartículas/química , Paclitaxel/uso terapêutico , Polímeros/química , Animais , Feminino , Fluorescência , Células HeLa , Humanos , Ligantes , Camundongos Endogâmicos BALB C , Camundongos Nus , Simulação de Dinâmica Molecular , Poliésteres/químicaAssuntos
Aorta , Coração/diagnóstico por imagem , Neoplasias do Timo/diagnóstico por imagem , Idoso , Humanos , Masculino , RadiografiaRESUMO
Amiodarone, bi-iodinated benzofuran derivative, is one of the most frequently prescribed and efficacious antiarrhythmic drugs. Despite its low incidence, amiodarone-induced pulmonary toxicity is of great concern and the leading cause of discontinuation. Autophagy is an essential homeostatic process that mediates continuous recycling of intracellular materials when nutrients are scarce. It either leads to a survival advantage or initiates death processes in cells under stress. In the present study, we investigated the role of autophagy in amiodarone-induced pulmonary toxicity. Amiodarone treatment-induced autophagy in H460 human lung epithelial cells and BEAS-2B normal human bronchial epithelial cells was demonstrated by increased LC3-II conversion, Atg7 upregulation, and autophagosome formation. Autophagic flux, as determined by the lysosomal inhibitor bafilomycin A1, was also increased following amiodarone treatment. To determine the role of autophagy in amiodarone toxicity, amiodarone-induced cell death was evaluated in the presence of 3-methyladenine or by knocking down the autophagy-related genes Atg7. Inhibition of autophagy decreased cellular viability and significantly increased apoptosis. Intratracheal instillation of amiodarone in rats increased the number of inflammatory cells recovered from bronchoalveolar lavage fluid, and periodic acid-Schiff-positive staining in bronchiolar epithelial cells. However, induction of autophagy by rapamycin treatment inhibited amiodarone-induced pulmonary toxicity. In conclusion, amiodarone treatment induced autophagy, which is involved in protection against cell death and pulmonary toxicity.
Assuntos
Amiodarona/toxicidade , Antiarrítmicos/toxicidade , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Adenina/análogos & derivados , Adenina/farmacologia , Administração por Inalação , Amiodarona/administração & dosagem , Animais , Antiarrítmicos/administração & dosagem , Proteína 7 Relacionada à Autofagia , Líquido da Lavagem Broncoalveolar/imunologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Técnicas de Silenciamento de Genes , Humanos , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Macrolídeos/farmacologia , Masculino , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , Ratos , Ratos Endogâmicos F344 , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Fatores de Tempo , Transfecção , Enzimas Ativadoras de Ubiquitina/metabolismoRESUMO
Triclosan (TCS) is a chemical compound used in household products as biocide. However, their pulmonary toxicity has been unclear. Thus, the purpose of this study was to investigate the possibility of injury to the lung by inhalation of TCS. Rats were exposed to TCS by single intratracheal instillation of 10 µg/B.W. kg for the low-dose group and 1,000 µg/B.W. kg for the high-dose group, respectively. TCS induced increase in the level of total cell (TC) count, polymorphonuclear leukocytes (PMNs), total protein (TP), lactate acid dehydrogenase (LDH), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) at 1 day after instillation. However, most pulmonary toxicity marker levels except TP in BALF were restored 14 days after instillation. In addition, TCS led to reduction of cell viability with morphological change in lung eptiehelial cells (L2 cell). Therefore, TCS may affect responses of acute inflammation and permeability in the lung.
Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Pulmão/efeitos dos fármacos , Traqueia , Triclosan/administração & dosagem , Triclosan/toxicidade , Lesão Pulmonar Aguda/patologia , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Produtos Domésticos , Instilação de Medicamentos , Pulmão/citologia , Pulmão/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Triclosan/metabolismoRESUMO
As chronic exposure to welding fumes causes pulmonary diseases, such as pneumoconiosis, public concern has increased regarding continued exposure to these hazardous gases in the workplace. In a previous study, the inflammatory response to welding fume exposure was analysed in rat lungs in the case of recurrent exposure and recovery periods. Thus using lung samples, well-annotated by histological observation and biochemical analysis, this study examines the gene expression profiles to identify phenotype-anchored genes corresponding to lung inflammation and the repair phenomenon after recurrent welding fume exposure. Seven genes (Mmp12, Cd5l, LOC50101, LOC69183, Spp1, and Slc26a4) were found to be significantly up-regulated according to the severity of the lung injury. In addition, the transcription and translation of Trem2, which was up-regulated in response to the repair process, were validated using a real-time polymerase chain reaction, Western blotting, and immunohistochemistry. The differentially expressed genes in the exposure and recovery groups were also classified using k-means and hierarchical clustering, plus their toxicological function and canonical pathways were further analysed using Ingenuity Pathways Analysis Software. As a result, this comprehensive and integrative analysis of the transcriptional changes that occur during repeated exposure provides important information on the inflammation and repair processes after welding-fume-induced lung injury.
Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Exposição por Inalação/análise , Lesão Pulmonar/induzido quimicamente , Transcriptoma , Soldagem , Análise de Variância , Animais , Western Blotting , Líquido da Lavagem Broncoalveolar/química , Análise por Conglomerados , Perfilação da Expressão Gênica , Imuno-Histoquímica , Pulmão/química , Pulmão/efeitos dos fármacos , Lesão Pulmonar/imunologia , Lesão Pulmonar/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Regulação para CimaRESUMO
Repeated exposure to welding fumes promotes a reversible increase in pulmonary disease risk, but the molecular mechanisms by which welding fumes induce lung injury and how the lung recovers from such insults are unclear. In the present study, pulmonary function and gene-expression profiles in the lung were analyzed by Affymetrix GeneChip microarray after 30 days of consecutive exposure to manual metal arc welding combined with stainless-steel (MMA-SS) welding fumes, and again after 30 days of recovery from MMA-SS fume exposure. In total, 577 genes were identified as being either up-regulated or down-regulated (over twofold changes, p < 0.05) in the lungs of low-dose or high-dose groups. Differentially expressed genes were classified based on a k-means clustering algorithm and biological functions and molecular networks were further analyzed using Ingenuity Pathways Analysis. Among the genes affected by exposure to or recovery from MMA-SS fumes, the transcriptional changes of 13 genes that were highly altered by treatment were confirmed by quantitative real-time PCR. Notably, Mmp12, Cd5l, Ccl7, Cxcl5, and Spp1 related to the immune response were up-regulated only in the exposure group, whereas Trem2, IgG-2a, Igh-1a, and Igh were persistently up-regulated in both the exposure and recovery groups. In addition, several genes that might play a role in the repair process of the lung were up-regulated exclusively in the recovery group. Collectively, these data may help elucidate the molecular mechanism of the recovery process of the lung after welding fume exposure.
Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Expressão Gênica/efeitos dos fármacos , Pulmão/patologia , Exposição Ocupacional/efeitos adversos , Aço Inoxidável , Soldagem , Animais , Líquido da Lavagem Broncoalveolar , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Pneumonia/genética , Pneumonia/patologia , RNA/biossíntese , RNA/genética , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The objectives of this study were to examine the lung injury and inflammation caused by manual metal arc stainless steel (MMA-SS) welding fume inhalation and to evaluate the recovery process. Sprague-Dawley rats were exposed to MMA-SS welding fumes for 2 h per day in a whole-body exposure chamber, with a total suspended particulate (TSP) concentration of 51.4 ± 2.8 mg/m3 (low dose) or 84.6 ± 2.9 mg/m3 (high dose) for 30 days. The animals were sacrificed after 30 days of exposure as well as after a 30-day recovery period. To assess the inflammatory or injury responses, cellular and biochemical parameters as well as cytokines were assayed in the bronchoalveolar lavage fluid (BALF). MMA-SS welding fume exposure led to a significant elevation in the number of alveolar macrophages (AM) and polymorphonuclear cells (PMN). Additionary, the values of ß-nacetyl glucosaminidase (ß-NAG) and lactate dehydrogenase (LDH) in the BALF were increased in the exposed group when compared to controls. After 30 days of recovery from exposure, a significant reduction in inflammatory parameters of BALF was observed between the exposed and recovered groups. Slight, but significant elevations were noted in the number of AM and PMN in the recovered groups, and AM that had been ingested fume particles still remain in the lungs. In conclusion, these results indicated that welding fumes induced inflammatory responses and cytotoxicity in the lungs of exposed rats. Fume particles were not fully cleared from lungs even after a 30-day recovery period.