RESUMO
This systematic review aimed to summarize the available data on the treatment of pulmonary contusions with exogenous surfactants, determine whether this treatment benefits patients with severe pulmonary contusions, and evaluate the optimal type of surfactant, method of administration, and drug concentration. Three databases (MEDline, Scopus, and Web of Science) were searched using the following keywords: pulmonary surfactant, surface-active agents, exogenous surfactant, pulmonary contusion, and lung contusion for articles published between 1945 and February 2023, with no language restrictions. Four reviewers independently rated the studies for inclusion, and the other four reviewers resolved conflicts. Of the 100 articles screened, six articles were included in the review. Owing to the limited number of papers on this topic, various types of studies were included (two clinical studies, two experiments, and two case reports). In all the studies, surfactant administration improved the selected ventilation parameters. The most frequently used type of surfactant was Curosurf® in the concentration of 25 mg/kg of ideal body weight. In most studies, the administration of a surfactant by bronchoscopy into the segmental bronchi was the preferable way of administration. In both clinical studies, patients who received surfactants required shorter ventilation times. The administration of exogenous surfactants improved ventilatory parameters and, thus, reduced the need for less aggressive artificial lung ventilation and ventilation days. The animal-derived surfactant Curosurf® seems to be the most suitable substance; however, the ideal concentration remains unclear. The ideal route of administration involves a bronchoscope in the segmental bronchi.
Assuntos
Contusões , Lesão Pulmonar , Surfactantes Pulmonares , Síndrome do Desconforto Respiratório , Humanos , Surfactantes Pulmonares/administração & dosagem , Surfactantes Pulmonares/uso terapêutico , Contusões/tratamento farmacológico , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/etiologia , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/etiologia , Animais , Respiração Artificial/métodos , Resultado do Tratamento , Broncoscopia/métodosRESUMO
PURPOSE: This study aimed to investigate the role of 17ß-estradiol (E2) in the repair of contusion-induced myoinjury in mice and to identify the underlying molecular mechanisms. METHODS: In vivo, contusion protocol was performed for preparing mice myoinjury model, and Injection (i.p.) of 17ß-estradiol (E2) or estrogen receptor antagonist ICI 182,780, or ovariectomy (OVX), was used to alter estrogen level of animal models. In vitro, C2C12 myoblasts were treated with H2O2 (oxidative stress inducer), SIRT1 inhibitor EX527, or aromatase inhibitor anastrozole. Serum E2 level was assessed by enzyme-linked immunosorbent assay (ELISA). Muscle damage repair was evaluated by H&E staining and the activities of serum creatine kinase (CK) and lactate dehydrogenase (LDH). The oxidative stress was estimated by the levels of catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA). Western blot was performed to measure the protein expressions of SIRT1, PGC-1α, Nrf2, and HO-1. RESULTS: We observed the elevated serum E2 levels and the upregulated oxidative stress in damaged muscle in female mice after contusion-induction. The E2 administration in vivo alleviated contusion-induced myoinjury in OVX mice by reducing CK and LDH activities, suppressing oxidative stress, and enhancing the expression levels of SIRT1, PGC-1α, Nrf2, and HO-1. These effects were inhibited by treatment with an ERα/ß antagonist. Moreover, EX527 or anastrozole treatment exacerbated H2O2-induced growth inhibition and oxidative stress, and expression downregulation of SIRT1, PGC-1α, Nrf2, and HO-1 in C2C12 cells in vitro. CONCLUSION: Our results suggest that E2 is a positive intervention factor for muscle repair followed contusion-induced myoinjury, through its effects on suppressing oxidative stress via activating the SIRT1/PGC-1α/Nrf2 pathway.
Assuntos
Contusões , Estradiol , Músculo Esquelético , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Sirtuína 1 , Animais , Feminino , Camundongos , Anastrozol/farmacologia , Anastrozol/uso terapêutico , Contusões/tratamento farmacológico , Modelos Animais de Doenças , Estradiol/farmacologia , Estradiol/uso terapêutico , Peróxido de Hidrogênio/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/lesões , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Sirtuína 1/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismoRESUMO
BACKGROUND: Acute cardiac contusion induced by trauma is known with its high mortality and morbidity. The role of oxidative stress and inflammation in its pathophysiology has led to the investigation of antioxidant and anti-inflammatory substances in non-sur-gical treatment. In this study, the effects of rutin which has these two features on acute cardiac contusion were investigated. METHODS: Thirty male albino Wistar rats were divided into three equal groups as healthy (HG), contusion (CG), and rutin + con-tusion (rutin + CG). A heart contusion was created dropping 200 g weight from 1-m height onto anterior thorax of CG (n=10) and Rutin + CG (n=10) group animals by anesthetizing with intraperitoneal administration of 60 mg/kg ketamine and xylazine inhalation at appropriate intervals. Thirty minutes after contusion was applied, rutin at the dose of 50 mg/kg was administered orally to the stomach by gavage to the rutin + CG group animals. The rutin was used once a day for 2 days. Rats were killed at the end of 48 h. Heart tissues were removed and examined biochemically and histopathologically. Troponin I (TP I) and creatine kinase-MB (CK-MB) were measured in blood samples taken from the tail veins just before the rats were killed. RESULTS: TP I, CK-MB, malondialdehyde, total oxidant status, and nuclear factor-kappa B levels increased in the CG when compared to the HG, and Rutin application prevented this increase, total glutathione (eGSH) and total antioxidant status levels decreased, and rutin application prevented this decrease. Histopathological findings also supported these findings. CONCLUSION: Rutin had a protective effect on heart tissue.
Assuntos
Contusões , Contusões Miocárdicas , Animais , Antioxidantes/farmacologia , Contusões/tratamento farmacológico , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Rutina/farmacologia , Rutina/uso terapêuticoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: As a folk medicine, Aconitum sinomontanum Nakai (Ranunculaceae) a perennial herbaceous flowering plant, is a widely used traditional Chinese medicine. Its rhizomes and roots are known as 'Gaowutou' in China, and it has been traditionally used for the treatment of rheumatoid arthritis, painful swelling of joints, bruises and injuries and has been known to grow well in regions of high altitude such as Gansu, Tibet etc. THE AIM OF THE REVIEW: This systematic review the comprehensive knowledge of the A. sinomontanum, including its traditional processing and uses, chemical constituents, pharmacological activities, toxicity assessment, pharmacokinetics and metabolism, and its use in clinical settings to emphasize the benefits of this species. We also discuss expectations for prospective research and implementation of this herb. This work lays a solid foundation for further development of A. sinomontanum. MATERIALS AND METHOD: Information on the studies of A. sinomontanum was collected from scientific journals, books, and reports via library and electronic data search (PubMed, Elsevier, Scopus, Google Scholar, Springer, Science Direct, Wiley, ACS, EMBASE, Web of Science and CNKI). Meanwhile, it was also obtained from published works of material medica, folk records, ethnopharmacological literatures, Ph.D. and Masters dissertation. RESULTS: As a member of the Ranunculaceae family, A. sinomontanum possesses its up-and-coming biological characteristics. It is widely reported for treating rheumatoid arthritis, painful swelling of joints, bruises and injuries. Currently, over 71 phytochemical ingredients have been obtained and identified from different parts of A. sinomontanum. Among them, alkaloids, flavonoids, steroids, glycosides are the major bioactive constituents. Activities such as antinociceptive, anti-inflammatory, antitumor, antiarrhythmic, local anesthetic, antipyretic, antimicrobial, insecticidal and others have been corroborated in vivo and in vitro. These properties are attributed to different alkaloids. In addition, many of the active ingredients, such as lappaconitine, ranaconitine and total alkaloids have been used as quality markers. CONCLUSION: This work contributes to update the ethnopharmacological uses, chemical constituents, pharmacological activities, toxicity assessment, pharmacokinetics and metabolism, and clinical settings information for A. sinomontanum, which provide basic information to help better understand the pharmacological and toxicological activities of A. sinomontanum in human. However, further in-depth studies are needed to determine the medical uses of this herb and its chemical constituents, pharmacological activities, clinical applications and toxicology.
Assuntos
Aconitum , Alcaloides , Artrite Reumatoide , Contusões , Ranunculaceae , Aconitum/química , Artrite Reumatoide/tratamento farmacológico , Contusões/tratamento farmacológico , Etnofarmacologia , Humanos , Medicina Tradicional Chinesa , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Estudos ProspectivosRESUMO
<b>Background and Objective:</b> Contusion in skeletal muscles were common in athletes.<sup> </sup>Contusions usually occur when the tissue is exposed to a rapid and strong compressive force, for example, a direct blow, which usually results in the formation of a hematoma within the muscle. Contusion injuries impair the physiological function of the muscle. Supplementation is needed to shorten the healing process. Alternative therapy is antioxidant supplementation. Therefore, we conducted a study on the administration of the antioxidant selenium in contusion rats. <b>Materials and Methods:</b> The subject of this study were male Wistar rats. Rats were divided into 3 groups, namely control group, contusion group and selenium group. Each group consisted of 5 rats. Selenium dose was 0.0513 mg kg<sup>1</sup> b.wt., dissolved into 2% PGA given once a day, for 3 consecutive days. After treatment periods, CK-MM level, IL-1ß and IL-6 level were examined. <b>Results:</b> Protein expression of IL-1ß and IL-6 were significantly lower in the selenium treatment group compared to the contusion group. These results were confirmed by improved step gait in the selenium group. But there was no significant decrease in serum CK-MM levels expression in the selenium treatment group when compared to the contusion group. <b>Conclusion:</b> Selenium supplementation improved gait function after contusion by suppressing IL-1ß and IL-6 expression. However, selenium administration did not alter CK-MM levels.
Assuntos
Contusões , Selênio , Animais , Contusões/tratamento farmacológico , Suplementos Nutricionais , Interleucina-6 , Masculino , Ratos , Ratos Wistar , Selênio/farmacologiaRESUMO
BACKGROUND: This study investigated the molecular mediators of prolonged hematopoietic progenitor cell mobilization a trauma and chronic stress and the role of propranolol in modifying this response. METHODS: Sprague-Dawley rats were randomized to lung contusion (LC), LC plus hemorrhagic shock (LCHS), or LCHS with daily restraint stress (LCHS/CS). Propranolol was administered daily. Bone marrow (BM) and lung expression of high mobility group box 1 (HMGB1), granulocyte colony-stimulating factor (G-CSF), neutrophil elastase, stromal cell-derived factor 1 (SDF-1)/CXR4, and vascular cell adhesion protein 1 (VCAM-1)/very late antigen-4 were measured by real-time polymerase chain reaction. RESULTS: Bone marrow HMGB1, G-CSF, and neutrophil elastase expression were significantly elevated two- to four-fold after LCHS/CS, and all were decreased with the use of propranolol. SDF-1 and VCAM-1 were both significantly decreased after LCHS/CS. CONCLUSIONS: The increased expression of HMGB1 and G-CSF and decreased expression of BM anchoring molecules, SDF-1 and VCAM-1, after LCHS/CS, likely mediates prolonged hematopoietic progenitor cell mobilization. Propranolol's ability to reduce HMGB1, G-CSF, and neutrophil elastase expression suggests that the mobilization of hematopoietic progenitor cells was driven by persistent hypercatecholaminemia.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Contusões/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Lesão Pulmonar/metabolismo , Propranolol/farmacologia , Choque Hemorrágico/metabolismo , Estresse Fisiológico/fisiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Animais , Biomarcadores/metabolismo , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Doença Crônica , Contusões/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Células-Tronco Hematopoéticas/efeitos dos fármacos , Lesão Pulmonar/tratamento farmacológico , Masculino , Propranolol/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Restrição Física , Choque Hemorrágico/tratamento farmacológicoRESUMO
INTRODUCTION: Propranolol has been shown to improve erythroid progenitor cell growth and anemia following trauma and this study sought to investigate the mechanisms involved by evaluating the effects of selective beta blockade. METHODS: Male Sprague-Dawley rats were subjected to lung contusion, hemorrhagic shock and chronic stress (LCHS/CS) ± daily selective beta-1, beta-2, or beta-3 blockade (B1B, B2B, B3B). Bone marrow cellularity and growth of erythroid progenitor colonies, hemoglobin, plasma granulocyte colony-stimulating factor (G-CSF), hematopoietic progenitor cell mobilization, and daily weight were assessed. RESULTS: Selective beta-2 and beta-3 blockade improved bone marrow cellularity, erythroid progenitor colony growth and hemoglobin levels, while decreasing plasma G-CSF, progenitor cell mobilization and weight loss following LCHS/CS. CONCLUSIONS: Attenuating the neuroendocrine stress response with the use of selective beta-2 and 3 adrenergic blockade may be an alternative to improve bone marrow erythroid function following trauma.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Medula Óssea/efeitos dos fármacos , Contusões/tratamento farmacológico , Lesão Pulmonar/tratamento farmacológico , Propranolol/farmacologia , Choque Hemorrágico/tratamento farmacológico , Estresse Fisiológico/efeitos dos fármacos , Antagonistas Adrenérgicos beta/uso terapêutico , Animais , Biomarcadores/metabolismo , Medula Óssea/metabolismo , Medula Óssea/patologia , Medula Óssea/fisiopatologia , Contusões/fisiopatologia , Lesão Pulmonar/fisiopatologia , Masculino , Propranolol/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Choque Hemorrágico/fisiopatologiaRESUMO
INTRODUCTION: Bosentan is an endothelin-1 receptor antagonist with anti-inflammatory, antioxidant, and antiproliferative effects. We aimed to evaluate its effects on lung tissue in a pulmonary contusion (PC) model. MATERIALS AND METHODS: The rats were randomly divided into five groups: PC3: PC evaluated on the 3rd day (n = 8), PC-B3: PC enteral bosentan 100 mg/kg/day, for 3 days (n = 8), PC7: PC evaluated on the 7th day (n = 7), PC-B7: PC 7 days bosentan 100 mg/kg/day, for 7 days (n = 8), C: control (n = 6). Unilateral lung contusion was created by dropping a metal weight onto the chest. The rats were sacrificed on the 3rd or the 7th days. The lung tissue was evaluated histopathologically for alveolar edema, congestion, and leukocyte infiltration, biochemically for malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) levels, and immunohistochemically for inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and apoptosis scores. RESULTS: Alveolar edema, congestion, and leukocyte infiltration scores were increased in all groups compared with the control group (p < 0.05) and decreased in bosentan-treated groups compared with the relevant nontreated groups (p < 0.05). Fibrosis was observed only in PC7 and PC-B7 groups. Bosentan did not have any effect on fibrosis development. iNOS and eNOS levels were higher in all groups compared with the control (p < 0.05) without a difference in the nontreated versus treated groups (p > 0.05). Bosentan treatment caused decreased MDA and increased SOD levels in comparison to the nontreated groups (p < 0.05). Tissue NO levels did not show any significant difference among groups. PC groups had higher levels of apoptosis compared with the control group (p < 0.05). The degree of apoptosis decreased in bosentan-treated groups compared with the nontreated groups (p < 0.05). CONCLUSION: PC causes progressive lung tissue damage. Bosentan reduced leukocyte infiltration and alveolar edema and congestion caused by PC. It also decreased MDA levels and increased SOD levels. Bosentan prevents tissue damage by inhibiting acute inflammatory response and reduces oxidative stress secondary to inflammation. It has therapeutic effects on apoptosis.
Assuntos
Bosentana/uso terapêutico , Contusões/tratamento farmacológico , Antagonistas dos Receptores de Endotelina/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Ferimentos não Penetrantes/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Contusões/metabolismo , Contusões/patologia , Endotelina-1/antagonistas & inibidores , Marcação In Situ das Extremidades Cortadas , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Ferimentos não Penetrantes/metabolismo , Ferimentos não Penetrantes/patologiaAssuntos
Anticoagulantes/uso terapêutico , Contusões/tratamento farmacológico , Lesão Pulmonar/tratamento farmacológico , Adulto , Feminino , Humanos , Incidência , Tempo de Internação/estatística & dados numéricos , Lesão Pulmonar/mortalidade , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo , Pneumonia/epidemiologia , Pontuação de Propensão , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Traqueotomia/estatística & dados numéricosRESUMO
Melittin is a major peptide component of sweet bee venom that possesses anti-allergic, anti-inflammatory, anti-arthritis, anti-cancer, and neuroprotective properties. However, the therapeutic effects of melittin on muscle injury have not been elucidated. We investigated the therapeutic effects of melittin on muscle injury in a mouse model of muscle contusion. The biceps femoris muscle of the mice was injured using drop mass method, and the animals were treated with melittin (4, 20, or 100 µg/kg) for 7 days. Melittin significantly increased: locomotor activity in open field test, and treadmill running activity in a dose-dependent manner to level comparable to the positive control, diclofenac (30 mg/kg). Melittin treatment attenuated the pro-inflammatory cytokine MCP-1, TNF-α and IL-6. The expression of muscle regeneration biomarkers, including MyoD (muscle differentiation marker), myogenin, smooth muscle actin, and myosin heavy chain was markedly increased in the injured muscle tissue of melittin-treated mice, as determined by western blotting and quantitative real-time polymerase chain reaction. These results demonstrate that melittin inhibits inflammatory response and improves muscle damage by regenerating muscles in a mouse model of muscle contusion. Taken together, the results of present study suggest that melittin is a promising candidate for the muscle injury treatment.
Assuntos
Anti-Inflamatórios , Venenos de Abelha/farmacologia , Contusões/metabolismo , Meliteno/farmacologia , Músculo Esquelético/metabolismo , Actinas/genética , Actinas/metabolismo , Animais , Venenos de Abelha/uso terapêutico , Quimiocina CCL2/metabolismo , Contusões/tratamento farmacológico , Contusões/genética , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Expressão Gênica , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Masculino , Meliteno/uso terapêutico , Camundongos Endogâmicos C57BL , Proteína MyoD/genética , Proteína MyoD/metabolismo , Miogenina/genética , Miogenina/metabolismo , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Regeneração/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Microglia are activated after spinal cord injury (SCI), but their phagocytic mechanisms and link to neuroprotection remain incompletely characterized. Docosahexaenoic acid (DHA) has been shown to have significant neuroprotective effects after hemisection and compression SCI and can directly affect microglia in these injury models. In rodent contusion SCI, we demonstrate that DHA (500 nmol/kg) administered acutely post-injury confers neuroprotection and enhances locomotor recovery, and also exerts a complex modulation of the microglial response to injury. In rodents, at 7 days after SCI, the level of phagocytosed myelin within Iba1-positive or P2Y12-positive cells was significantly lower after DHA treatment, and this occurred in parallel with an increase in intracellular miR-124 expression. Furthermore, intraspinal administration of a miR-124 inhibitor significantly reduced the DHA-induced decrease in myelin phagocytosis in mice at 7 days post-SCI. In rat spinal primary microglia cultures, DHA reduced the phagocytic response to myelin, which was associated with an increase in miR-124, but not miR-155. A similar response was observed in a microglia cell line (BV2) treated with DHA, and the effect was blocked by a miR-124 inhibitor. Furthermore, the phagocytic response of BV2 cells to stressed neurones was also reduced in the presence of DHA. In peripheral monocyte-derived macrophages, the expression of the M1, but not the M0 or M2 phenotype, was reduced by DHA, but the phagocytic activation was not altered. These findings show that DHA induces neuroprotection in contusion injury. Furthermore, the improved outcome is via a miR-124-dependent reduction in the phagocytic response of microglia.
Assuntos
Ácidos Docosa-Hexaenoicos/uso terapêutico , MicroRNAs/metabolismo , Microglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Contusões/tratamento farmacológico , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/farmacologia , Feminino , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microglia/citologia , Microglia/metabolismo , Bainha de Mielina/metabolismo , Neurônios/metabolismo , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Células PC12 , Ratos , Ratos Sprague-DawleyRESUMO
AIM: The activation of the TNFR2 receptor is beneficial in several pathologies of the central nervous system, and this study examines whether it can ameliorate the recovery process following spinal cord injury. METHODS: EHD2-sc-mTNFR2 , an agonist specific for TNFR2, was used to treat neurons exposed to high levels of glutamate in vitro. In vivo, it was infused directly to the spinal cord via osmotic pumps immediately after a contusion to the cord at the T9 level. Locomotion behavior was assessed for 6 weeks, and the tissue was analyzed (lesion size, RNA and protein expression, cell death) after injury. Somatosensory evoked potentials were also measured in response to hindlimb stimulation. RESULTS: The activation of TNFR2 protected neurons from glutamate-mediated excitotoxicity through the activation of phosphoinositide-3 kinase gamma in vitro and improved the locomotion of animals following spinal cord injury. The extent of the injury was not affected by infusing EHD2-sc-mTNFR2 , but higher levels of neurofilament H and 2', 3'-cyclic-nucleotide 3'-phosphodiesterase were observed 6 weeks after the injury. Finally, the activation of TNFR2 after injury increased the neural response recorded in the cortex following hindlimb stimulation. CONCLUSION: The activation of TNFR2 in the spinal cord following contusive injury leads to enhanced locomotion and better cortical responses to hindlimb stimulation.
Assuntos
Contusões/tratamento farmacológico , Receptores Tipo II do Fator de Necrose Tumoral/agonistas , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Células Cultivadas , Classe Ib de Fosfatidilinositol 3-Quinase/fisiologia , Citocinas/análise , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Receptores Tipo II do Fator de Necrose Tumoral/fisiologia , Medula Espinal/efeitos dos fármacos , Traumatismos da Medula Espinal/imunologiaRESUMO
BACKGROUND: Attenuating post-injury neuroendocrine stress abrogates persistent injury-associated anemia. Our objective was to examine the mechanisms by which propranolol and clonidine modulate this process. We hypothesized that propranolol and clonidine would decrease bone marrow expression of high-mobility group box-1 (HMGB1) and increase expression of stem cell factor (SCF) and B-cell lymphoma-extra large (Bcl-xL). METHODS: Male Sprague-Dawley rats were allocated to naïve control, lung contusion followed by hemorrhagic shock (LCHS), or LCHS plus daily chronic restraint stress (LCHS/CS) ±propranolol, ±clonidine. Day seven bone marrow expression of HMGB1, SCF, and Bcl-xL was assessed by polymerase chain reaction. RESULTS: Following LCHS, HMGB1 was decreased by propranolol (49% decrease, pâ¯=â¯0.012) and clonidine (54% decrease, pâ¯<â¯0.010). SCF was decreased following LCHS/CS, and was increased by propranolol (629% increase, pâ¯<â¯0.001) and clonidine (468% increase, pâ¯<â¯0.001). Bcl-xL was decreased following LCHS/CS, and was increased by propranolol (59% increase, pâ¯=â¯0.006) and clonidine (77% increase, pâ¯<â¯0.001). CONCLUSIONS: Following severe trauma, propranolol and clonidine abrogate persistent injury-associated anemia by modulating bone marrow cytokines, favoring effective erythropoiesis.
Assuntos
Medula Óssea/efeitos dos fármacos , Clonidina/farmacologia , Citocinas/metabolismo , Hematínicos/farmacologia , Lesão Pulmonar/fisiopatologia , Propranolol/farmacologia , Estresse Fisiológico/fisiologia , Anemia/etiologia , Anemia/prevenção & controle , Animais , Biomarcadores/metabolismo , Medula Óssea/metabolismo , Doença Crônica , Clonidina/uso terapêutico , Contusões/tratamento farmacológico , Contusões/fisiopatologia , Quimioterapia Combinada , Eritropoese/efeitos dos fármacos , Hematínicos/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Masculino , Propranolol/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Restrição Física , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/fisiopatologia , Resultado do TratamentoRESUMO
OBJECTIVE: Nowadays, there seems to be no decisive way for treatment of spinal cord injury (SCI).Extensive cell death (apoptosis and necrosis) occurring in SCI can cause considerable progressive sensorimotor disabilities. Preventing cell death by improving endogenous regenerative capability could an effective strategy for the treatment of SCI. This study was designed to evaluate the effects of lithium chloride (LiCl) on the cell survival through overexpression of BDNF and NT3 mRNA level and their receptors in the contusion rat models. METHODS: Rats were randomly divided into four experimental groups (eight rats/group) including: contused animals (the non-treatment group); contused animals (the control group) which received laminectomy; contused animals received normal saline (vehicle)and contused animals received intraperitoneal injection of 20 mg/kg LiCl three days after surgery. Injection continued for 14 days as treatment. Basso, Beattie, Bresnahan (BBB) rating scale was used to assess the motor function of the rats. To evaluate the histopathological and gene expression analysis, rats were sacrificed 28 days after surgery. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was performed to obtain the relative levels of mRNA for BDNF, NT3 and their receptors. RESULTS: The results showed LiCl ameliorates BBB scores via up-regulation of BDNF and TrkB receptors. Also, histological analysis showed that the numerical density per area of TUNEL- positive cells and the percentage of cavity significantly decreased in the LiCl-treated group. CONCLUSION: Our findings suggest that LiCl protects neural cells and effectively enhances locomotor function, which was done through up-regulation of endogenous BDNF expression in rats with SCI. ABBREVIATIONS: SCI: spinal cord injury; LiCl: lithium chloride; BDNF: Brain-derived neurotrophic factor; NT3: Neurotrophin-3; BBB: Basso, Beattie, Bresnahan; TrkB: Tropomyosin receptor kinase B; TUNEL: Terminal deoxynucleotidyl transferase dUTP nick end labeling.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Contusões/tratamento farmacológico , Cloreto de Lítio/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Atividade Motora/fisiologia , Fatores de Crescimento Neural/efeitos dos fármacos , Neurotrofina 3 , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia , Medula Espinal/patologia , Traumatismos da Medula Espinal/patologiaRESUMO
In recent decades, the number of people who practice sports has grown exponentially, increasing the number of muscular injuries. Trauma injury occurs when the muscle is exposed to a sudden compression force. Melatonin (MLT) has often been cited in the literature as a potent antioxidant and anti-inflammatory agent. This study was designed to evaluate MLT action on muscle tissue in Wistar rats in an experimental model of muscle trauma. Twenty-eight Wistar rats were used, divided into four groups: CO (Control), COâ¯+â¯MLT (Controlâ¯+â¯Melatonin), T (Trauma) and Tâ¯+â¯MLT (Traumaâ¯+â¯Melatonin). MLT (20â¯mg/kg) was administered (ip) daily at dusk until day 7. The trauma occurred on day 1, 2â¯h before the first MLT application. On day 8, muscle tissue was collected for histological analysis (HE), immunohistochemistry (TNF-α and NFκB), evaluation of oxidative stress through analysis of lipoperoxidation by TBARS and activity of SOD and GPx enzymes, and analysis of nitrites and nitrates. In the evaluation of TBARS and SOD, we observed a significant increase in the T group and a significant decrease in the Tâ¯+â¯MLT group. In the evaluation of GPx, there was a significant increase in the T group and a significant decrease in the Tâ¯+â¯MLT group. The histological analysis of muscle tissue revealed structural changes of muscle fibers and inflammatory infiltrate in the T group but a decrease in this damage in the Tâ¯+â¯MLT group. In the immunohistochemical evaluation, increased expression of TNFα and NFκB proteins in the T group was observed and a significant decrease of this expression in the Tâ¯+â¯MLT group. MLT was shown to attenuate oxidative damage and to diminish the expression of inflammatory proteins and tissue damage in this experimental model.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Contusões/tratamento farmacológico , Melatonina/uso terapêutico , Músculo Quadríceps/lesões , Ferimentos não Penetrantes/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Contusões/patologia , Avaliação Pré-Clínica de Medicamentos , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Melatonina/farmacologia , Fibras Musculares Esqueléticas/patologia , NF-kappa B/biossíntese , Óxido Nítrico/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Músculo Quadríceps/patologia , Distribuição Aleatória , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Ferimentos não Penetrantes/patologiaRESUMO
Entamoeba histolityca produces the monocyte locomotion inhibitory factor (MLIF), a pentapeptide with powerful anti-inflammatory properties. MLIF may regulate trauma-induced inflammation through the effects it exerts directly or indirectly on immune cells, modulating the production and/or expression of the cytokines involved in the inflammatory processes that occur after damage. The aim of the present study was to evaluate the effect of MLIF on production of pro/anti-inflammatory cytokines after contusion in the rat tibia. Fifty-four Wistar rats were subjected to controlled contusion with a special guillotine-type device, and 36 rats were injected with MLIF or tenoxicam into the tibia. Eighteen animals received saline; the animals were sacrificed 24 or 48 hours after injection. Cytokine mRNA and protein production were determined by reverse transcriptase-polymerase chain reaction (RT-PCR), immunofluorescence, and hematoxylin-eosin staining was performed to visualize cellular infiltration in the rats' injured tissue. Expression levels of the cytokines interferon gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and transforming growth factor-beta (TGF-ß) mRNA were inhibited significantly by MLIF at 24 hours post-contusion. MLIF significantly increased the expression levels of IL-10 at 24 hours compared with tenoxicam or the control group. These changes were associated with a significant decrease in protein production levels of TNF-α, IFN-γ, IL-6 and TGF-ß at 24 hours. Histological evaluation showed the presence of infiltration by neutrophils, monocytes and leucocytes in control tissues. This infiltration was decreased after MLIF administration, and intense infiltration was observed in tenoxicam-treated group. MLIF inhibited the expression of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokine IL-10.
Assuntos
Anti-Inflamatórios/farmacologia , Contusões/tratamento farmacológico , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Oligopeptídeos/farmacologia , Tíbia/efeitos dos fármacos , Animais , Contusões/metabolismo , Inflamação/metabolismo , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Masculino , Piroxicam/análogos & derivados , Piroxicam/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Tíbia/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Muscle injuries trigger an inflammatory process, releasing important biochemical markers for tissue regeneration. The use of non-steroidal anti-inflammatory drugs (NSAIDs) is the treatment of choice to promote pain relief due to muscle injury. NSAIDs exhibit several adverse effects and their efficacy is questionable. Photobiomodulation therapy (PBMT) has been demonstrated to effectively modulate inflammation induced from musculoskeletal disorders and may be used as an alternative to NSAIDs. Here, we assessed and compared the effects of different doses of PBMT and topical NSAIDs on biochemical parameters during an acute inflammatory process triggered by a controlled model of contusion-induced musculoskeletal injury in rats. Muscle injury was induced by trauma to the anterior tibial muscle of rats. After 1 h, rats were treated with PBMT (830 nm, continuous mode, 100 mW of power, 35.71 W/cm2; 1, 3, and 9 J; 10, 30, and 90 s) or diclofenac sodium (1 g). Our results demonstrated that PBMT, 1 J (35.7 J/cm2), 3 J (107.1 J/cm2), and 9 J (321.4 J/cm2) reduced the expression of tumor necrosis factor alpha (TNF-α) and cyclooxygenase-2 (COX-2) genes at all assessed times as compared to the injury and diclofenac groups (p < 0.05). The diclofenac group showed reduced levels of COX-2 only in relation to the injury group (p < 0.05). COX-2 protein expression remained unchanged with all therapies except with PBMT at a 3-J dose at 12 h (p < 0.05 compared to the injury group). In addition, PBMT (1, 3, and 9 J) effectively reduced levels of cytokines TNF-α, interleukin (IL)-1ß, and IL-6 at all assessed times as compared to the injury and diclofenac groups (p < 0.05). Thus, PBMT at a 3-J dose was more effective than other doses of PBMT and topical NSAIDs in the modulation of the inflammatory process caused by muscle contusion injuries.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Contusões/tratamento farmacológico , Contusões/radioterapia , Terapia com Luz de Baixa Intensidade/métodos , Músculo Esquelético/lesões , Administração Tópica , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Biomarcadores/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Diclofenaco/farmacologia , Diclofenaco/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/efeitos da radiação , Ratos Wistar , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Our previous in vitro results demonstrated that 11-dehydrosinulariolide significantly reduced 6-hydroxydopamine-induced cytotoxicity and apoptosis in a human neuroblastoma cell line, SH-SY5Y, and suppressed the expression of inducible NO synthase (iNOS) and cyclooxygenase 2 in lipopolysaccharide-stimulated macrophage cells. The neuroprotective and anti-inflammatory effects of 11-dehydrosinulariolide may be suitable for treating spinal cord injury (SCI). METHODS: In the present study, Wistar rats were pretreated with 11-dehydrosinulariolide or saline through intrathecal injection after a thoracic spinal cord contusion injury induced using a New York University (NYU) impactor. The apoptotic cells were assessed using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expression and localization of proinflammatory, apoptosis-associated and cell survival-related pathway proteins were examined through immunoblotting and immunohistochemistry. RESULTS: 11-Dehydrosinulariolide attenuated SCI-induced cell apoptosis by upregulating the antiapoptotic protein Bcl-2 and cell survival-related pathway proteins p-Akt and p-ERK, 8 h after SCI. Furthermore, the transcription factor p-CREB, which regulates Bcl-2 expression, was upregulated after 11-dehydrosinulariolide treatment. On day 7 after SCI, 11-dehydrosinulariolide exhibited an anti-inflammatory effect, attenuating SCI-induced upregulation of the inflammatory proteins iNOS and tumor necrosis factor-α. 11-Dehydrosinulariolide also induced an increase in the expression of arginase-1 and CD206, markers of M2 microglia, in the injured spinal cord on day 7 after SCI. Thus, the anti-inflammatory effect of 11-dehydrosinulariolide may be related to the promotion of an alternative pathway of microglia activation. CONCLUSION: The results show that 11-dehydrosinulariolide exerts antiapoptotic effects at 8 h after SCI and anti-inflammatory effects at 7 days after SCI. We consider that this compound may be a promising therapeutic agent for SCI.
Assuntos
Antozoários/química , Anti-Inflamatórios não Esteroides/uso terapêutico , Apoptose/efeitos dos fármacos , Diterpenos/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Proteínas Reguladoras de Apoptose/biossíntese , Proteínas Reguladoras de Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Contusões/tratamento farmacológico , Diterpenos/química , Marcação In Situ das Extremidades Cortadas , Locomoção , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Wistar , Recuperação de Função Fisiológica , Transdução de Sinais/efeitos dos fármacos , Traumatismos da Medula Espinal/psicologiaRESUMO
BACKGROUND: The present objective was to investigate endogen erythropoietin (EPO) level and relationship to oxidative stress within the first 24 hours of blunt chest trauma-induced pulmo-nary contusion (PCn) in a rat model. METHODS: Thirty-five rats were divided into 3 groups. In the baseline control group (BC, n=7), rats were uninjured and untreated. In the positive control group (PC, n=21) rats were injured but untreated. In the EPO-24 group (n=7), rats were injured and a single dose of intra-peritoneal EPO (5000 IU/kg) was administered immediately after lung injury. The PC group was divided into 3 subgroups: PC-6 (n=7), PC-12 (n=7), and PC-24 (n=7). The BC group was subjected to thoracotomy, and the right lung was harvested. The PC subgroups were eu-thanized at 6, 12, and 24 hours after injury, respectively. The EPO-24 group was euthanized at the 24th hour after injury. Lung samples were obtained, levels of malondialdehyde (MDA) and EPO were analyzed, and activities of superoxide dismutase (SOD) and catalase (CAT) were then measured in homogenized lung tissue samples. Histologic damage to lung tissue in the BC group, the EPO-24 group, and PC subgroup euthanized at the 24th hour after injury were scored by a single pathologist blinded to group assignation. RESULTS: Mean MDA levels, as well as SOD and CAT activities, of the BC and EPO-24 groups were significantly lower than those of the PC group (p<0.005). Mean EPO concentra-tion of the PC group was significantly higher than that of the BC group (p<0.005). Lung tis-sue damage scores measured at 24 hours after injury were significantly lower in the EPO-24 group than in the PC group (p<0.005). CONCLUSION: In the present PCn rat model, EPO concentrations, as well as SOD and CAT levels, were high in lung tissue, when measured at 24 hours after PCn. When administered early after chest trauma, EPO significantly attenuated oxidative damage and tissue damage in the early phase, as assessed by biochemical markers and histologic scoring.
Assuntos
Eritropoetina/farmacologia , Lesão Pulmonar/tratamento farmacológico , Pulmão/efeitos dos fármacos , Ferimentos não Penetrantes/tratamento farmacológico , Animais , Contusões/sangue , Contusões/tratamento farmacológico , Modelos Animais de Doenças , Eritropoetina/administração & dosagem , Eritropoetina/sangue , Infusões Parenterais , Lesão Pulmonar/sangue , Masculino , Ratos , Ratos Sprague-Dawley , Ferimentos não Penetrantes/sangueRESUMO
The therapeutic efficiency of an anti-inflammatory agent, dexamethasone (DXM), and a nitric oxide synthase (NOS) inhibitor, Nitro-L-arginine methyl ester (L-NAME), in lung tissue injury after lung contusion was investigated. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), YKL-40, an inflammatory peptide, inducible NOS (iNOS), and Clara cell protein 16 (CC-16) were evaluated. Immunohistochemical analyses were also performed, and the lung tissue was examined histopathologically. The study consisted of eight groups of Sprague-Dawley rats (n = 10 in each group), weighing 250-300 g: (1) control, (2) contusion, (3) control + DXM, (4) contusion + DXM, (5) control + L-NAME (6) contusion + L-NAME, (7) control + DXM + L-NAME, and (8) contusion + DXM + L-NAME. A previously developed lung contusion model was used, in addition to the control group. The rats were administered DXM and L-NAME intraperitoneally (i.p.) at doses of 15 and 60 mg/kg/day, respectively. DXM and L-NAME administration decreased the iNOS level in the contusion groups. DXM increased the levels of YKL-40 and IL-10 in both the control and contusion groups, with higher levels in the contusion groups. L-NAME increased the serum level of IL-10 in the lung contusion groups. DXM increased the synthesis of CC-16 in the control and contusion groups. The combined use of a high-dose steroid and NOS inhibitor resulted in the death of the rats. Steroids can increase the level of cytokines, such as YKL-40 and IL-10, and the synthesis of CC-16 and prevent pneumonia, ALI/ARDS, and sepsis in lung contusion.