Modeling Mediated Crossover Acute and Subacute Damage to the Pulmonary System During Systemic (Subcutaneous) Administration of Bleomycin in Mice to Test the Potential Therapeutic Effect of Polyphenols / Modelado del Daño Agudo y Subagudo Cruzado Mediado al Sistema Pulmonar Durante la Infección Sistémica (Subcutánea) de Administración de Bleomicina a Ratones para Probar el Posible Efecto Terapéutico de los Polifenoles

SUMMARY: The potential anti-inflammatory and antifibrotic activity of polyphenolic extracts of blueberry and grape was evaluated in a mouse model of lung damage induced by subcutaneous administration of bleomycin. The results of testing the polyphenolic extracts on two different systemic administration variants of bleomycin (intraperitoneal and subcutaneous) were compared. It was found that regardless of the method of bleomycin administration, indirect cross-acute and subacute damage to the pulmonary system was observed. Both patterns exhibited the same prevalence and severity. The administration of polyphenolic extracts of blueberry and grape to mice resulted in a significant decrease in theseverity of acute and subacute patterns of lung damage, suggesting their protective properties for the microcirculatory bed and a pronounced anti-inflammatory effect.

La potencial actividad antiinflamatoria y antifibrótica de los extractos polifenólicos de arándano y uva se evaluó en un modelo de daño pulmonar en ratón inducido por la administración subcutánea de bleomicina. Se compararon los resultados de las pruebas de los extractos polifenólicos en dos variantes diferentes de administración sistémica de bleomicina (intraperitoneal y subcutánea). Se encontró que, independientemente del método de administración de bleomicina, se observaba daño indirecto cruzado, agudo y subagudo al sistema pulmonar. Ambos patrones exhibieron la misma prevalencia y gravedad. La administración de extractos polifenólicos de arándano y uva a ratones dio como resultado una disminución significativa en la gravedad de los patrones agudos y subagudos de daño pulmonar, lo que sugiere sus propiedades protectoras del lecho micro- circulatorio y un efecto antiinflamatorio pronunciado.

Local and systemic effects of fibrin and cyanoacrylate adhesives on lung lesions in rabbits

OBJECTIVES: Tissue adhesives can be used to prevent pulmonary air leaks, which frequently occur after lung interventions. The objective of this study is to evaluate local and systemic effects of fibrin and cyanoacrylate tissue adhesives on lung lesions in rabbits. METHODS: Eighteen rabbits were submitted to videothoracoscopy + lung incision alone (control) or videothoracoscopy + lung incision + local application of fibrin or cyanoacrylate adhesive. Blood samples were collected and assessed for leukocyte, neutrophil and lymphocyte counts and interleukin-8 levels preoperatively and at 48 hours and 28 days post-operatively. After 28 days, the animals were euthanized for gross examination of the lung surface, and lung fragments were excised for histopathological analysis. RESULTS: Fibrin and cyanoacrylate produced similar adhesion scores of the lung to the parietal pleura. Microscopic analysis revealed uniform low-cellular tissue infiltration in the fibrin group and an intense tissue reaction characterized by dense inflammatory infiltration of granulocytes, giant cells and necrosis in the cyanoacrylate group. No changes were detected in the leukocyte, neutrophil or lymphocyte count at any time-point, while the interleukin-8 levels were increased in the fibrin and cyanoacrylate groups after 48 hours compared with the pre-operative control levels (p<0.01). CONCLUSION: Both adhesive agents promoted normal tissue healing, with a more pronounced local inflammatory reaction observed for cyanoacrylate. Among the serum markers of inflammation, only the interleukin-8 levels changed post-operatively, increasing after 48 hours and decreasing after 28 days to levels similar to those of the control group in both the fibrin and cyanoacrylate groups.

Angiotensin- (1-7) inhibits inflammation and oxidative stress to relieve lung injury induced by chronic intermittent hypoxia in rats

Obstructive sleep apnea is associated with inflammation and oxidative stress in lung tissues and can lead to metabolic abnormalities. We investigated the effects of angiotensin1–7 [Ang-(1–7)] on lung injury in rats induced by chronic intermittent hypoxia (CIH). We randomly assigned 32 male Sprague-Dawley rats (180–200 g) to normoxia control (NC), CIH-untreated (uCIH), Ang-(1–7)-treated normoxia control (N-A), and Ang-(1–7)-treated CIH (CIH-A) groups. Oxidative stress biomarkers were measured in lung tissues, and expression of NADPH oxidase 4 (Nox4) and Nox subunits (p22phox, and p47phox) was determined by Western blot and reverse transcription-polymerase chain reaction. Pulmonary pathological changes were more evident in the uCIH group than in the other groups. Enzyme-linked immunosorbent assays and immunohistochemical staining showed that inflammatory factor concentrations in serum and lung tissues in the uCIH group were significantly higher than those in the NC and N-A groups. Expression of inflammatory factors was significantly higher in the CIH-A group than in the NC and N-A groups, but was lower than in the uCIH group (P<0.01). Oxidative stress was markedly higher in the uCIH group than in the NC and N-A groups. Expression of Nox4 and its subunits was also increased in the uCIH group. These changes were attenuated upon Ang-(1–7) treatment. In summary, treatment with Ang-(1-7) reversed signs of CIH-induced lung injury via inhibition of inflammation and oxidative stress.

A comparative study of pentoxifylline effects in adult and aged rats submitted to lung dysfunction by thermal injury

PURPOSE: To investigate the protective effects of pentoxifylline against lung injury observed after dorsal scald in aged animals. METHODS: Adult (eight months old) and aged (20 months old) rats were subjected to thermal injury or sham procedure. The six hours post-trauma animals received pentoxifylline and after 24 hours were euthanatized and lung tissue samples collectedted. The bronchoalveolar lavage fluid was evaluated for total protein content and tumor necrosis factor-alpha cytokine. Malondialdehyde and myeloperoxidase activety in the lung homogenate were measured and a histological lung examination was undertaken. RESULTS: Burn injury induced oxidative stress in lung homogenate was higher in elderly-burned rats compared to adult-burned rats (p<0.001). Total protein and cytokine in bronchoalveolar lavage increased in the elderly-burned group when compared to the adult-burned group (p<0.001). All parameters decreased in bolth groups treated with pentoxifylline (p<0.05). CONCLUSIONS: The injury was augmented in elderly rats when compared to adult rats. Damage was reduced with the use of pentoxifylline, however further studies are needed to evaluate the dose-response of the drug.

Cyclophosphamide dose: how much is needed to win the war against paraquat poisoning?

No abstract available.

Effect of glutamine on the total antioxidant system of rats subjected to renal ischemia and reperfusion / Efeito da glutamina no sistema antioxidante total de ratos submetidos a isquemia e reperfusão renal

PURPOSE: To evaluate the protective effects of glutamine administered before renal ischemia-reperfusion on plasma antioxidant protection, and lung and renal tissue injury. METHODS: 33 rats underwent right nephrectomy. On the eighth postoperative day, animals were randomized into three groups (n=11): glutamine, control and sham. Each group of animals received, by gavage, a particular diet for 7 days. On day 14 following nephrectomy, the animals were subjected to left renal ischemia-reperfusion. After this, blood samples were collected and the animals were killed. At necropsy the kidney and lung were removed for histology. RESULTS: The levels of total antioxidant capacity were higher in the glutamine group and control group compared with the sham group. The levels of glutathione peroxidase in both the sham and glutamine groups were higher when compared with the control group (p<0.05). The level of superoxide dismutase in the sham group was clearly higher than that in the glutamine and control groups. Histological examination showed no differences between the three groups. CONCLUSION: Prior intake of glutamine improves total antioxidant capacity and increases glutathione peroxidase levels in rats subjected to renal ischemia-reperfusion.

OBJETIVO: Avaliar os efeitos na proteção antioxidante plasmática e na lesão tecidual renal e pulmonar da glutamina oral administrada precedendo a isquemia/ reperfusão renal. MÉTODOS: Trinta e três ratos foram submetidos à nefrectomia à direita. No oitavo dia de pós-operatório, os animais foram randomizados em três grupos (n=11): glutamina, controle e sham. Cada grupo de animal recebeu por gavagem uma dieta distinta por sete dias. Ao final do 14º dia da nefrectomia procedeu-se a isquemia renal esquerda e posterior reperfusão. A seguir procedeu-se a coleta de sangue, eutanásia e retirada do rim e pulmões para análise histológica. RESULTADOS: Os níveis de capacidade antioxidante total foram maiores no grupo glutamina e grupo controle em relação ao grupo sham. Os níveis de glutationa peroxidase nos grupos sham e glutamina foram mais elevados quando comparados com o grupo controle (p<0,05). A dosagem de superóxido dismutase foi maior no grupo sham quando comparado com os grupos glutamina e controle. Não houve diferença na análise histológica do rim e pulmão entre os grupos. CONCLUSÃO: O uso de glutamina antecedendo a isquemia reperfusão renal melhora os níveis da capacidade antioxidante total e eleva a glutationa peroxidase em ratos submetidos a isquemia-reperfusão renal.

Granulocyte Colony Stimulating Factor Attenuates Hyperoxia-Induced Lung Injury by Down-Modulating Inflammatory Responses in Neonatal Rats

PURPOSE: Granulocyte colony stimulating factor (G-CSF) has been known to increase neutrophil production and have anti-inflammatory properties, but the effect of G-CSF on pulmonary system is in controversy. We investigated whether G-CSF treatment could attenuate hyperoxia-induced lung injury, and whether this protective effect is mediated by the down-modulation of inflammatory responses in a neonatal rat model. MATERIALS AND METHODS: Newborn Sprague-Dawley rats (Orient Co., Seoul, Korea) were subjected to 14 days of hyperoxia (90% oxygen) beginning within 10 h after birth. G-CSF (20 microg/kg) was administered intraperitoneally on the fourth, fifth, and sixth postnatal days. RESULTS: This treatment significantly improved hyperoxia-induced reduction in body weight gain and lung pathology such as increased mean linear intercept, mean alveolar volume, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling positive cells. Hyperoxia-induced activation of nicotinamide adenine dinucleotide phosphate oxidase, which is responsible for superoxide anion production, as evidenced by upregulation and membrane translocation of p67phox was significantly attenuated after G-CSF treatment, as were inflammatory responses such as increased myeloperoxidase activity and mRNA expression of transforming growth factor-beta. However, the attenuation of other proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 was not significant. CONCLUSION: In sum, G-CSF treatment significantly attenuated hyperoxia-induced lung injury by down-modulating the inflammatory responses in neonatal rats.