N-acetylcysteine effects on a murine model of chronic critical limb ischemia.

During chronic limb ischemia, oxidative damage and inflammation are described. Besides oxidative damage, the decrease of tissue oxygen levels is followed by several adaptive responses. The purpose of this study was to determine whether supplementation with N-acetylcysteine (NAC) is effective in an animal model of chronic limb ischemia. Chronic limb ischemia was induced and animals were treated once a day for 30 consecutive days with NAC (30mg/kg). After this time clinical scores were recorded and soleus muscle was isolated and lactate levels, oxidative damage and inflammatory parameters were determined. In addition, several mechanisms associated with hypoxia adaptation were measured (vascular endothelial growth factor - VEGF and hypoxia inducible factor - HIF levels, ex vivo oxygen consumption, markers of autophagy/mitophagy, and mitochondrial biogenesis). The adaptation to chronic ischemia in this model included an increase in muscle VEGF and HIF levels, and NAC was able to decrease VEGF, but not HIF levels. In addition, ex vivo oxygen consumption under hypoxia was increased in muscle from ischemic animals, and NAC was able to decrease this parameter. This effect was not mediated by a direct effect of NAC on oxygen consumption. Ischemia was followed by a significant increase in muscle myeloperoxidase activity, as well as interleukin-6 and thiobarbituric acid reactive substances species levels. Supplementation with NAC was able to attenuate inflammatory and oxidative damage parameters, and improve clinical scores. In conclusion, NAC treatment decreases oxidative damage and inflammation, and modulates oxygen consumption under hypoxic conditions in a model of chronic limb ischemia.

Evaluation of the role of the cannabidiol system in an animal model of ischemia/reperfusion kidney injury.

OBJECTIVE: This work aimed to investigate the effects of the administration of cannabidiol in a kidney ischemia/reperfusion animal model. METHODS: Kidney injury was induced by 45 minutes of renal ischemia followed by reperfusion. Cannabidiol (5mg/kg) was administered immediately after reperfusion. RESULTS: Ischemia/reperfusion increased the IL-1 and TNF levels, and these levels were attenuated by cannabidiol treatment. Additionally, cannabidiol was able to decrease lipid and protein oxidative damage, but not the nitrite/nitrate levels. Kidney injury after ischemia/reperfusion seemed to be independent of the cannabidiol receptor 1 and cannabidiol receptor 2 (CB1 and CB2) expression levels, as there was no significant increase in these receptors after reperfusion. CONCLUSION: The cannabidiol treatment had a protective effect against inflammation and oxidative damage in the kidney ischemia/reperfusion model. These effects seemed to be independent of CB1/CB2 receptor activation.

Correlation of acute phase inflammatory and oxidative markers with long-term cognitive impairment in sepsis survivors rats.

Oxidative damage and inflammation occur early in the brain after sepsis and are resolved when long-term cognitive impairment occurs. There is no information of a direct relation between acute levels of brain inflammation and oxidative damage and long-term cognitive deficits. We hypothesized that higher levels of early oxidative damage and inflammation are followed by long-term cognitive deficits, and this is related to a decrease in the levels of brain-derived neurotropic factor (BDNF). Wistar rats were subjected to sham operation or cecal ligation and perforation and the cerebrospinal fluid (CSF) was obtained 6 and 24 h after the determination of thiobarbituric acid-reactive species, interleukin 1 (IL-1), IL-10, and tumor necrosis factor α (TNF-α). Animals were followed until 30 days after surgery and were subjected to the step-down inhibitory avoidance (IA) task, and the hippocampus levels of BDNF were determined. At 6 h, higher CSF levels of thiobarbituric acid-reactive species and TNF-α were observed in septic animals that had a better performance in the IA task and presented higher BDNF levels in the hippocampus. At 24 h, higher CSF levels of IL-1ß and TNF-α were observed in septic animals that had a worse performance in the IA task, and this was associated with lower BDNF levels. The persistence of brain inflammation during the acute phase of sepsis is associated with long-term hippocampus levels of BDNF and memory impairment in sepsis survivors.

Avaliação do papel do sistema canabidiol em um modelo de lesão renal por isquemia/reperfusão em animais / Evaluation of the role of the cannabidiol system in an animal model of ischemia/reperfusion kidney injury

RESUMO Objetivo: Investigar os efeitos da administração de canabidiol em um modelo de isquemia/reperfusão renal em animais. Métodos: Foi induzida uma lesão renal, por meio de 45 minutos de isquemia renal seguida por reperfusão. Administrou-se canabidiol (5mg/kg) imediatamente após a reperfusão. Resultados: A isquemia/reperfusão aumentou os níveis de interleucina 1 e fator de necrose tumoral, o que foi atenuado pelo tratamento com canabidiol. Além disso, o canabidiol foi capaz de diminuir o dano oxidativo de lipídios e proteínas, mas não os níveis de nitrito/nitrato. A lesão renal após isquemia/reperfusão pareceu ser independente da expressão dos receptores canabidiol-1 e canabidiol-2, já que não houve aumento significante desses receptores após a reperfusão. Conclusão: O tratamento com canabidiol teve um efeito protetor contra a inflamação e o dano oxidativo em um modelo de isquemia/reperfusão renal. Esses efeitos parecem não ocorrer via ativação dos receptores canabidiol-1/canabidiol-2.

ABSTRACT Objective: This work aimed to investigate the effects of the administration of cannabidiol in a kidney ischemia/reperfusion animal model. Methods: Kidney injury was induced by 45 minutes of renal ischemia followed by reperfusion. Cannabidiol (5mg/kg) was administered immediately after reperfusion. Results: Ischemia/reperfusion increased the IL-1 and TNF levels, and these levels were attenuated by cannabidiol treatment. Additionally, cannabidiol was able to decrease lipid and protein oxidative damage, but not the nitrite/nitrate levels. Kidney injury after ischemia/reperfusion seemed to be independent of the cannabidiol receptor 1 and cannabidiol receptor 2 (CB1 and CB2) expression levels, as there was no significant increase in these receptors after reperfusion. Conclusion: The cannabidiol treatment had a protective effect against inflammation and oxidative damage in the kidney ischemia/reperfusion model. These effects seemed to be independent of CB1/CB2 receptor activation.