Diabetes mellitus triggers oxidative stress in the liver of alloxan-treated rats: a mechanism for diabetic chronic liver disease

PURPOSE: To investigate whether Diabetes mellitus chemically induced by alloxan is capable of changing, in the long term, the oxidative balance in the liver tissue of rats. METHODS: Sixty male Wistar rats, weighing 250-280g, were randomly distributed into two experimental groups: NG - 30 non-diabetic control rats; DG - 30 alloxan- induced diabetic rats without any treatment for the disease. Each group was further divided into three subgroups containing ten rats each, which were sacrificed after one, three and six months of follow-up, respectively. Blood glucose, urinary glucose, glycosylated hemoglobin and insulin were determined in the plasma of all animals at the beginning of the experiment and prior to all sacrifice periods. The concentrations of lipid hydroperoxides (HP) and the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were also measured in the liver tissue of all animals. RESULTS: Rats from the DG group showed high levels of blood glucose, urinary glucose, and glycosylated hemoglobin, with significantly lower plasma insulin levels than those observed in NG rats (p<0.001). Diabetic animals also showed increased concentration of HP free radicals in the liver tissue as compared to those shown by NG animals after one, three and six months of follow-up. In contrast, the antioxidant activity of the enzymes SOD, CAT and GSH-Px was significantly reduced in all follow-up periods (p<0.01). CONCLUSIONS: Diabetes determines oxidative stress in the liver, which is characterized by increased concentration of reactive oxygen species (ROS) in tissue and significant reduction in their antioxidant defenses. Such oxidative unbalance in the liver cells may play a relevant role in the genesis of the diabetic chronic liver disease, including the non-alcoholic fatty liver disease and its occasional progression to steatohepatitis and cirrhosis.(AU)

Experimental diabetes exacerbates skin transplant rejection in rats

PURPOSE: To investigate the effect of chronic experimental diabetes on skin allografts in rats as a simple model that could clarify some basic aspects and mechanisms involved in transplant rejection in diabetes compared to normal animals. METHODS: Skin grafting was performed with fragments of tail skin from sex matched non diabetic Wistar rats engrafted onto the thoracic area of diabetic and non diabetic recipients. Grafts were scored for rejection every other day and were removed on day 14. Skin grafts were graded according to the following itens: no rejection; or rejection including: acute, chronic and humoral and/or cellular rejection. Statistical analysis was performed using JMP 5.1 software with ANOVA test. Diabetes was induced with IV injection of alloxan 40 mg/kg. RESULTS: Inflammatory vascular infiltrate compromising the endothelium with areas of fibrinoid necrosis and thrombosis characteristics of acute humoral rejection and subendothelial lymphocyte infiltrate typical of acute cellular rejection were significantly (p<0.003) higher in diabetic than in non diabetic recipients as the inflammatory infiltrate in the epidermis (p<0.002). CONCLUSION: Skin transplant acute rejection from chronic alloxan diabetic rats to normal tissue was significantly more intense than the acute rejection between normal rats.(AU)

Simvastatin attenuates neutrophil recruitment in one-lung ventilation model in rats

PURPOSE: To investigate the anti-inflammatory effects of simvastatin in rats undergoing one-lung ventilation (OLV) followed by lung re-expansion. METHODS: Male Wistar rats (n=30) were submitted to 1-h OLV followed by 1-h lung re-expansion. Treated group received simvastatin (40 mg/kg for 21 days) previous to OLV protocol. Control group received no treatment or surgical/ventilation interventions. Measurements of pulmonary myeloperoxidase (MPO) activity, pulmonary protein extravasation, and serum levels of cytokines and C-reactive protein (CRP) were performed. RESULTS: OLV significantly increased the MPO activity in the collapsed and continuously ventilated lungs (31% and 52% increase, respectively) compared with control (p<0.05). Treatment with simvastatin significantly reduced the MPO activity in the continuously ventilated lung but had no effect on lung edema after OLV. The serum IL-6 and CRP levels were markedly higher in OLV group, but simvastatin treatment failed to affect the production of these inflammatory markers. Serum levels of IL-1β, TNF-α and IL-10 remained below the detection limit in all groups. CONCLUSIONS: In an experimental one-lung ventilation model pre-operative treatment with simvastatin reduces remote neutrophil infiltration in the continuously ventilated lung. Our findings suggest that simvastatin may be of therapeutic value in OLV-induced pulmonary inflammation deserving clinical investigations.(AU)

Ischemic preconditioning attenuates remote pulmonary inflammatory infiltration of diabetic rats with an intestinal and hepatic ischemia-reperfusion injury

PURPOSE: To assess ischemic preconditioning (IPC) effects in pulmonary lesion in intestinal and hepatic ischemia-reperfusion (IR) injury models using diabetic rats. METHODS: Diabetes (DM) was induced in 28 male Wistar rats by alloxan (42 mg/kg, IV). After 28 days, severe DM rats were submitted to intestinal or hepatic IR injury with or without IPC. Intestinal IR (30 min of mesenteric artery occlusion and 30 min of reperfusion; n=6) and IPC groups (10 min ischemia, 10 min reperfusion, followed by intestinal IR; n=6), and Hepatic IR (30 min of hepatic pedicle occlusion and 30 min of reperfusion; n=5) and IPC groups (10 min ischemia, 10 min reperfusion, followed by hepatic IR; n=5), were compared to DM rats group (n=6). Plasmatic lactate, glycemia were measured before and after IR injury. Histomorphology of lung was performed counting inflammatory cells. Data was expressed in mean± SE. P<0.05. RESULTS: Glycemia and lactate were similar among groups. IPC did not interfere in these parameters. On histological evaluation, IR increased inflammatory cells infiltration in pulmonary parenchyma compared to control in both IR injury models. IPC attenuated inflammatory infiltration in lungs. CONCLUSION: Ischemic preconditioning protects against remote ischemia-reperfusion injury in lung on intestinal or hepatic ischemia-reperfusion model with acute diabetes.(AU)