Cytoprotective effects of alpha-tocopherol on ischemia/reperfusion injury in rat liver: biochemical and histological evaluation.
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Biomedical subjects
Publications and source records attributed to D J Fagundes.
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The objective of this study was to evaluate the effect of ischemic preconditioning upon lesions produced by ischemia-reperfusion of the small intestine. Thirty EPM-1 Wistar rats were randomly distributed into three groups: ischemic preconditioning (IPC; n = 12), ischemia-reperfusion (I/R; n = 12), and control (C; n = 6). Laparotomy permitted isolation of the mesenteric artery for clamping. The animals were heparinized and hydrated. IPC was induced by: 10 minutes of ischemia followed by 10 minutes of reperfusion and then 50 minutes ischemia followed by another 30 minutes reperfusion. Group I/R was submitted to the same protocol except for the 20 minutes of preconditioning. Group C animals underwent only laparotomy for 100 minutes. After reperfusion small intestine fragments were examined histologically. Blood samples were obtained to measure LDH and lactate prior to euthanasia. Lactate values were significantly lower in the IPC as compared to I/R group, 39 versus 67 mg/dL, respectively (P < or =.05). However, neither IPC (grade 3) lesions of the mucosa versus I/R (grade 4) nor LDH values (PCI = 680, I/R = 873 U/L) were statistically different. Thus No morphological evidence of protection was observed following ischemic preconditioning.
This study investigated the effect of gangliosides (Gang) on small bowel microcirculation and animal survival after normothermic intestinal ischemia-reperfusion injury. Five adult male EPM-1 Wistar rats in each of three groups received FK506 (0.2 mg/kg), Gang (3 mg/kg), or vehicle (at same volume) either 24 or 12 hours prior to the experiment. The animals were anesthetized intramuscularly with ketamine (60 mg/kg) and xylazine (10 mg/kg) and hydrated with 80 mL/kg of prewarmed saline solution delivered subcutaneously before the ischemic insult and 40 mL/kg at 1 hour after reperfusion. Under anesthesia, they underwent a laparotomy with clamping of the superior mesenteric artery (SMA) at its origin for 75 minutes. Microcirculation was evaluated with a laser Doppler flowmeter, 5 minutes before ischemia (baseline) and reperfusion (ischemia), and 20, 40, and 60 minutes after reperfusion. Animal survival was observed up to 24 hours. Small bowel flow measured before ischemia was considered to be the baseline level (100%). After SMA occlusion a significant reduction in microcirculatory tissue perfusion to about 8% was observed in all groups. At 20, 40, and 60 minutes of reperfusion treatment with Gang (77%, 81%, and 100%) or FK506 (70%, 85%, and 98%) promoted better recovery of the intestinal microcirculation when compared to the control group (45%, 72%, and 75%). Concerning animal survival there was no difference between groups (just one animal from each group, Gang and FK506, survived up to 24 hours). Based on our data we conclude that Gang and FK506 improve intestinal microcirculation in ischemia-reperfusion injury but do not change animal survival after severe ischemia.
The present study was carried out in order to determine the effect of lung resection on the frequency of infections in alloxan-diabetic rats. Adult female Wistar rats were injected with alloxan (40 mg/kg, iv) to induce diabetes mellitus (group D; N = 45) or with vehicle (1.0 ml/kg, iv) to be used as controls (group C; N = 45). Thirty-six days after receiving alloxan both groups were randomly divided into three subgroups: no operation (NO; N = 15), sham operation (SO; N = 15), and left pneumonectomy (PE; N = 15). The rats were sacrificed 36 days after surgery and their lungs were examined microscopically and macroscopically. The occurrence of thoracic wall infection, thoracic wall abscess, lung abscess and pleural empyema was similar in groups D and C. In contrast, the overall infection rate was higher (P<0.05) in the diabetic rats (SO-D and PE-D subgroups, but not in the NO-D subgroup). Considering that the overall infection rate was similar in the SO-D and PE-D subgroups, we suggest that surgery but not pneumonectomy was related to the higher prevalence of infection in diabetic rats.
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The study was performed to investigate possible alterations in oxygen consumption in an animal model with broad intestinal resection. Oxygen consumption and the thermal effect of a short meal were measured in rats subjected to short bowel syndrome. Four groups of rats were used. Group I was the control group, group II was sham operated, group III was submitted to 80% jejunum-ileum resection, and group IV was submitted to 80% jejunum-ileum resection with colon interposition. Ninety days after surgery, oxygen consumption was measured over a period of 6 h with the animals fasted overnight. The thermal effect of feeding was determined in another session of oxygen consumption measurement in animals fasted for 12 h. A 12-kcal meal was then introduced into the animal chamber and oxygen consumption was measured for a further 4 h. No differences in fasting oxygen consumption or in the thermal effect of the meal were detected among the groups studied. It is concluded that short bowel syndrome does not affect the overall energy expenditure of rats.
We have previously shown that the intrapleural injection of mitozantrone but not bleomycin resulted in pleural fibrosis. Mechlorethamine hydrochloride (nitrogen mustard) was used extensively in the past to control malignant effusions, with relatively good success. The objective of this study was to determine if the intrapleural injection of nitrogen mustard would produce pleural sclerosis in our experimental model in rabbits. We therefore evaluated sclerosing capabilities of nitrogen mustard as well as those of cytarabine and dacarbazine. Nitrogen mustard (0.4 and 0.8 mg x kg(-1)), cytarabine (3, 6 and 20 mg x kg(-1)) and dacarbazine (4, 8 and 20 mg x kg(-1)) were instilled intrapleurally into anaesthetized rabbits. Twenty eight days after the instillation, the animals were killed, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of 0.8 mg x kg(-1) nitrogen mustard was effective in creating pleural fibrosis, either grossly or microscopically. The mean degree (scale 0-4) of gross pleurodesis in the rabbits that received 0.8 mg x kg(-1) nitrogen mustard was 3.2+/-1.0 and the mean degree of microscopic pleural fibrosis was 3.5+/-0.8. The intrapleural injection of 0.4 mg x kg(-1) nitrogen mustard and the different doses of cytarabine (3, 6 and 20 mg x kg(-1)) and dacarbazine (4, 8 and 20 mg x kg(-1)) were ineffective in producing pleurodesis. From this study, we conclude that the intrapleural injection of 0.8 mg x kg(-1) of nitrogen mustard produces clinically significant pleurodesis in rabbits. Consideration should be given to future clinical studies utilizing 0.6-0.8 mg x kg(-1) nitrogen mustard intrapleurally for the treatment of malignant pleural effusion.
One of the proposed surgical treatments of Short Bowel Syndrome is the interposition of a distal colon segment between two portions of the remnant small intestine. This method proved to reverse the nutritional disorders caused by this morbid entity. Surgical technique consisted in an 80% small bowel resection and the interposition of a 3 cm segment of distal colon between the remaining jejunum and ileum. After 70 days, the animals were reoperated and the interposed and the distal colon were isolated and tied. By using the method of rapid and successive absorptions of a glucose solution through the intestinal lumen, the relations between the absorption curves of the interposed and the normal colon could be drawn. Results show that the interposed colon segment absorbs more glucose (mean = 1.43 +/- 1.16 mg/dl) than the distal colon (mean = 0.37 +/- 0.29 mg/dl) and that its absorption pattern is similar to the small bowel rather than the colon. These results allow the use of this method for further studies in which the interposed colon adaptation is studied with other nutrients and/or under specific conditions.
An adaptation of the Sols and Ponz method for the study of glucose intestinal absorption was developed by considering the special conditions of our line research. The glucose absorption was studied in proximal jejunum, distal ileum and distal colon in Wistar rat. The main adaptations in the method for successive absorptions with intestinal perfusions in vivo were the length of the intestinal segment and the change of the pumping system. The results are very similar to those obtained with the original method.
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