Pancreas transplantation prevents cellular oxidative stress in kidneys of alloxan-induced diabetic rats.

PURPOSE: Oxidative stress is one of the most important mechanisms to explain genesis of the complications in the chronic progression of diabetes. In this investigation we studied the effects of pancreas transplantation (PT) on the imbalance caused by excessive production of free oxygen radicals by antioxidant defenses of rats with serious chronic hyperglycemia induced by alloxan. METHODS: Ninety inbred male Lewis rats were randomly distributed into three groups: NC-30 nondiabetic controls; DC-30 diabetic controls without any treatment; PT-30 diabetic rats undergoing syngeneic PT from normal donor Lewis rats. Each experimental group was then split into three subgroups of 10 animals for sacrifice after 1, 3, or 6 months. Clinical and laboratory parameters from all rats as well as lipid hydroperoxide (LPO) concentrations and renal tissue enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were recorded for all rats. RESULTS: Successful PT corrected clinical and laboratory alterations in diabetic rats with sustained normoglycemia throughout the study. A significant increase in LPO concentration and a marked reduction in SOD and CAT enzyme activity were observed in DC rats; there was no significant variation in renal tissue GSH-Px in this group. However, alterations in DC rats were completely restored from 1st month after PT; all evaluated enzyme levels did not significantly differ (P < .01) from those in NC controls. CONCLUSION: Successful PT controlled cellular oxidative stress in diabetic kidneys, which may prevent chronic lesions.

Temporal relationship between successful pancreas transplantation and control of ocular complications in alloxan-induced diabetic rats.

PURPOSE: The impact of pancreas transplantation (PT) on the progression of eye disease is still controversial. This study evaluated the course of retinopathy in transplanted rats in two different diabetic stages. METHODS: Sixty inbred male Lewis rats were assigned to four experimental groups: NC-15 nondiabetic control rats; DC-15 untreated diabetic control rats; PT1-15 diabetic rats that received syngeneic pancreas transplants 2 weeks after alloxan diabetes induction; PT2-15 diabetic rats that received pancreas transplants 12 weeks after diabetes onset. Clinical and laboratory parameters and lens opacity were examined in all rats prior to treatment and at 1-, 6-, and 12-months follow-up. Nucleated eyes from five rats in each group processed for ultrastructural study of the retinal at 6 and 12 months after PT or at follow-up. RESULTS: Cataracts were observed in 20%, 60%, and 100% of DC rats at 1-, 6-, and 12-months follow-up, respectively. Early PT (2 weeks) significantly reduced the prevalence of this complication but not late (12 weeks) PT. PT1 rats also showed improved ultrastructure of the superficial and deep capillary plexuses of the retina, and of Müller cells, compared with DC and PT2. In the last group, retinopathy continued to evolve despite successful PT. CONCLUSION: Our results suggested that prevention of diabetic ocular lesions by PT was closely dependent on earlier performance of the procedure.

Induction of short gut syndrome and transplantation in a porcine model.

UNLABELLED: Experimental models in small animals have been described for nutritional studies after small bowel transplantation for extensive resection. Herein, we compared the outcome of transplanted pigs that underwent transplantation after total small bowel resection (SBR) with controls without transplantation. METHODS: Twenty-one Landrace pigs (mean weight 30 kg) were assigned to 1 of 3 groups: group 1 (n = 6) underwent 80% SBR; group 2 (n = 9), total bowel resection; and group 3 (n = 6) total resection plus small bowel transplantation. Postoperative evaluation included biochemical analyses, weights, and evaluation of clinical status. Conventional endoscopies with graft biopsies were obtained every 4 days to assess rejection. RESULTS: Group 1 showed increased body weight after 3 weeks due to bowel adaptation, whereas groups 2 and 3 lost weight, an observation that correlated with biochemical analyses. Median survival in group 3 was 10 +/- 2 days; all hosts died of sepsis related to severe acute rejection. DISCUSSION: Short gut syndrome appeared in group 2 but not in group 1, where intestinal adaptation was observed by 4 weeks after the resection. Rejection was confirmed in group 3 using conventional endoscopy plus biopsies and at necropsy. CONCLUSION: Total bowel resection is an adequate model for short gut syndrome in pigs, rejection can be readily identified by using conventional endoscopy.

Long-term effects of insulin therapy, islet transplantation, and pancreas transplantation in the prevention of glomerular changes in kidneys of alloxan-induced diabetic rats.

Groups of inbred alloxan-induced diabetic rats were treated with insulin (I), islets (IT), or pancreas transplantation (PT). Nondiabetic (N) and untreated diabetic (D) control groups were concurrently included. Each group was divided into five subgroups of 10 rats and killed after follow-up of 1, 3, 6, 9, and 12 months. Clinical and laboratory parameters were recorded, and kidney ultrastructural and morphometric analyses performed in each 12-month subgroup, namely glomerular basement membrane (GM) thickening, podocyte number, and number/extension of slit diaphragms (S). Rats from the I group showed poor metabolic control of diabetes compared with N group control rats. However, successfully transplanted rats (IT and PT) had complete restoration to normal levels for all metabolic parameters. GM thickening was significantly higher in diabetic compared with control rats. In contrast, the numbers of podocytes and slits as well as slit extensions were significantly decreased. Insulin therapy did not prevent any alterations upon comparison of diabetic vs control rats. Despite good metabolic control in IT rats, the degree of kidney lesion control never compared with that achieved in PT rats. In this group all glomerular changes were similar to the age-dependent lesions observed in control rats. We conclude that either IT or PT may be a good option for diabetes treatment, although pancreas transplantation seems to be the most effective treatment to control chronic complications.