No abstract

No abstract

IGL-1 offered the same degree of safety and effectiveness as UW in our model of pig PT with 16 hr of cold ischemia.

Although the pathogenesis of ischemia reperfusion (IR) injury is based on complex mechanisms, free radicals play a central role. We evaluated membrane fluidity and lipid peroxidation during pancreas transplantation (PT) performed in 12 pigs (six donors and six recipients). Fluidity was measured by fluorescence spectroscopy, and malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations were used as an index of lipid oxidation. Pancreatic tissues were collected as follows: (A) donor, immediately before vascular clamping; (B) graft, following perfusion lavage with University of Wisconsin preservation fluid; (C) graft, after 16 h of cold ischemia; and (D) recipient, 30 min vascular postreperfusion. Fluidity and MDA and 4-HDA concentrations were similar in cases A, B, and C. However, there was significant membrane rigidity and increased lipid peroxidation after reperfusion (D). These findings suggest that reperfusion exaggerates oxidative damage and may account for the rigidity in the membranes of allografts during PT.

The protective in vivo effects of melatonin or pinoline on carbon tetrachloride (CCl(4))-induced oxidative damage were investigated in liver of rats and compared to rats injected only with CCl(4) (5 mL/kg body weight). Hepatic cell membrane fluidity, monitored using fluorescence spectroscopy, exhibited a significant decrease in animals exposed to CCl(4) compared to control rats. Increases in lipid and protein oxidation, as assessed by concentrations of malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA), and protein carbonylation, respectively, were also seen in hepatic homogenates of animals exposed to CCl(4). The administration of melatonin (10 mg/kg body weight) or pinoline injected 30 min before and 1 hr after CCl(4), fully prevented membrane rigidity and protein oxidation. However, treatment with melatonin was more effective in terms of reducing lipid peroxidation than pinoline, as the increases in MDA+4-HDA levels because of CCl(4) were reduced by 93.4% and 34.4% for melatonin or pinoline, respectively. Livers from CCl(4)-injected rats showed several histopathological alterations; above all, there were signs of necrosis and ballooning degeneration. The concurrent administration of melatonin or pinoline reduced the severity of these morphological changes. On the basis of the biochemical and histopathological findings, we conclude that both melatonin and pinoline were highly effective in protecting the liver against oxidative damage and membrane rigidity because of CCl(4). Therefore, these indoles may be useful as cotreatments for patients with hepatic intoxication induced by CCl(4).

:  Oxidative stress is involved in ischemia‐reperfusion injury and allograft rejection after transplantation. We studied two well‐known antioxidants, melatonin and ascorbic acid (AA), in relation to the survival of a pancreas transplantation model without immunosuppression. Forty‐eight Landrace pigs were divided into three groups (n = 16 each; eight donors and eight recipients) that received melatonin, AA, or no antioxidant therapy (controls). Melatonin and AA were administered (10 mg/kg body weight) intravenously to donors and recipients during surgery and on postoperative days 1–7. The molecules were also added (5 mm) to a University of Wisconsin preservation solution during organ cold storage. Melatonin significantly delayed acute rejection and prolonged allograft survival (25.1 ± 7.7 days) compared with the controls (8.1 ± 0.8 days, P = 0.013) and the AA group (9.4 ± 1.6 days, P = 0.049). Melatonin reduced indicators of oxidative stress, malondialdehyde, and 4‐hydroxyalkenals, in pancreatic samples collected during procurement, cold ischemia, and reperfusion. Melatonin also reduced serum pig‐major acute‐phase protein/inter‐α‐trypsin inhibitor heavy chain 4 (pMAP/ITIH4) in the early post‐transplantation period. AA only partially reduced oxidative damage 30 min postreperfusion and failed to prevent pMAP/ITIH4 elevations. These findings suggested that melatonin may be a useful therapeutic tool for organ transplantation.

No abstract

No abstract