Improved small intestinal preservation after lazaroid U74389G treatment and cold storage in University of Wisconsin solution.

The small intestine (SI) is highly sensitive to oxygen free radical-induced injury. The most common preservation solution, University of Wisconsin (UW) solution, does not adequately prevent free radical-induced injury. Lazaroids, and U74389G in particular, are a new class of compound that are potent inhibitors of superoxide-mediated lipid peroxidation. We studied the added influence of U74389G to 18-hr cold preservation of rat SI in UW solution. Three groups of rats were studied. In group 1, SI was excised and reperfused immediately. In group 2, SI was stored in UW solution at 4 degrees C for 18 hr. In group 3, U74389G was given to the SI graft before storage and again before reperfusion. Blood reperfusion of the grafts was achieved via connection to the superior mesenteric artery and portal vein of support rats. Functional recovery was assessed using a maltose tolerance test. Weight changes were calculated and histologic studies done. After 30 and 60 min of reperfusion, maltose uptake in group 3 was significantly better than that of the group 2, and returned to control levels. Significantly more tissue swelling was noted in group 3 over control, but the magnitude was less than that of group 2. Less transmural necrosis and villous blunting were noted in group 3 versus group 2; the appearance of the mucosa in group 3 approached that of group 1. We conclude that the use of U74389G treatment in addition to cold storage in UW solution improves recovery of graft function and minimizes morphologic damage to the small intestinal mucosa.

The cytopathology of metal overload.

Researchers have been able to demonstrate the cytotoxicity of copper overload in animal models. This has allowed them to not only localize the intracellular distribution of copper but also to study directly the subsequent organelle injury at the ultrastructural level. The lesions seen in copper overload appear to vary from species to species. In humans, marked mitochondrial abnormalities are seen in Wilson's disease while diet overloaded rats show nuclear destruction and various membranous abnormalities. Sequestration of copper within lysosomes appears to protect hepatocytes from its toxicity. However, the mechanism by which the metal is incorporated into lysosomes is not known.