Protective effects of lazaroid U74389G on intestinal graft after heterotopic small bowel transplantation in rats

Experimental studies have shown that 21-aminosteroids (21-A) are powerful inhibitors of superoxide-mediated iron-dependent lipid peroxidation. This study was aimed at determining how far the blocking effect of one of these substances (lazaroid U74389G) on lipid peroxidation protects intestinal grafts morphologically and biologically in a heterotopic transplant model (SBT) in rats.

Heterotopic LEW were performed using Ringer lactate (4 degrees C) as preservation solution. In Group 1 (n = 7) the donor and recipient animals received 3 and 6 mg/kg of the 21-A U74389G, respectively. Group 2 (n = 7) received the same doses of the vehicle of the drug. Sham group underwent only a laparotomy. Bacterial translocation (BT) was determined in mesenteric lymph nodes (MLN), liver (L), and spleen (S) 60 min after reperfusion. Tissue myeloperoxidase (MPO), malondialdehyde (MDA), and percentage conversion xanthine dehydrogenase/xanthine oxidase (XD/XO) were also determined in the ileal graft. Histological damage was graded according to Park's classification.

Tissue MDA (nmol/mg prot) was significantly lower in Group 1 (0.53 +/- 0.09) than in Group 2 (3.66 +/- 1, P < 0.05) and showed levels similar to those of the sham-operated group (0.40 +/- 0.05). Injury grades were also significantly different in both study groups (Group 1, 0-1; Group 2, 2-3, P < 0.05). BT (log CFU/g tissue) in Group 1 were MLN, 0; L, 0.36; and S, 0. In Group 2, MLN, 1.07; L, 0.81; and S, 1.49 (P < 0.05 in MLN). Increase in MPO activity (U/g prot) in comparison with sham-operated animals was similar in the two study groups (Group 1, 1.49 +/- 0.58; Group 2, 1.22 +/- 0.46; Sham, 0.34 +/- 0.37 (P < 0.05 1,2 vs sham). Conversion of XD to XO was unaffected by the supplementation of the drug.

21A U74389G inhibits lipid peroxidation, protects intestinal graft, and reduces BT after heterotopic SBT in rats.