PROTECTIVE EFFECTS OF LAZAROID U74389G ON INTESTINAL GRAFT AFTER HETEROTOPIC SMALL-BOWEL TRANSPLANTATION IN RATS

Background. 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 blockin g effect of one of these substances (lazaroid U74389G) on lipid peroxi dation protects intestinal grafts morphologically and biologically in a heterotopic transplant model (SBT) in rats. Animals and methods. Het erotopic LEW were performed using Ringer lactate (4 degrees C) as pres ervation 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 und erwent only a laparotomy. Bacterial translocation (BT) was determined in mesenteric lymph nodes (MLN), liver (L), and spleen (S) 60 min afte r reperfusion, Tissue myeloperoxidase (MPO), malondialdehyde (MDA), an d percentage conversion xanthine dehydrogenase/xanthine oxidase (XD/XO ) were also determined in the ileal graft. Histological damage was gra ded according to Park's classification. Results. Tissue MDA (nmol/mg p rot) 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 sha m-operated group (0.40 +/- 0.05). Injury grades were also significantl y 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 wa s 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. Conclusio n. 21A U74389G inhibits lipid peroxidation, protects intestinal graft, and reduces BT after heterotopic SBT in rats, (C) 1998 Academic Press .