Beneficial effects of growth hormone and insulin-like growth factor I on intestinal bacterial translocation, endotoxemia, and apoptosis in experimentally jaundiced rats

Background: This study was undertaken to investigate the effect of growth h ormone (GH) and insulin-like growth factor I (IGF-I), two well-known growth factors, on bacterial translocation, endotoxemia, enterocyte apoptosis, an d intestinal and liver histology in a model of experimental obstructive jau ndice in rats. Study Design: One hundred six male Wistar rats were divided into five group s: I (n = 21), controls; II (n = 22), sham operated; III (n = 22), bile duc t ligation (BDL); IV (n = 21), BDL and GH treatment; and V (n = 20), BDL an d IGF-I administration. By the end of the experiment, on day 10, blood bili rubin was determined, and mesenteric lymph nodes, liver specimens, and bile from the bile duct stump were cultured. Endotoxin was measured in portal a nd aortic blood. Tissue samples from the terminal ileum and liver were exam ined histologically and apoptotic body count (ABC) in intestinal mucosa was evaluated. Mucosal DNA and protein content were also determined. Results: Bilirubin increased significantly after BDL (p < 0.001). Bile from the bile duct was sterile. In group III, MLN and liver specimens were cont aminated by gut origin bacteria (significant versus group I and II, p < 0.0 01, respectively). GH reduced significantly positive cultures (p < 0.01), a nd IGF-I had no effect. BDL resulted in significant increase in portal and aortic endotoxemia (p < 0.001); treatment with GH and IGF-I reduced it (p < 0.001).. Mucosal DNA and protein content were reduced in animals with BDL and after treatment with GH or IGF-I; an increase to almost normal levels w as noted in DNA, but not in protein. Overall the ileal architecture remaine d intact in all animal groups. The ABC increased after BDL. After GH and IG F-I administration, the ABC decreased significantly, and there was no diffe rence between GH and IGF-I treated animals. After BDL, liver biopsies displ ayed typical changes of biliary obstruction, which were significantly impro ved after administration of GH and IGF-I. Conclusions: Treatment with GH and IGF-I in rats with experimental obstruct ive jaundice reduces endotoxemia, and it improves liver histology. Apoptosi s, in the intestinal epithelium, may serve as a morphologic marker of the i leal mucosal integrity, demonstrating the proliferative potential of GH and IGF-I in cases of obstructive jaundice, and this might be of potential val ue in patients with such conditions. (J Am Coll Surg 2000;190:423-431. (C) 2000 by the American College of Surgeons).