Bombesin and neurotensin reduce endotoxemia, intestinal oxidative stress, and apoptosis in experimental obstructive jaundice.
OBJECTIVE
To evaluate the effect of bombesin (BBS) and neurotensin (NT) on intestinal histopathology, intestinal oxidative stress, and endotoxemia in experimental obstructive jaundice.


BACKGROUND
Obstructive jaundice compromises gut barrier function, resulting in endotoxemia. BBS and NT, exerting various biologic actions on gastrointestinal tissues, preserve gut mucosal integrity in cases of injury or atrophy.


METHODS
Seventy male Wistar rats were randomly divided into 5 groups: I = controls, II = sham operated, III = bile duct ligation (BDL), IV = BDL + BBS (30 microg/kg/d), V = BDL + NT (300 microg/kg/d). By the end of the experiment, on day 10, endotoxin was measured in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically, and villus density, mucosal thickness, mitotic activity and apoptosis in crypts were assessed. In addition, ileal mucosa was analyzed for DNA and protein content. To estimate intestinal oxidant/antioxidant equilibrium, lipid peroxidation, protein oxidation, and thiol redox state (reduced glutathione [GSH], oxidized glutathione [GSSG], total nonprotein mixed disulfides [NPSSR], protein thiols [PSH], and protein disulfides [PSSP]) were determined on tissue homogenates from the terminal ileum.


RESULTS
BBS or NT administration significantly reduced portal and systemic endotoxemia observed in obstructive jaundice. Both factors reversed obstructive jaundice-induced morphologic features of intestinal atrophy, increasing villus density and mucosal thickness. This effect was accompanied by induction of mitoses and reduction of apoptosis in intestinal crypts. Mucosal DNA and protein content were reduced, although not to significant levels, in BDL animals and restored to control levels after BBS or NT treatment. Moreover, BBS or NT administration protected the intestine in jaundiced rats against oxidative stress, as demonstrated by reduction of intestinal lipid peroxidation, increase of the antioxidant GSH, and decrease of the oxidized forms GSSG and NPSSR, while BBS additionally reduced protein oxidation as well.


CONCLUSIONS
Administration of BBS or NT in bile duct-ligated rats exerts beneficial effects on intestinal oxidative stress, cell proliferation, apoptosis, and endotoxemia. This observation might be of potential value in patients with extrahepatic cholestasis.
Assimakopoulos
Stelios F
SF
Department of Internal Medicine, School of Medicine, University of Patras, Patras, Greece. sassim@upatras.gr
Scopa
Chrisoula D
CD
Zervoudakis
George
G
Mylonas
Panagiotis G
PG
Georgiou
Christos
C
Nikolopoulou
Vassiliki
V
Vagianos
Constantine E
CE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001839:Bombesin / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D019446:Endotoxemia / Q000473:pathology / Q000517:prevention & control*; D007422:Intestines / Q000187:drug effects / Q000503:physiopathology; D041781:Jaundice, Obstructive / Q000188:drug therapy / Q000503:physiopathology*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D023421:Models, Animal; D009479:Neuropeptides / Q000494:pharmacology; D009496:Neurotensin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism
D009479:Neuropeptides; D011506:Proteins; D013438:Sulfhydryl Compounds; D009496:Neurotensin; D001839:Bombesin