Administration of nitric oxide with caspase inhibitors minimizes bacterial translocation in experimental intestinal transplantation.
BACKGROUND
Bacterial translocation (BT) has been suggested to be responsible for the high incidence of infections occurring after small-bowel transplantation (Trp). Nitric oxide (NO) and apoptosis could affect cell demise. The aim of this study was to asses whether supplementation of University of Wisconsin (UW) solution with NO donors and apoptosis inhibitors can abolish BT in Trp.


METHODS
The following experimental groups were studied: sham, Trp, intestinal transplantation, Trp+spermine NONOate (NONOs), and Trp+NONOs+caspase inhibitor Z-Val-Ala-Asp(Ome)-fluoromethylketone(Z-VAD-fmk). Histologic analysis, caspase-3 activity, DNA fragmentation, and BT from graft to mesenteric lymph nodes, liver, and spleen were measured in tissue samples after transplantation.


RESULTS
During intestinal transplantation, apoptosis and necrosis were increased, showing graft injury and high levels of BT. The rats treated with NONOs showed a histologic protection of transplanted graft and a decrease in BT despite caspase-3 and DNA fragmentation-inducing effects. Administration of caspase inhibitor Z-VAD to NONOs-treated rats reversed the NO apoptosis-inducing effects and showed the lowest levels of BT in all tissues.


CONCLUSIONS
Exogenous administration of NO associated with the inhibition of apoptosis maintains the graft in optimal conditions in terms of BT and improves the histology of the graft after intestinal transplantation in rats.
Azuara
Daniel
D
Department of Surgery and Surgical Specialities, University of Barcelona School of Medicine-Campus Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
Sola
Anna
A
Hotter
Georgina
G
Calatayud
Laura
L
Jaurrieta
Eduardo
E
de Oca
Javier
J
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018988:Bacterial Translocation / Q000187:drug effects*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D005978:Glutathione; D007328:Insulin; D007422:Intestines / Q000637:transplantation*; D023421:Models, Animal; D009569:Nitric Oxide / Q000627:therapeutic use*; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D009589:Nitrogen Oxides; D019188:Organ Preservation Solutions; D011887:Raffinose; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D013096:Spermine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014184:Transplantation, Homologous / Q000009:adverse effects; D014364:Tryptophan / Q000627:therapeutic use
D061945:Caspase Inhibitors; D007328:Insulin; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D019188:Organ Preservation Solutions; D015842:Serine Proteinase Inhibitors; C055206:University of Wisconsin-lactobionate solution; C091861:spermine nitric oxide complex; D013096:Spermine; D009569:Nitric Oxide; D000493:Allopurinol; D014364:Tryptophan; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose