title: Comparison of intestinal cold preservation injury on pituitary adenylate cyclase-activating polypeptide in knockout and wild-type mice.
abstract: Tissue injury caused by cold preservation remains a problem in small intestinal transplantation. Pituitary adenylate cyclase-activating polypeptide (PACAP) has a central role in intestinal physiology. The objective of the present study was to compare the effects of cold ischemia injury in PACAP-38 knockout and wild-type mice after cold storage of small bowel. Cold ischemia was produced using small bowel preservation in University of Wisconsin solution at 4 degrees C in 20 PACAP-38 wild-type mice for 1, 3, and 6 hours (groups 1, 2, and 3, respectively) and 20 PACAP-38 knockout mice for 1, 3, and 6 hours (groups 4, 5, and 6, respectively). Biopsy samples of small bowel were obtained after laparotomy (control) and at the end of preservation periods. To determine oxidative stress, malondialdehyde, reduced glutathione, and superoxide dismutase concentrations were measured. Tissue damage was assessed using a quantitative method on sections stained with hematoxylin-eosin. After 6 hours, tissue lipid peroxidation was increased significantly in PACAP-38 knockout mice (mean +/- SD, 153.04 +/- 7.2 micromol/g) compared with sham-operated mice (110.44 +/- 5.5 micromol/g) and wild-type mice (120.0 +/- 1.1 micromol/g) (P < .05). The capacity and activity of the endogenous antioxidant system decreased significantly after 3 and 6 hours of preservation (reduced glutathione, 808.7 +/- 5.2 micromol/g and 720.4 +/- 8.7 micromol/g; and superoxide dismutase, 125.1 +/- 1.4 IU/g and 103.3 +/- 1.9 IU/g vs 212.11 +/- 5.8 IU/g; P < .05). Quantitative histologic analysis demonstrated destruction of mucosal and submucosal layers and crypts in knockout mice compared with wild-type mice. These processes depended on duration of cold preservation. These findings demonstrate that PACAP-38 has a key role in protection against intestinal cold preservation injury.
authors.affiliation: Department of Surgical Research and Techniques, University of Pécs Medical School, Pécs, Hungary. andrea.ferencz@aok.pte.hu
authors.forename: A
authors.initials: A
authors.lastname: Ferencz
authors.forename: K
authors.initials: K
authors.lastname: Nedvig
authors.forename: T
authors.initials: T
authors.lastname: Fekecs
authors.forename: B
authors.initials: B
authors.lastname: Rácz
authors.forename: G
authors.initials: G
authors.lastname: Wéber
authors.forename: H
authors.initials: H
authors.lastname: Hashimoto
authors.forename: A
authors.initials: A
authors.lastname: Baba
authors.forename: Z
authors.initials: Z
authors.lastname: Helyes
authors.forename: D
authors.initials: D
authors.lastname: Reglödi
mesh_terms: D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015925:Cryopreservation / Q000379:methods; D005978:Glutathione / Q000378:metabolism; D007328:Insulin; D007421:Intestine, Small / Q000378:metabolism; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009926:Organ Preservation / Q000379:methods; D019188:Organ Preservation Solutions; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D011887:Raffinose; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D007328:Insulin; D019188:Organ Preservation Solutions; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C055206:University of Wisconsin-lactobionate solution; D008315:Malondialdehyde; D000493:Allopurinol; D013482:Superoxide Dismutase; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose