Bombesin can rescue the enteric ganglia from FK506 neurotoxicity on small bowel transplantation.
OBJECTIVE
FK506 has been reported to have neurotoxic effects. The aim of this study was to investigate whether FK506 causes neurotoxic effects on the transplanted graft enteric ganglia (TGEG) and whether bombesin (BBS) can prevent such atrophy.


METHODS
Thirty rats heterotopically underwent small bowel transplantation and were divided into 5 groups as follows: group A, syngraft (SYN) alone; group B, SYN with FK506; group C, SYN with FK506 and BBS; group D allograft with FK506; group E, allograft with FK506 and BBS. From postoperative days 14 to 28, either BBS or normal saline was administered continuously. All recipients except for group A received FK506 daily. The ganglionic count was obtained by counting the number of protein gene product 9.5 immunohistochemically stained ganglia in the cross sections of each graft.


RESULTS
The number of TGEG in groups A, B, and C was 69.7 +/- 6.0, 51.5 +/- 7.7, and 84.8 +/- 10.2 ganglia per cross section, respectively. There was a significant difference between each group (P < .001). The number of TGEG in groups D and E was 44.6 +/- 7.5 and 65.1 +/- 9.5 ganglia per cross section, respectively. There was a significant difference between the 2 groups (P < .001).


CONCLUSIONS
FK506 causes severe neurotoxicity in transplanted grafts, and BBS protects graft enteric ganglia against the neurotoxic effects of FK506.
Higuchi
Koji
K
Division of Surgery, Children's Research Hospital, Kyoto Prefectural University of Medicine Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. higucci@koto.kpu-m.ac.jp
Kimura
Osamu
O
Furukawa
Taizo
T
Kinoshita
Hiromi
H
Iwai
Naomi
N
D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D005725:Ganglia, Autonomic / Q000187:drug effects* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007421:Intestine, Small / Q000187:drug effects* / Q000294:innervation / Q000473:pathology / Q000637:transplantation; D008286:Malabsorption Syndromes / Q000601:surgery; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000517:prevention & control; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D016377:Organ Transplantation; D051381:Rats; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000009:adverse effects*; D019737:Transplants
D007166:Immunosuppressive Agents; D018377:Neurotransmitter Agents; D001839:Bombesin; D016559:Tacrolimus