FK506 Induces the Atrophy of Enteric Ganglia in Small Bowel Transplantation, Which Can Be Prevented by the Neuropeptide Bombesin

Abstract

Purpose FK506, which is widely used for immunosuppression, is reported to have neurotoxicity. However, its neurotoxicity for transplanted graft enteric ganglia (TGEG) has never been reported. The aim of this study was to investigate whether FK506 has a neurotoxic effect on TGEG, and whether bombesin (BBS) prevents such atrophy. Methods Eighteen rats that underwent syngertic heterotopic small bowel transplantation (SBTx) using a cuff method were divided into three groups of six rats each; A: SBTx alone, B: SBTx with FK506, C: SBTx with FK506/BBS. Either BBS (10 mg/kg/d) or normal saline was infused continuously from day 14 to 28. Rats in groups B and C were administered FK506 (0.32 mg/kg/day, intramuscularly) daily. Analysis of TGEG was performed using immunohistochemistry with protein gene product (PGP) 9.5. The ganglionic number was obtained by counting PGP9.5-positive ganglia in each graft. Results The number of TGEG were reduced significantly in group B (51.5 ± 7.7 ganglia per cross section (G/CS)) compared with group A (69.7 ± 6.0 G/CS), but were well preserved in group C (84.8 ± 10.2 G/CS). There were significant differences between groups B and C ( P < .001) and also between groups A and C ( P < .001). Conclusion FK506 showed severe neurotoxicity on transplanted grafts, and bombesin could rescue TGEG against FK506 neurotoxicity.