Triptolide prolonged allogeneic islet graft survival in chemically induced and spontaneously diabetic mice without impairment of islet function.
BACKGROUND
Triptolide (TPT) is a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook. F. It exhibits potent immunosuppressive and anti-inflammatory properties. This study was undertaken to investigate its effects on prolongation of islet allograft survival in rodents. Additionally, we investigated whether TPT would be toxic to islet function in vivo.


METHODS
We transplanted BALB/c islets to either chemically induced diabetic C57BL/6 mice or spontaneously diabetic nonobese diabetic (NOD) mice. TPT was injected within 2 weeks or continuously, until rejection, in the two combinations. Then, we evaluated the toxicity of TPT on islet function by daily injection to naive BALB/c or diabetic BALB/c that was cured by syngeneic islet transplantation under the kidney capsule. Mice injected with cyclosporine A (CsA) or vehicle served as controls. Intraperitoneal glucose tolerance tests (IPGTTs) performed at 4 and 8 weeks in the naive BALB/c group, and at 2, 4, 6, and 8 weeks in the syngeneic transplanted group.


RESULTS
The medium survival time of islets allograft from TPT treated C57BL/6 and NOD recipients were 28.5 days (range 24-30 days, n=10) and 33.0 days (range 15-47 days, n=6), respectively, and they were significantly different from those of the vehicle treated controls, which were 14.0 days (range 13-16 days, n=6) and 5.0 days (range 4-10 days, n=6), respectively (all P<0.0001). The IPGTT demonstrated that there was no difference between the TPT treated and vehicle treated groups, either in the normal or syngeneic transplanted islet BALB/c mice. However, CsA injection impaired islet function in both normal and syngeneic transplanted mice as early as 4 weeks.


CONCLUSIONS
TPT prolonged islets allograft survival in a chemically induced diabetic or an autoimmune diabetic murine model without impairment of islet function.
Xin
Ming-Jun
MJ
Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
Cui
Shi-Hua
SH
Liu
Shuang
S
Sun
Hai-Chen
HC
Li
Fei
F
Sun
Jia-Bang
JB
Luo
Bin
B
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000097:blood / Q000601:surgery*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery*; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology* / Q000633:toxicity; D004852:Epoxy Compounds / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D005951:Glucose Tolerance Test; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000633:toxicity; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010616:Phenanthrenes / Q000494:pharmacology* / Q000633:toxicity; D013997:Time Factors; D014184:Transplantation, Homologous; D015430:Weight Gain / Q000187:drug effects
D001786:Blood Glucose; D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D010616:Phenanthrenes; C001899:triptolide; D016572:Cyclosporine