PG490-88, a new immunosuppressant, effectively prevents acute and chronic rejection in rat renal allografts.
PG490-88 is a semisynthetic derivative of the novel compound PG490 (triptolide) purified from a Chinese herb. It has been shown to prolong acute allograft survival in multiple experimental organ transplant models. However, the effect of PG490-88 on prevention of acute and chronic renal allograft rejection has not been determined. Kidneys of ACI or F344 rats were transplanted into bilaterally nephrectomized LEW recipients as the acute or chronic allograft rejection models, respectively. Treatment of LEW recipients with PG490-88 significantly prolonged ACI kidney graft survival in a dose-dependent manner when compared with the untreated allograft controls. LEW recipients of F344 kidney grafts who received PG490-88 for 90 days with a brief course of low-dose FK506 showed normal serum creatinine levels and markedly reduced histological changes of chronic rejection at day 90 after transplantation. These results suggest that PG490-88 significantly prolongs kidney allograft survival in an acute rejection model and prevents chronic allograft rejection in rats.
Pan
F
F
Basic Research, Evanston Northwesetern Healthcare, Northwestern University, Evanston, Illinois 60201, USA.
Fisniku
O
O
Wynn
C
C
Erickson
L M
LM
Crews
G
G
Jang
M S
MS
Sudo
Y
Y
Tamura
K
K
Kobayashi
M
M
Benediktsson
H
H
Jiang
H
H
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D004224:Diterpenes / Q000627:therapeutic use*; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology
D004224:Diterpenes; D007166:Immunosuppressive Agents; C417603:omtriptolide