Beneficial effect of muroctasin on experimental leukopenia induced by cyclophosphamide or irradiation in mice.
Subcutaneous injection of N2-[N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a synthetic muramyl dipeptide derivative, favoured recovery of mice from experimental leukopenia induced by cyclophosphamide or by irradiation with X-rays. These effects were observed only when MDP-Lys(L18) treatment occurred after cyclophosphamide injection or X-ray irradiation. Prophylactic treatment resulted in neither preventive nor restorative efficacy on leukopenia. In contrast, glutathione was hardly effective on leukopenia in both models, irrespective of treatment timing. The restorative efficacy of muroctasin was found to be dose-dependent and to be attributable at least to its augmenting effect on colony-stimulating factor production, followed by the marked proliferation and differentiation of myeloblasts towards mature granulocytes in the bone marrow. These beneficial effects of MDP-Lys(L18) warrant further evaluation of its clinical usefulness.
Nakajima
R
R
Research Institute, Daiichi Seiyaku Co., Ltd., Tokyo, Japan.
Ishida
Y
Y
Yamaguchi
F
F
Otani
T
T
Ono
Y
Y
Nomura
M
M
Une
T
T
Osada
Y
Y
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division; D055598:Chemical Phenomena; D002621:Chemistry; D003115:Colony-Stimulating Factors / Q000097:blood; D003520:Cyclophosphamide / Q000633:toxicity; D005978:Glutathione / Q000627:therapeutic use; D006410:Hematopoiesis; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects / Q000528:radiation effects; D007970:Leukopenia / Q000209:etiology / Q000517:prevention & control / Q000628:therapy*; D008297:Male; D051379:Mice; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000628:therapy; D013154:Spleen / Q000473:pathology
D000276:Adjuvants, Immunologic; D003115:Colony-Stimulating Factors; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D003520:Cyclophosphamide; D005978:Glutathione; C036866:romurtide