Antitumour activity and side effects of combined treatment with chitosan and cisplatin in sarcoma 180-bearing mice.
We examined the possible modulation by chitosan of the antitumour effects and side effects of cisplatin (cis-diaminedichloroplatinum, CDDP). The study showed that CDDP had potent antitumour activity when administered orally as well as intraperitoneally. We also compared the antitumour activity and side effects of orally administered CDDP plus orally administered chitosan versus intraperitoneally administered CDDP plus orally administered chitosan in sarcoma 180-bearing mice. When CDDP (1.25 mgkg(-1) x 2 day(-1)) was intraperitoneally administered to sarcoma 180-bearing mice, myelotoxicity (the reduction of leucocyte and platelet numbers), nephrotoxicity (the increase of blood nitrogen urea level), immunotoxicity (the reduction of spleen and thymus weight) and a reduction in body weight resulted. These intraperitoneally administered CDDP-induced side effects were not prevented by oral administration of chitosan (150 mgkg(-1) x 2 day(-1) and 750 mgkg(-1) x 2 day(-1)) for 14 consecutive days. On the other hand, the side effects such as the reductions of body and spleen weights induced by orally administered CDDP (1.25 mgkg(-1) x 2 day(-1)) were prevented by the oral administration of chitosan (150 mgkg(-1) x 2 day(-1) and 750 mg kg(-1) x 2 day(-1)). From these results, we conclude that the orally administered chitosan plus CDDP might be useful for the prevention of body weight reduction and immunotoxicity (the reduction of spleen weight) induced by the orally administered CDDP without diminishing antitumour activity.
Second Department of Medical Biochemistry, School of Medicine, Ehime University, Japan. yokim@m.ehime-u.ac.jp
Y
Y
Kimura
M
M
Onoyama
T
T
Sera
H
H
Okuda
D000284:Administration, Oral; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002614:Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects; D002686:Chitin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D048271:Chitosan; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D007263:Infusions, Parenteral; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012510:Sarcoma 180 / Q000188:drug therapy*
D002614:Chelating Agents; D002686:Chitin; D048271:Chitosan; D002945:Cisplatin