Intraperitoneal injection of dextran sulfate as an anti-adherent drug for the prevention of peritoneal metastasis of cancer shows low toxicity in animals.
Intraperitoneal dextran sulfate with a mean molecular weight of 5 x 10(5) has been developed for use in an anti-adherent therapy against peritoneal carcinomatosis. The present study examined acute toxicity of i.p. injection of dextran sulfate in mice and rabbits. The 10, 50 and 90% lethal dose values are 0.213 (0.146-0.252), 0.336 (0.291-0.405) and 0.530 mg/g (0.431-0.873 mg/g: 95% confidence interval) in mice, respectively. These are markedly larger than the efficacious dose of 0.005-0.01 mg/g obtained previously. Death or symptoms of intoxication were seen within 3 days after administration of toxic doses. Rabbits received i.p. injection of dextran sulfate at 0.02 mg/g, which was close to the efficacious dose. At 2, 4, 6, 8 and 13 days after administration, blood was taken for biochemical and hematological analyses. Dextran sulfate at 0.02 mg/g induced no remarkable abnormal findings. These results suggest that the i.p. dextran sulfate is safe as an anti-adherent agent against peritoneal metastasis of cancer.
Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Japan.
A
A
Hagiwara
C
C
Sakakura
M
M
Shirasu
T
T
Togawa
Y
Y
Sonoyama
J
J
Fujiyama
Y
Y
Ebihara
T
T
Itoh
H
H
Yamagishi
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D016264:Dextran Sulfate / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007421:Intestine, Small / Q000187:drug effects; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control; D010534:Peritoneal Neoplasms / Q000517:prevention & control* / Q000556:secondary; D011817:Rabbits
D000970:Antineoplastic Agents; D016264:Dextran Sulfate