Subacute toxicity of (-)15-deoxyspergualin in BALB/c mice. I. Hematological study.
(-)15-Deoxyspergualin (DSP), a bacterial metabolite obtained from Bacillus laterosporus, was shown to effectively suppress autoantibody production in mice and alloimmune reaction in mice and rats. Its potential toxicity and safety margin in BALB/c mice were studied by administering the drug, 0.5-5.0 mg/kg body weight, s.c., 6 days/week for 3 months. The animals were weighted every two weeks, and their blood was drawn for hematological and liver function studies. Control animals showed a gradual increase in body weight from 17.8 +/- 1.1 g (SD) to 20.2 +/- 3.2 g during the 3 months of treatment. The body weight of 0.5 mg- and 2.5 mg-DSP group was not significantly different from that of the control group. In contrast, 5.0 mg-DSP group of animals showed significant decrease in their weight compared with the control after 5 weeks of treatment (P less than 0.01). They were then sacrificed. WBC in 0.5 mg-, 2.5 mg- and 5.0 mg-DSP groups were significantly lower compared with the control after 3 months of treatment. On the other hand, only 5.0 mg-DSP group showed significantly lower level in their RBC, Hb and Hct values (P less than 0.05). In contrast, platelet counts in 2.5 mg- and 5.0 mg-DSP group significantly increased. No manifest effect due to DSP on differential count of leukocytes was observed, although on day 92, a significant difference was shown in the stab cells of the 0.5 mg-DSP group and in the eosinophils in the 2.5 mg-DSP.(ABSTRACT TRUNCATED AT 250 WORDS)
Okubo
M
M
Department of Medicine, Kitasato University School of Medicine, Kanagawa, Japan.
Masaki
Y
Y
Inoue
K
K
Hara
R
R
Taira
M
M
Kamata
K
K
Zhang
H M
HM
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000633:toxicity*; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D004906:Erythrocyte Count; D005260:Female; D006146:Guanidines / Q000097:blood / Q000633:toxicity*; D006400:Hematocrit; D006402:Hematologic Diseases / Q000139:chemically induced* / Q000503:physiopathology; D006454:Hemoglobins / Q000032:analysis; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D010976:Platelet Count
D000903:Antibiotics, Antineoplastic; D006146:Guanidines; D006454:Hemoglobins; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C037258:gusperimus