Subacute toxicity of (-)15-deoxyspergualin in BALB/c mice. I. Hematological study.

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Abstract
(-)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 weighed every two weeks, and their blood was drawn for hematological and liver function studies. Control animals showed a gradual increace 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<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<0.05). In contrast, platelet counts in 2.5 mg- and 5.0 mg-DSP groups 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. SGOT level following 5.0 mg-DSP treatment for 5 weeks was significantly elevated compared with the pre-treatment level (P<0.05). The present study shows that the safety limit of long-term treatment with DSP may be 2.5 mg/kg body weight or less and that DSP preferentially affects lymphoid organs, although higher dose of DSP may also be toxic to the bone marrow system.

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