Subacute toxicity of (-)15-deoxyspergualin in BALB/c mice. II. Histopathological study.
Following the preceding report on hematological aspects in subacute toxicity of (-)15-deoxyspergualin (DSP), the present report dealt with the histopathological changes produced by DSP, 0.5-5.0 mg/kg, given to BALB/c mice for three months. At sacrifice, various internal organs such as heart, lungs, liver, spleen and kidneys, were taken, and their wet weights immediately measured. HE- or PAS-stained sections were histopathologically studied under light microscope. Additionally, frozen sections of the spleen were prepared to evaluate the effect of DSP on the lymphocyte surface markers like thy 1 and B220 by avidin-biotin complex (ABC) technique. Although the mean weights of lungs, liver, spleen and kidneys in the 0.5 mg- and 2.5 mg-DSP groups were not significantly different from those in the control animals, the weights of the heart, lungs, liver and spleen in the 5 mg-DSP group were significantly lower. Histopathological studies by light microscopy revealed no abnormalities in the heart, lungs, liver or kidneys taken from the mice given 0.5-5.0 mg/kg DSP. In contrast, significant changes were observed in the spleen and bone marrow of the 5.0 mg group of mice. Likewise, in the intestine of the 0.5-5.0 mg groups dose-dependent lesions, such as degeneration or disappearance of the mucosal epithelium, infiltration by inflammatory cells, and pseudo-membrane formation, was observed. By ABC technique, preferential decrease of B cells was seen in the splenic corpuscles of the DSP-treated mice. Histopathological changes due to DSP predominantly seen in the lymphoid and/or hematopoietic organs may be directly related to the immunosuppressive potency inherent to this drug.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhang
H M
HM
Department of Medicine, Kitasato University School of Medicine, Kanagawa, Japan.
Inoue
K
K
Masaki
Y
Y
Hara
R
R
Kamata
K
K
Okubo
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000633:toxicity*; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D006146:Guanidines / Q000097:blood / Q000633:toxicity*; D007150:Immunohistochemistry; D007422:Intestines / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D006146:Guanidines; C037258:gusperimus