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Subacute toxicity of (-)15-deoxyspergualin in BALB/c mice. II. Histopathological study
1Department of Medicine, Kitasato University School of Medicine, Kanagawa, Japan.
Abstract:
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)
Insights
Subacute toxicity of (-)15-deoxyspergualin (DSP) in mice caused significant histopathological changes in the spleen, bone marrow, and intestines, indicating immunosuppressive effects. DSP primarily impacted lymphoid and hematopoietic organs, with dose-dependent intestinal lesions observed.
Area of Science:
- Toxicology
- Immunology
- Histopathology
Background:
- Previous research focused on hematological effects of (-)15-deoxyspergualin (DSP).
- This study investigates the histopathological consequences of subacute DSP exposure.
Purpose of the Study:
- To elucidate the histopathological changes induced by subacute DSP administration in BALB/c mice.
- To assess the impact of DSP on organ weights and tissue morphology.
- To evaluate DSP's effect on lymphocyte surface markers.
Main Methods:
- BALB/c mice were administered DSP (0.5-5.0 mg/kg) for three months.
- Organ weights were measured, and tissues (heart, lungs, liver, spleen, kidneys, bone marrow, intestine) were processed for histopathological examination (HE, PAS staining).
- Avidin-biotin complex (ABC) technique was used to analyze splenic lymphocyte surface markers (Thy 1, B220).
Main Results:
- Significant reductions in heart, lung, liver, and spleen weights were observed in the 5 mg/kg DSP group.
- No abnormalities were noted in the heart, lungs, liver, or kidneys.
- Significant spleen and bone marrow changes, along with dose-dependent intestinal lesions (mucosal degeneration, inflammation, pseudo-membranes), occurred in the 5 mg/kg group.
- DSP treatment led to a preferential decrease in B cells in splenic corpuscles.
Conclusions:
- Histopathological alterations induced by DSP primarily affect lymphoid and hematopoietic organs.
- The observed changes suggest that DSP possesses immunosuppressive properties.
- Intestinal lesions indicate a broader toxicological profile for DSP beyond lymphoid tissues.