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[Observation of pathological morphology on nervous system of rat with maximum dose sophoridine in chronic toxic test]
Xue-Mei Li1, Wen-Hua Zhuang, Zhi-Zi Jiang
1Department Pathology, Jiangxi Traditional Chinese Medicine Institute, Nanchang, Jiangxi,330006, P.R.China.
Background & Objective:
Sophoridine is a new anticancer drug with noticeable antitumor action and lower toxicity. No marked influence on bone marrow was found till now. The main toxicity is presented in nervous system. This study was to observe the morphological changes of the nervous system of the rats, which were treated with maximum dose of sorphoridine for a long time.
Methods:
30 rats,half of male when and half of female, were randomly divided into experimental group and control group. In the experimental group,rats were treated with maximum dose of sorphoridine [32 mg x(kg x d)(-1) ip, qd] for 60 days. In control group, rats were treated with the same volume of saline everyday for 60 days. The rats in both groups were killed at 20 d, 40 d, 60 d, and 75 d, respectively. The brain and spinal cord were taken out and made into pathological slices, which were stained by HE stain and special stain, sach as Nissel's body stain, glial fibrillary stain and myelin sheath stain. The differences in morphology between the two groups was observed.
Results:
No pathological change was found in rats' cerebral cortex,internal capsul, striated body, hippocampus, substantia nigra,and spinal cord when the rats' were treated with sophoridine 32 mg x(kg x d)(-1) ip for 20 d, 40 d, 60 d. In the rats who had presented nervous system syndrome repeatedly or died for convulsion, or the rats who were killed in convalescence period (15 d after final administration), there was no pathological change either.
Conclusion:
No pathological changes and delayed changes in the nervous tissues were found when the rats were given maximum dose of Sophoridine continuously for 60 d. Our study showed that the syndrome of nervous system caused by Sophoridine is functional and stimulational, and can be recovered,and there is no any delayed change and sequela.
Insights
Sophoridine, an anticancer drug, showed no nervous system damage in rats even at maximum doses for 60 days. Observed nervous system effects were functional and reversible, indicating no lasting damage.
Area of Science:
- Pharmacology
- Neuroscience
- Oncology
Background:
- Sophoridine is a novel anticancer agent with demonstrated antitumor activity and reduced toxicity.
- Primary toxicity concerns with Sophoridine are neurological, not hematological.
- This study investigates the long-term neurological effects of Sophoridine in a rat model.
Purpose of the Study:
- To evaluate morphological changes in the rat nervous system following prolonged administration of the maximum Sophoridine dose.
- To determine if Sophoridine induces any pathological or delayed neurological sequelae.
Main Methods:
- 30 rats (male/female) were divided into experimental (Sophoridine, 32 mg/kg/day) and control (saline) groups.
- Animals were administered daily intraperitoneal injections for 60 days.
- Nervous tissues (brain, spinal cord) were collected at multiple time points and analyzed using HE and special stains.
Main Results:
- No significant pathological alterations were observed in various brain regions or the spinal cord during or after Sophoridine treatment.
- Even in rats exhibiting neurological symptoms or those in the recovery phase, no pathological changes were detected.
- Histological examination revealed no Sophoridine-induced damage to neural tissues.
Conclusions:
- Continuous administration of the maximum Sophoridine dose for 60 days did not result in pathological changes in the nervous system.
- Neurological syndromes associated with Sophoridine appear to be functional and reversible.
- The study indicates Sophoridine lacks delayed neurological toxicity or permanent sequelae.
