CN-122005543-A - Animal model building method for testicular toxicity

Abstract

The invention belongs to the field of basic medical research, and particularly relates to an animal model establishing method for testicular toxicity, which comprises the following steps of carrying out intragastric administration of a preparation containing podophyllotoxin to a male rat at a dosage of 15 mg per kg of body weight per day and continuously carrying out the administration for 4 days, wherein the method can induce the rat to generate a testicular toxicity phenotype, and the phenotype at least comprises the obvious reduction of the number and the decline of the vitality of sperms, the abnormal rise of the testosterone level in serum, and the irregular morphology of seminiferous tubules and the thinning of seminiferous epithelium of testicular tissues.

Inventors

• LIU CHUANXIN
• Shao yuanyang
• WANG XUE
• DUAN JIAJIA

Assignees

• 河南科技大学第一附属医院

Dates

Publication Date

20260512

Application Date

20260313

Claims (10)

1. 1. A method for establishing an animal model of testicular toxicity is characterized by comprising the steps of carrying out intragastric administration of a preparation containing podophyllotoxin to male rats at a daily dosage of 15 mg/kg body weight, and continuously carrying out the administration for 4 days, wherein the method can induce the rats to generate a testicular toxicity phenotype, and the phenotype at least comprises the steps of obviously reduced number and activity of sperms, abnormally increased serum testosterone level and irregular seminiferous tubule morphology and thinning of seminiferous epithelium of testicular tissues.
2. 2. The method of animal modeling of testosterone toxicity of claim 1, wherein said testosterone phenotype further comprises a significant increase in sperm cell rate and a significant decrease in sperm cell survival rate.
3. 3. The method of animal modeling of testosterone toxicity according to claim 1 or 2, wherein said testosterone phenotype further comprises a significant reduction in serum follicle stimulating estrogen levels.
4. 4. The method of animal modeling of testicular toxicity according to claim 1, wherein the testicular toxicity phenotype further comprises a significant decrease in the index of testicular viscera.
5. 5. The method of animal modeling of testicular toxicity according to claim 1, wherein the male rats are SPF grade SD rats of 12 weeks of age.
6. 6. A method for modeling testicular toxicity according to claim 1, wherein the preparation comprising podophyllotoxin is a suspension of podophyllotoxin dissolved in 2% by volume of dimethyl sulfoxide and then fixed to a volume with a sodium carboxymethyl cellulose solution having a mass concentration of 0.5%.
7. 7. An animal model of testicular toxicity established by the method of any one of claims 1 to 6.
8. 8. Use of the animal model of testosterone toxicity of claim 7 for screening or evaluating reproductive toxicity.
9. 9. Use of the animal model of testosterone of claim 7 for studying the mechanism of male reproductive system injury caused by podophyllotoxin.
10. 10. Use of the animal model of testicular toxicity according to claim 7 for the development or alleviation of a drug or health care product of reproductive toxicity.

Description

Animal model building method for testicular toxicity Technical Field The invention relates to the technical field of animal models for basic scientific research, in particular to an animal model building method for testicular toxicity. Background Podophyllotoxin (podophyllotoxin), chemical name 5R-5,8,8 alpha, 9-tetrahydro-9-hydroxy-5- (3, 4, 5-trimethoxyphenyl) furan (3 ',4':6, 7) naphtho- [2,3-d ] -1, 3-dioxol-6 (5 aH) -one, is an extremely widely distributed natural lignan compound, and is found in plants of Podophyllum, folium Nelumbinis, and Podophyllum in berberidaceae. The podophyllotoxin and analogues thereof have the activities of resisting tumors, resisting viruses, inhibiting bacteria and the like, wherein the antitumor effect is most remarkable, and the chemical semisynthetic derivatives etoposide and teniposide of the podophyllotoxin are applied to the clinical treatment of various tumors at present, so that good effects are obtained, and the clinical value is outstanding. However, podophyllotoxin is limited by its own toxicity and cannot be used in clinic directly. At present, a plurality of cases of poisoning and even death after taking podophyllotoxin have been clinically reported, the probability of success of rescue is smaller, different poisoning degrees show different symptoms, the main symptoms of mild poisoning include nausea, vomiting, diarrhea and severe failure and collapse, neurotoxicity effect can be generated, and severe poisoning can cause injury of tissue viscera or toxic shock and even death. The nervous system reaction occurs later and lasts longer, and can be manifested as convulsions, deep coma, paralysis of breath and the like, and the cerebral poisoning can be manifested as dermatitis cutaneus. Pathological results show that liver function, kidney function and heart function are impaired to varying degrees after poisoning. The prior patent (CN 120022267B) discloses the application of the podophyllotoxin to the induction of acute lung injury, and the podophyllotoxin can be used for inducing and establishing an animal model of the acute lung injury for clinical research on toxic reaction of the podophyllotoxin. However, the specific toxicity of podophyllotoxins on the male reproductive system, particularly the systemic effects on testicular tissue, spermatogenesis and endocrine hormones of reproduction, is currently lacking in stable, reproducible animal models for standardized studies. Disclosure of Invention The invention aims at providing a method for establishing an animal model of testicular toxicity, which is used for determining the specific toxicity of podophyllotoxin to a male reproductive system and providing a stable and repeatable animal model. In order to solve the technical problems, the animal model establishment method of testicular toxicity provided by the invention is realized by the following steps: A method for establishing an animal model of testicular toxicity comprises the steps of administering a preparation containing podophyllotoxin to male rats by lavage at a daily dose of 15mg/kg body weight for 4 days, wherein the method is capable of inducing the rats to generate a testicular toxicity phenotype which at least comprises a significant reduction in sperm count and reduced motility, abnormally elevated serum testosterone levels, and irregular seminiferous tubule morphology and thinning of seminiferous epithelium of testicular tissues. Optionally, the testosterone phenotype further comprises a significant increase in sperm abnormality rate and a significant decrease in sperm survival rate. Optionally, the testosterone phenotype further comprises a significant reduction in serum follicle stimulating estrogen levels. Optionally, the testicular toxicity phenotype further comprises a significant decrease in the index of testicular viscera. Alternatively, the male rats are SPF grade SD rats of 12 weeks of age. Optionally, the preparation containing the podophyllotoxin is a suspension prepared by dissolving the podophyllotoxin in dimethyl sulfoxide with the volume concentration of 2%, and then fixing the volume of a sodium carboxymethyl cellulose solution with the mass concentration of 0.5%. An animal model of testicular toxicity established by the method of any one of claims 1 to 6. The invention also provides application of the testicular toxicity animal model in screening or evaluating reproduction toxicity. The invention also provides application of the testicular toxicity animal model in researching a male reproductive system injury mechanism caused by podophyllotoxin. The animal model establishment method for testicular toxicity provided by the invention determines the specific toxicity of podophyllotoxin to the male reproductive system and provides a stable and repeatable animal model. The testicular toxicity model of the rat obtained by the modeling method provided by the invention has the advantages that the testosterone level is obviously increa