抗肿瘤血清胸腺因子9肽的急性毒性和遗传毒性

doi:10.3969/j.issn.1004-616x.2022.01.011

Abstract

Abstract: OBJECTIVE: To investigate acute toxicity and genotoxicity of an innovative antitumor drug -serum thymus factor 9 peptide. METHODS: Mice,rats,beagles were given 70.0 mg/kg by one-time injection to test for acute toxicity. Ames test,CHL test and micronucleus test were used to investigate genotoxicity. RESULTS: After treatments,the animals were in good spirits and behaved normally. There were no signs of excitation or inhibition. No acute toxicity was found. Ames test showed no significant increase in the number of mutant colonies at 1-5 000 μg/dish,similar to the solvent control group. CHL test showed no significant increase in chromosome aberration rate at 1 400-5 600 μg/mL (less than 3%),there was no statistical significance compared with the solvent control group (P>0.05). The micronucleus cell rates in the 17.5-70.0 mg/kg group were all less than 2.0‰,and there was no statistical significance compared with the solvent control group (1.2‰) (P>0.05). CONCLUSION: The maximum tolerated dose of serum thymic factor 9 peptide was greater than 70.0 mg/kg,which was 930 times of the recommended dosage for clinical patients. Acute toxicity and genotoxicity were not observed in the dose ranges for this investigation.

Key words: serum thymic factor 9 peptide, rats, mice, Beagles, acute toxicity, genotoxicity

CLC Number:

Q355

YANG Yu, HUANG Yali, LIN Fei, TANG Long. Acute toxicity and genotoxicity of antitumor serum thymic factor 9 peptide[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(1): 57-61.

References

[1] KOHDA Y, KAWAI Y, IWAMOTO N, et al. Serum thymic factor, FTS, attenuates cisplatin nephrotoxicity by suppressing cisplatin-induced ERK activation[J]. Biochem Pharmacol, 2005, 70(9):1408-1416.
[2] KOHDA Y, MATSUNAGA Y, YONOGI K, et al. Protective effect of serum thymic factor, FTS, on cephaloridine-induced nephrotoxicity in rats[J]. Biol Pharm Bull, 2005, 28(11):2087-2091.
[3] 张长平, 乐嘉静, 李湛君, 等. 血清胸腺因子(FTS)的抗肿瘤作用[J]. 药物分析杂志, 2007, 27(6):860-862.
[4] SEVERA M, ZHANG J, GIACOMINI E, et al. Thymosins in multiple sclerosis and its experimental models:moving from basic to clinical application[J]. Mult Scler Relat Disord, 2019, 27:52-60.
[5] 李湛军, 林飞, 范慧红, 等. 血清胸腺因子9肽对人结肠癌HT-29的抑瘤作用[J]. 癌变·畸变·突变, 2011, 23(5):374-376.
[6] 国家食品药品监督管理总局. 药物单次给药毒性研究技术指导原则[EB/OL]. (2014-05-13)[2021-05-06]. https://www.nmpa.gov.cn/xxgk/ggtg/qtggtg/20140513120001448.html.
[7] 国家食品药品监督管理总局. 药物遗传毒性研究技术指导原则[EB/OL]. (2018-03-15)[2021-05-06]. https://www.nmpa.gov.cn/directory/web/nmpa/xxgk/ggtg/qtggtg/20180315160901208.html.
[8] JUNG J A, NOH J H, JANG M S, et al. Safety evaluation of fermented Platycodon grandiflorus (Jacq.) A.DC. extract:genotoxicity, acute toxicity, and 13-week subchronic toxicity study in rats[J]. J Ethnopharmacol, 2021, 275:114138.
[9] CRISTINA DA COSTA ARALDI I, PIBER DE SOUZA T, DE SOUZA VENCATO M, et al. Preclinical safety assessment of the crude extract from Sida rhombifolia L. aerial parts in experimental models of acute and repeated-dose 28 days toxicity in rats[J]. Regul Toxicol Pharmacol, 2021, 124:104974.
[10] MERLINO P G, MARSH J A. The enhancement of avian NK cell cytotoxicity by thymulin is not mediated by the regulation of IFN-γ production[J]. Dev Comp Immunol, 2002, 26(1):103-110.
[11] YASUDA J, NISHIOKA W, SAKUDO A, et al. Suppressor mechanism of serum thymic factor on tumor necrosis factor-alpha-induced apoptosis in the mouse pancreatic beta-cell line[J]. Biochem Biophys Res Commun, 2003, 311(2):501-505.
[12] SAITOH N, AWAYA A, SAKUDO A, et al. Serum thymic factor prevents LPS-induced pancreatic cell damage in mice via up-regulation of bcl-2 expression in pancreas[J]. Microbiol Immunol, 2004, 48(9):629-638.
[13] LUNIN S M, NOVOSELOVA E G. Thymus hormones as prospective anti-inflammatory agents[J]. Expert Opin Ther Targets, 2010, 14(8):775-786.
[14] 郏建臣. 胸腺肽联合化疗对老年胃癌患者免疫功能及Th1、Th2细胞因子含量的影响[J]. 中国现代医学杂志, 2014, 24(36):51-54.
[15] 韩煦, 夏云龙. 抗肿瘤治疗相关的血管毒性[J]. 中国循环杂志, 2017, 32(7):716-718.
[16] 董超, 罗春香, 杨润祥. 抗肿瘤药物所致神经毒性防治的研究进展[J]. 重庆医学, 2018, 47(2):268-272.
[17] 孙星星, 闵大六. 抗肿瘤治疗所致心脏毒性的研究进展[J]. 中华诊断学电子杂志, 2019, 7(3):147-150.
[18] 陈素华, 刘红, 张艳华. 紫杉烷类抗肿瘤药物相关心血管毒性报告及文献分析[J]. 中国新药杂志, 2020, 29(20):2395-2400.

Acute toxicity and genotoxicity of antitumor serum thymic factor 9 peptide

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