盐酸苯海拉明咖啡因复方的遗传毒性评价

doi:10.3969/j.issn.1004-616x.2022.02.014

Abstract

Abstract: OBJECTIVE： To investigate genetic toxicity of diphenhydramine hydrochloride and caffeine (mass ratio of diphenhydramine/caffeine is 1/2.4). METHODS：Ames test，chromosomal aberration test in CHL cells and ICR mouse bone marrow micronucleus assay were used to evaluate dphenhydramine hydrochloride and caffeine compound. In Ames test， TA97， TA98， TA100， TA102 and TA1535 were selected as indicator strains，and five test dose groups of 0.5，5，50，500 and 5 000 mg/dish were set. Chromosomal aberration test of CHL cells was divided into three dose groups，low dose (8.45 mg/mL)，medium dose (16.9 mg/mL) and high dose (33.8 mg/mL). Mouse bone marrow micronucleus assay：ICR mice were given the compounds by oral gavage. There were three dose groups：low dose (21.59 mg/kg)，medium dose (43.17 mg/kg) and high dose (86.35 mg/kg). RESULTS：Results of the Ames test show that there was no mutagenicity against Salmonella typhimurium with or without the metabolic activation system (S9). After CHL cells were exposed for 24 h and 4 h with or without S9， no chromosomal aberration effect was observed. In the mouse bone marrow micronucleus assay，the induction rates of micronucleus for the three doses were not significantly different from that of the solvent control group (P>0.05). CONCLUSION： These results indicate that diphenhydramine hydrochloride and caffeine compound had no genotoxicity based on our experimental conditions.

Key words: diphenhydramine, caffeine, genetic toxicity, Ames test, chromosomal aberration test, micronucleus assay

CLC Number:

Q355

SHI Wenjing, ZHANG Jiqianzhu, ZHU Jiangbo, ZHANG Xiaofang, WANG Ruina, DAI Xiaoyu, REN Lijun, TIAN Yijun. Evaluation of genotoxicity of diphenhydramine hydrochloride and caffeine compound[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(2): 149-153,157.

References

[1] 孙兴和. 晕动病[J]. 辽宁医学杂志, 1992, 2: 63-65.
[2] 李佑昶, 马婵娟, 姚晓东, 等. 晕动病的预防和治疗进展[J]. 河北医药, 2020, 42(16): 2513-2516, 2521.
[3] 骆惠婷. 苯海拉明联合盐酸氟桂利嗪及山莨菪碱治疗周围性眩晕的疗效[J]. 数理医药学杂志, 2020, 33(3): 438-439.
[4] 傅伟强, 谭志雄. 碳酸氢钠联合苯海拉明治疗眩晕症疗效观察[J]. 吉林医学, 2015, 36(12): 2591-2592.
[5] 易超然, 卫中庆. 咖啡因的药理作用和应用[J]. 医学研究生学报, 2005, 18(3): 270-272.
[6] CRAWFORD C, TEO L, LAFFERTY L, et al. Caffeine to optimize cognitive function for military mission-readiness: a systematic review and recommendations for the field[J]. Nutr Rev, 2017, 75(Sup 2): 17-35.
[7] 王红霞, 李雪, 丁平田. 苯海拉明口腔溶解膜的制备及溶出度测定[J]. 中国药剂学杂志, 2020, 18(3): 135-146.
[8] RADOVANOVIC D, MEIER P J, GUIRGUIS M, et al. Dose-dependent toxicity of diphenhydramine overdose[J]. Hum Exp Toxicol, 2000, 19(9): 489-495.
[9] 杨春永. 苯海拉明中毒二例报告[J]. 北京医学, 2003, 25(6): 406.
[10] 周玉林, 杨建学, 李岩, 等. 口服苯海拉明急性中毒死亡1例[J]. 法医学杂志, 2007, 23(2): 152-153.
[11] MUSGRAVE I F, FARRINGTON R L, HOBAN C, et al. Caffeine toxicity in forensic practice: possible effects and under-appreciated sources[J]. Forensic Sci Med Pathol, 2016, 12(3): 299-303.
[12] WILLSON C. The clinical toxicology of caffeine: a review and case study[J]. Toxicol Rep, 2018, 5: 1140-1152.
[13] 上官珠, 连其深, 杨敬格, 等. 蛇床子总香豆素对中枢神经系统的抑制作用[J]. 赣南医学院学报, 1992, 12(1): 10-13.
[14] 潘晓靓, 汪晖, 陈曼, 等. 咖啡因暴露对小鼠胚胎发育的影响及机制[J]. 毒理学杂志, 2007, 21(4): 334.642.
[15] 国家药典委员会. 中华人民共和国药典[S]. 二部. 北京: 中国医药科技出版社, 2015.
[16] 国家食品药品监督管理局.【ZH】GPT2-1药物遗传毒性研究技术指导原则[S]. 北京: 中国标准出版社, 2018: 3-17.
[17] 周海钧. 药品注册的国际技术要求: 安全性部分[M]. 北京: 人民卫生出版社, 2007: S3A.
[18] OECD. Test No. 471: Bacterial Reverse Mutation Test[EB/OL]. (2020-06-29) [2021-04-26]. https://www.oecd-ilibrary.org/docserver/9789264071247-en.pdf?expires=1638934969&id=id&accname=guest&checksum=B94C9686FE1F48AE6BA251A1C2609055.
[19] OECD. Test No. 474: Mammalian Erythrocyte Micronucleus Test [EB/OL]. (2016-06-29) [2021-04-26]. https://www.oecd-ilibrary.org/docserver/9789264264762-en.pdf?expires=1638936708&=id&accname=guest&checksum=58C28BDE9FBAF97D0BDD4E5B53EEDADE.
[20] OECD. Test No. 473: In Vitro Mammalian Chromosome Aberration Test[EB/OL]. (2016-06-29) [2021-04-26]. https://www.oecd-ilibrary.org/docserver/9789264264649-en.pdf?expires=1638936881&id=id&accname=guest&checksum=5A036B5CB 6C90919A4DC7DFE35BCA3EB.
[21] 王亚楠, 文海若, 王雪. 遗传毒性基因突变评价方法的研究进展[J]. 癌变·畸变·突变, 2019, 31(5): 406-411.
[22] 欧红梅, 周长慧, 涂宏刚, 等. 流式细胞术检测体外微核方法的建立[J]. 癌变·畸变·突变, 2015, 27(1): 39-43.
[23] 韩天娇, 周长慧, 常艳. 体内碱性彗星试验与微核试验联合测定甲磺酸乙酯遗传毒性方法的建立[J]. 癌变·畸变·突变, 2016, 28(4): 277-280.
[24] 周长慧, 韩天娇, 黄鹏程, 等. 大鼠多器官彗星试验方法的验证研究[J]. 癌变·畸变·突变, 2020, 32(3): 233-237.
[25] 陈高峰, 王亚楠, 王丹, 等. Pig-a基因突变试验研究进展[J]. 癌变·畸变·突变, 2019, 31(6): 492-497.
[26] ANDREWS A W, LIJINSKY W, SNYDER S W. Mutagenicity of amine drugs and their products of nitrosation[J]. Mutat Res Toxicol, 1984, 135(2): 105-108.
[27] LOVEDAY K S, LUGO M H, RESNICK M A, et al. Chromosome aberration and sister chromatid exchange tests in Chinese hamster ovary cells in vitro: II. Results with 20 chemicals[J]. Environ Mol Mutagen, 1989, 13(1): 60-94.
[28] Chemical Book[EB/OL]. [2021-04-26]. https://www.chemicalbook.com/ProductChemicalPropertiesCB0202769_EN.htm.
[29] NEHLIG A, DEBRY G. Potential genotoxic, mutagenic and antimutagenic effects of coffee: a review[J]. Mutat Res, 1994, 317(2): 145-162.
[30] DAMIANI A P, GARCEZ M L, LETIELI DE ABREU L, et al. A reduction in DNA damage in neural tissue and peripheral blood of old mice treated with caffeine[J]. J Toxicol Environ Health A, 2017, 80(13/14/15): 621-629.

Evaluation of genotoxicity of diphenhydramine hydrochloride and caffeine compound

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