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二甲基亚砜与烷基化剂N-甲基-N-亚硝基脲联合使用对小鼠的毒性:聚焦于死亡率和活动能力损害

The Toxicity of Dimethyl Sulfoxide Combined with the Alkylating Agent MNU on Mice: Focusing on Mortality and Activity Impairment.

作者信息

Yan Weiming, He Qiurui, Xiao Lin, Xia Yuxin, Zheng Xiangrong, Zhang Xiaohong

机构信息

Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350025, People's Republic of China.

The Third Hospital of Zhangzhou, Zhangzhou, 363005, People's Republic of China.

出版信息

Drug Des Devel Ther. 2025 Jul 5;19:5727-5737. doi: 10.2147/DDDT.S521506. eCollection 2025.

DOI:10.2147/DDDT.S521506
PMID:40642425
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12241661/
Abstract

OBJECTIVE

Dimethyl sulfoxide (DMSO) is known to enhance the absorption of chemicals. This study investigated the effects of DMSO in combination with the alkylating agent, N-methyl-N-nitrosourea (MNU), on the activity and mortality of mice, providing foundational data for solvent mixture use and health impact assessment.

METHODS

Twelve male SPF C57BL/6J mice were divided into three groups (n=4): DMSO group (D), DMSO combined with low-dose (L), and high-dose MNU group (H). Mice in D received intraperitoneal injections of pure DMSO solution at 12 mL/kg. The L or D group was injected with a DMSO solution containing 40 mg/kg or 60 mg/kg MNU at 12 mL/kg, respectively. Mice were monitored for changes in body weight, activity levels (walking, body stretching, fur condition), and mortality at various time points.

RESULTS

Pre-injection, all groups showed no statistical differences in weight or DMSO dose, while the MNU injection dose was significantly different (H>L>D). Within 2 hours post-injection, all mice except one in the D group exhibited reduced mobility, hunched posture, and lethargy. Mortality progressed rapidly, with one D and two L mice dying by 12 hours, followed by additional deaths (one D, two L, and two H mice) at 24 hours. By 36 hours, all mice in L and H groups had died, while one D mouse recovered normal activity. At the 48-hour endpoint, only one D mouse survived with normal behavior. No significant differences in weight, activity levels and mortality changes were observed in surviving mice throughout the study period.

CONCLUSION

DMSO has certain toxicity, and when combined with alkylating agents such as MNU, it can lead to reduced activity and an increased mortality rate in mice. It is recommended to closely monitor the mice during the use of such reagents and to establish appropriate research observation protocols.

摘要

目的

已知二甲基亚砜(DMSO)可增强化学物质的吸收。本研究调查了DMSO与烷基化剂N-甲基-N-亚硝基脲(MNU)联合使用对小鼠活性和死亡率的影响,为溶剂混合物的使用和健康影响评估提供基础数据。

方法

将12只雄性SPF C57BL/6J小鼠分为三组(n = 4):DMSO组(D)、DMSO与低剂量(L)和高剂量MNU联合组(H)。D组小鼠腹腔注射12 mL/kg的纯DMSO溶液。L组或H组分别注射含40 mg/kg或60 mg/kg MNU的DMSO溶液,剂量为12 mL/kg。在各个时间点监测小鼠体重、活性水平(行走、身体伸展、皮毛状况)和死亡率的变化。

结果

注射前,所有组在体重或DMSO剂量方面无统计学差异,而MNU注射剂量有显著差异(H>L>D)。注射后2小时内,除D组的一只小鼠外,所有小鼠均表现出活动减少、弓背姿势和嗜睡。死亡率迅速上升,12小时时有1只D组和2只L组小鼠死亡,随后在24小时时有更多小鼠死亡(1只D组、2只L组和2只H组)。到36小时时,L组和H组的所有小鼠均死亡,而1只D组小鼠恢复了正常活动。在48小时的终点,只有1只D组小鼠存活且行为正常。在整个研究期间,存活小鼠的体重、活性水平和死亡率变化均未观察到显著差异。

结论

DMSO具有一定毒性,与MNU等烷基化剂联合使用时,可导致小鼠活性降低和死亡率增加。建议在使用此类试剂时密切监测小鼠,并建立适当的研究观察方案。

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