PDF(Pubmed)
Abstract：
OBJECTIVE: Undernutrition is a serious health problem prevalent in poor countries, affecting millions of people worldwide, especially young children, pregnant women, and sick elderly individuals. This condition increases vulnerability to infections, leading to widespread use of antibiotic treatments in undernourished populations. The objective of the present study was to determine the in vivo genotoxic and cytotoxic effects of trimethoprim-sulfamethoxazole (TMP-SMX) treatment according to nutritional conditions.
METHODS: The effects of TMP-SMX treatment were measured by analyzing the kinetics of micronucleated reticulocytes (MN-RET) induced in the peripheral blood of young, well-nourished (WN) and undernourished (UN) rats.
RESULTS: In the WN group, two distinct peaks of MN-RET were observed, while the UN group had a significantly higher basal frequency of MN-RET compared to the WN group and only a later peak. Reticulocyte (RET) frequency slightly decreased in WN, indicating a poor cytotoxic effect. In contrast, in the UN, the treatment caused a significant increase in RET frequency. The results indicate that SMX\'s aromaticity index decreases when formed with TMP, suggesting potentially fewer toxic effects.
CONCLUSIONS: In vivo TMP-SMX produces two MN-RET induction peaks in WN animals, indicating two DNA damage induction mechanisms and consequent micronucleus production. The UN rats did not display the two peaks, indicating that the first MN induction mechanism did not occur in UN, possibly due to pharmacokinetic effects, decreased metabolism or effects on cell proliferation. TMP-SMX has a slight cytotoxic effect on WN. In contrast, in the UN, the antibiotic treatment seems to favor early erythropoiesis.
METHODS: The effects of TMP-SMX treatment were measured by analyzing the kinetics of micronucleated reticulocytes (MN-RET) induced in the peripheral blood of young, well-nourished (WN) and undernourished (UN) rats.
RESULTS: In the WN group, two distinct peaks of MN-RET were observed, while the UN group had a significantly higher basal frequency of MN-RET compared to the WN group and only a later peak. Reticulocyte (RET) frequency slightly decreased in WN, indicating a poor cytotoxic effect. In contrast, in the UN, the treatment caused a significant increase in RET frequency. The results indicate that SMX\'s aromaticity index decreases when formed with TMP, suggesting potentially fewer toxic effects.
CONCLUSIONS: In vivo TMP-SMX produces two MN-RET induction peaks in WN animals, indicating two DNA damage induction mechanisms and consequent micronucleus production. The UN rats did not display the two peaks, indicating that the first MN induction mechanism did not occur in UN, possibly due to pharmacokinetic effects, decreased metabolism or effects on cell proliferation. TMP-SMX has a slight cytotoxic effect on WN. In contrast, in the UN, the antibiotic treatment seems to favor early erythropoiesis.
摘要：
目的：营养不良是贫穷国家普遍存在的严重健康问题，影响着全世界数百万人，尤其是年幼的孩子，孕妇,和生病的老年人。这种情况增加了感染的脆弱性，导致在营养不良人群中广泛使用抗生素治疗。本研究的目的是根据营养状况确定甲氧苄啶-磺胺甲恶唑（TMP-SMX）治疗的体内遗传毒性和细胞毒性作用。
方法：通过分析青年外周血中诱导的微核网织红细胞（MN-RET）的动力学来测量TMP-SMX治疗的效果，营养良好（WN）和营养不良（UN）的老鼠。
结果：在WN组中，观察到两个不同的MN-RET峰，而与WN组相比，UN组的MN-RET的基础频率明显更高，并且只有一个较晚的峰值。网织红细胞（RET）频率在WN中略有下降，表明细胞毒性作用较差。相比之下,在联合国，治疗导致RET频率显著增加。结果表明，当与TMP形成时，SMX的芳香性指数降低，表明潜在的毒性作用更少。
结论：体内TMP-SMX在WN动物中产生两个MN-RET诱导峰，表明两种DNA损伤诱导机制和随之而来的微核产生。联合国老鼠没有显示两个峰，表明第一个MN诱导机制没有发生在联合国，可能是由于药代动力学效应,降低代谢或对细胞增殖的影响。TMP-SMX对WN具有轻微的细胞毒性作用。相比之下,在联合国，抗生素治疗似乎有利于早期红细胞生成。
方法：通过分析青年外周血中诱导的微核网织红细胞（MN-RET）的动力学来测量TMP-SMX治疗的效果，营养良好（WN）和营养不良（UN）的老鼠。
结果：在WN组中，观察到两个不同的MN-RET峰，而与WN组相比，UN组的MN-RET的基础频率明显更高，并且只有一个较晚的峰值。网织红细胞（RET）频率在WN中略有下降，表明细胞毒性作用较差。相比之下,在联合国，治疗导致RET频率显著增加。结果表明，当与TMP形成时，SMX的芳香性指数降低，表明潜在的毒性作用更少。
结论：体内TMP-SMX在WN动物中产生两个MN-RET诱导峰，表明两种DNA损伤诱导机制和随之而来的微核产生。联合国老鼠没有显示两个峰，表明第一个MN诱导机制没有发生在联合国，可能是由于药代动力学效应,降低代谢或对细胞增殖的影响。TMP-SMX对WN具有轻微的细胞毒性作用。相比之下,在联合国，抗生素治疗似乎有利于早期红细胞生成。
