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研究氟喹诺酮类抗菌药物对非细菌性发热模型小鼠的降温作用。

Investigating the hypothermic effects of fluoroquinolone antimicrobials on non-bacterial fever model mice.

作者信息

Hara Ryohei, Taguchi Kazuaki, Ogino Hiromi, Okamoto Yuko, Enoki Yuki, Kizu Junko, Hori Seiji, Matsumoto Kazuaki

机构信息

Division of Pharmacodynamics, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-Ku, Tokyo, 105-8512, Japan.

Division of Practical Pharmacy, Faculty of Pharmacy, Keio University, Tokyo, Japan.

出版信息

J Pharm Health Care Sci. 2024 Nov 4;10(1):68. doi: 10.1186/s40780-024-00392-4.

Abstract

BACKGROUND

Fluoroquinolone (FQ) antimicrobials have antipyretic effects during the treatment of bacterial infections; however, it is not clear whether these are due to their antimicrobial activities or their hypothermic effects. In this study, we investigated the hypothermic effects of FQ antimicrobials (ciprofloxacin [CPFX], gatifloxacin [GFLX], and levofloxacin [LVFX]) on fever by evaluating rectal body temperature changes in a mouse model of non-bacterial fever.

METHODS

CPFX, GFLX, and LVFX were administered intraperitoneally to non-bacterial fever model mice induced by yeast. Rectal body temperature was measured up to 180 min after administration.

RESULTS

A decrease in rectal body temperature of up to 1.2 °C for CPFX, 3.4 °C for GFLX, and 1.0 °C for LVFX was observed. The decrease in temperature was induced by an increase in the plasma concentration of FQ antimicrobials, suggesting that they are responsible for the temperature reduction. Focusing on glucocorticoids, one thermoregulation mechanism, we investigated the substances responsible for the reduction in rectal body temperature induced by FQ antimicrobials. Aminoglutethimide (an inhibitor of glucocorticoid production) were premedicated, followed by intraperitoneal administration of GFLX in the yeast-induced fever mouse model, resulting in attenuated GFLX-induced hypothermic effects.

CONCLUSIONS

These results suggest that certain antipyretic effects of CPFX, GFPX, and LVFX during fever may contribute to their hypothermic effects; certain mechanisms are glucocorticoid-mediated.

摘要

背景

氟喹诺酮(FQ)类抗菌药物在治疗细菌感染过程中具有退热作用;然而,尚不清楚这些作用是由于其抗菌活性还是降温作用。在本研究中,我们通过评估非细菌性发热小鼠模型的直肠体温变化,研究了FQ类抗菌药物(环丙沙星[CPFX]、加替沙星[GFLX]和左氧氟沙星[LVFX])的降温作用。

方法

将CPFX、GFLX和LVFX腹腔注射给酵母诱导的非细菌性发热模型小鼠。给药后长达180分钟测量直肠体温。

结果

观察到CPFX使直肠体温下降高达1.2℃,GFLX为3.4℃,LVFX为1.0℃。体温下降是由FQ类抗菌药物血浆浓度升高引起的,表明它们是体温降低的原因。着眼于糖皮质激素这一体温调节机制,我们研究了导致FQ类抗菌药物引起直肠体温下降的物质。在酵母诱导的发热小鼠模型中,预先给予氨鲁米特(一种糖皮质激素生成抑制剂),然后腹腔注射GFLX,导致GFLX诱导的降温作用减弱。

结论

这些结果表明,CPFX、GFPX和LVFX在发热期间的某些退热作用可能归因于其降温作用;某些机制是由糖皮质激素介导的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c42f/11533349/fd581752d2df/40780_2024_392_Fig1_HTML.jpg

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