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对哺乳期Wistar大鼠给予利奈唑胺会影响其后代的健康。

Linezolid administration to lactating Wistar rats affects the health of their offspring.

作者信息

Hamouda Aya G, Abd-Allah Entsar R, Mahmoud Aya A

机构信息

Zoology Department, Faculty of Science, Cairo University, Giza, Egypt.

Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Egypt.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 12. doi: 10.1007/s00210-025-04060-8.

Abstract

Lactational exposure to antibacterial medications may affect the normal development of newborns during this crucial stage and later in adult life. Linezolid (LNZ) is an oxazolidinone antibacterial drug that is effective against drug-resistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis. Although it is relatively toxic, there is insufficient data about LNZ use during lactation. This study aimed to elucidate the impact of linezolid administration during lactation on Wistar rats' offspring. Eighteen lactating Wistar female rats were separated into three groups (n = 6): control, therapeutic, and low dose groups. The therapeutic dose group received 61.66 mg/kg of LNZ (equivalent to the human dose), while the low dose group received 15.41 mg/kg of LNZ (1/4 of the human therapeutic dose) by gavage twice daily. All lactating dams and their offspring died four days after receiving a therapeutic dose. In the low dose group, LNZ significantly reduced the body weight of lactating females and their pups. The liver tissue of the pups showed a considerable increase in malondialdehyde levels, along with a decrease in the catalase, glutathione, and superoxide dismutase activities accompanied by moderate histological alterations like congestion, and infiltration, and DNA fragmentation as indicated by comet assay. Microscopic examination of renal tissue revealed glomeruli deterioration, cellular infiltration, and intratubular protein deposits. In conclusion, this study highlights the potential risks linezolid may pose to infants during postpartum. Therefore, there is a need for preweaning monitoring and caution should be taken during breastfeeding.

摘要

哺乳期接触抗菌药物可能会影响新生儿在这一关键阶段以及成年后的正常发育。利奈唑胺(LNZ)是一种恶唑烷酮类抗菌药物,对耐药革兰氏阳性菌和多重耐药结核分枝杆菌有效。尽管其毒性相对较大,但关于哺乳期使用利奈唑胺的数据不足。本研究旨在阐明哺乳期给予利奈唑胺对Wistar大鼠后代的影响。18只哺乳期Wistar雌性大鼠被分为三组(n = 6):对照组、治疗组和低剂量组。治疗剂量组通过每日两次灌胃给予61.66 mg/kg的利奈唑胺(相当于人类剂量),而低剂量组给予15.41 mg/kg的利奈唑胺(人类治疗剂量的1/4)。所有哺乳期母鼠及其后代在接受治疗剂量后四天死亡。在低剂量组中,利奈唑胺显著降低了哺乳期雌性大鼠及其幼崽的体重。幼崽的肝脏组织丙二醛水平显著升高,同时过氧化氢酶、谷胱甘肽和超氧化物歧化酶活性降低,并伴有中度组织学改变,如充血、浸润,彗星试验显示有DNA片段化。肾脏组织的显微镜检查显示肾小球恶化、细胞浸润和肾小管内蛋白质沉积。总之,本研究强调了利奈唑胺在产后可能对婴儿造成的潜在风险。因此,需要在断奶前进行监测,母乳喂养期间应谨慎。

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