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暴露于高压氧会加重万古霉素诱导的大鼠肾毒性。

Exposure to Hyperbaric Oxygen Intensified Vancomycin-Induced Nephrotoxicity in Rats.

作者信息

Sabler Itay M, Berkovitch Matitiahu, Sandbank Judith, Kozer Eran, Dagan Zahi, Goldman Michael, Bahat Hilla, Stav Kobi, Zisman Amnon, Klin Baruch, Abu-Kishk Ibrahim

机构信息

Department of Urology, Assaf Harofeh Medical Center, Zerifin, affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Clinical Pharmacology Unit, Assaf Harofeh Medical Center, Zerifin, affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

出版信息

PLoS One. 2016 Apr 19;11(4):e0152554. doi: 10.1371/journal.pone.0152554. eCollection 2016.

Abstract

It has been suggested that oxidative stress is a potential mechanism for vancomycin-induced nephrotoxicity and hyperbaric oxygen therapy (HBO) has been shown to be effective in treating renal toxicity that has been pharmacologically induced in animal models. The aim of this study was to investigate the effect of HBO therapy on vancomycin-induced nephrotoxicity in rats. The study group comprised 36 Sprague Dawley male rats. We treated 30 with 500 mg/kg of intraperitoneal vancomycin once a day for 7 days. Half of these rats received a daily 1-hour treatment with HBO at 2 Atmospheres (ATM) on the same 7 days and formed the HBO+ group. The other 15 subjects received no HBO treatment (HBO- group). The remaining six rats served as the control group, three received HBO treatments alone and no treatment was administered to the other three rats. Laboratory results were obtained on day 8 and the intervention and control groups were compared. Rats in the HBO+ group gained less weight than the HBO- group (11.6 grams vs 22.6 grams; P = 0,008) and had significantly higher serum blood urea nitrogen (99.6 vs 52.6 mg/dL; P<0.001), serum creatinine (0.42 vs 0.16 mg/dL; P = 0.001) and magnesium (3.6 vs 3.1 mg/dL; P = 0.014). The vancomycin blood levels were also higher in the HBO+ group (27.8 vs 6.7 μg/mL; P = 0.078). There were no pathological kidney changes in the control group. All the kidneys from the treated groups (vancomycin +HBO and vancomycin HBO-) showed moderate to severe histopathological changes with no statistical significance between them. This study demonstrated that exposure to hyperbaric oxygen intensified vancomycin-induced nephrotoxicity in rats.

摘要

有人提出氧化应激是万古霉素诱导肾毒性的潜在机制,并且高压氧疗法(HBO)已被证明可有效治疗动物模型中药物诱导的肾毒性。本研究的目的是探讨HBO疗法对大鼠万古霉素诱导肾毒性的影响。研究组包括36只雄性Sprague Dawley大鼠。我们对30只大鼠每天腹腔注射500 mg/kg万古霉素,持续7天。在这7天中,其中一半大鼠每天接受1小时2个大气压(ATM)的HBO治疗,形成HBO+组。另外15只大鼠未接受HBO治疗(HBO-组)。其余6只大鼠作为对照组,3只仅接受HBO治疗,另外3只未接受任何治疗。在第8天获得实验室结果,并对干预组和对照组进行比较。HBO+组大鼠体重增加量低于HBO-组(11.6克对22.6克;P = 0.008),血清血尿素氮(99.6对52.6 mg/dL;P<0.001)、血清肌酐(0.42对0.16 mg/dL;P = 0.001)和镁(3.6对3.1 mg/dL;P = 0.014)显著更高。HBO+组的万古霉素血药浓度也更高(27.8对6.7 μg/mL;P = 0.078)。对照组肾脏无病理改变。所有治疗组(万古霉素+HBO组和万古霉素HBO-组)的肾脏均显示中度至重度组织病理学改变,两组之间无统计学差异。本研究表明,暴露于高压氧会加剧大鼠万古霉素诱导的肾毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebb6/4836689/b6badeb77fc3/pone.0152554.g001.jpg

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