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英夫利昔单抗、二甲基富马酸(DMF)及其联合应用对环丙沙星诱导雄性大鼠肾毒性的潜在影响。

The potential effect of infliximab, dimethyl fumarate (DMF), and their combination in ciprofloxacin-induced renal toxicity in male rats.

机构信息

Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq.

Department of Pharmacology and Toxicology, College of Pharmacy, University of Kerbala, Kerbala, Iraq.

出版信息

J Med Life. 2023 Mar;16(3):477-480. doi: 10.25122/jml-2022-0197.

DOI:10.25122/jml-2022-0197
PMID:37168296
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10165515/
Abstract

The aim of this study was to evaluate the effectiveness of infliximab and dimethyl fumarate (DMF) in reducing renal damage induced by ciprofloxacin. Forty rats were divided into five groups of eight each, with normal saline and CIP 600 mg IP administered to all animals in Groups 1 and 2 for ten days. Groups 3 and 4 were administered infliximab 7 mg/kg and DMF 30 mg/kg 24 hours before the CIP injections. Group 5 received a combination of infliximab/DMF after 24 hours of CIP. The levels of TNF-α, NF-Bp65, and IL-6 were measured, and the results showed that both infliximab and DMF had similar effects. However, the combination of infliximab and DMF had a robust anti-inflammatory and antiapoptotic impact, reducing TNF-α, NF-Bp65, IL-6, and Bcl-2 compared to the renal control group. Bcl-2 immuno-expression was lower in the ciprofloxacin group compared to the control group. DMF and infliximab had no effect on Bcl-2-positive cells, whereas infliximab increased the percentage of Bcl-2-positive cells substantially. CIP induced nephrotoxicity by increasing cytokine release and cell death signaling. Both infliximab and DMF are powerful TNF-α blockers that suppress cytokine release, preventing cell death and apoptosis caused by cytokines. Controlling inflammation and apoptosis can prevent nephrotoxicity.

摘要

本研究旨在评估英夫利昔单抗和二甲基富马酸(DMF)在减少环丙沙星诱导的肾损伤方面的有效性。将 40 只大鼠分为五组,每组 8 只,所有动物均在第 1 组和第 2 组中接受生理盐水和 CIP 600 mg IP 连续 10 天。第 3 组和第 4 组在 CIP 注射前 24 小时给予英夫利昔单抗 7 mg/kg 和 DMF 30 mg/kg。第 5 组在 CIP 后 24 小时给予英夫利昔单抗/ DMF 联合治疗。测量 TNF-α、NF-Bp65 和 IL-6 水平,结果表明英夫利昔单抗和 DMF 具有相似的作用。然而,英夫利昔单抗和 DMF 的联合使用具有强大的抗炎和抗凋亡作用,与肾对照组相比,TNF-α、NF-Bp65、IL-6 和 Bcl-2 均降低。与对照组相比,环丙沙星组的 Bcl-2 免疫表达较低。DMF 和英夫利昔单抗对 Bcl-2 阳性细胞没有影响,而英夫利昔单抗则显著增加 Bcl-2 阳性细胞的百分比。CIP 通过增加细胞因子释放和细胞死亡信号诱导肾毒性。英夫利昔单抗和 DMF 都是强大的 TNF-α 阻滞剂,可抑制细胞因子释放,防止细胞因子引起的细胞死亡和凋亡。控制炎症和凋亡可以预防肾毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc7d/10165515/686ddb2988ef/JMedLife-16-477-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc7d/10165515/2ba3d7b1c42d/JMedLife-16-477-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc7d/10165515/686ddb2988ef/JMedLife-16-477-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc7d/10165515/2ba3d7b1c42d/JMedLife-16-477-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc7d/10165515/686ddb2988ef/JMedLife-16-477-g002.jpg

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本文引用的文献

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Safety study of Ciprofloxacin in newborn mice.环丙沙星在新生小鼠中的安全性研究。
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