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没食子酸和/或速尿对托吡酯诱导的雄性大鼠肾功能损害的改善作用。

The ameliorative effect of gallic acid and/or Lasix on topiramate-induced renal impairment in male rats.

作者信息

Ramadan Rana, El-Sherbini El-Said, Elsayed Gehad, El-Adl Mohamed

机构信息

Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.

Department of Basic Veterinary Science, Faculty of Veterinary Medicine, Delta University for Science and Technology, Mansoura, Egypt.

出版信息

Open Vet J. 2025 Apr;15(4):1823-1835. doi: 10.5455/OVJ.2025.v15.i4.35. Epub 2025 Apr 30.

DOI:10.5455/OVJ.2025.v15.i4.35
PMID:40453839
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12124778/
Abstract

BACKGROUND

Topiramate (TPM) is commonly used for migraine prophylaxis; nonetheless, it is linked to nephrotoxicity, which mostly results from oxidative stress and inflammatory mechanisms.

AIM

This study aimed to assess the preventive effects of gallic acid (GA) and furosemide (Lasix) against renal damage caused by TPM in rats.

METHODS

Sixty male albino rats were categorized into six groups: control, TPM-only, TPM + Lasix, Lasix-only, TPM + GA, and GA-only. The investigation lasted 60 days, evaluating renal function, oxidative stress indicators, and histological and immunohistochemical alterations.

RESULTS

The TPM-treated group exhibited considerable renal impairment, as indicated by increased levels of creatinine, urea, blood urea nitrogen, and interleukin (IL)-6, as well as reduced activity of antioxidant enzymes [catalase (CAT), superoxide dismutase]. Histopathological examination revealed tubular necrosis and inflammation, while immunohistochemistry results showed elevated expression of caspase3 and IL-6. The co-administration of GA or Lasix mitigated these effects. The TPM + GA group exhibited improved kidney function, less oxidative stress, and enhanced histological structure, underscoring GA's powerful antioxidant and anti-inflammatory characteristics. Likewise, Lasix exerted protective effects by alleviating TPM-induced kidney injury.

CONCLUSION

These data highlight the therapeutic efficacy of GA and Lasix against TPM-induced nephrotoxicity, indicating their clinical relevance in addressing drug-induced kidney damage.

摘要

背景

托吡酯(TPM)常用于偏头痛预防;然而,它与肾毒性有关,这主要是由氧化应激和炎症机制引起的。

目的

本研究旨在评估没食子酸(GA)和呋塞米(速尿)对TPM诱导的大鼠肾损伤的预防作用。

方法

将60只雄性白化大鼠分为六组:对照组、仅TPM组、TPM + 速尿组、仅速尿组、TPM + GA组和仅GA组。研究持续60天,评估肾功能、氧化应激指标以及组织学和免疫组化改变。

结果

TPM治疗组表现出明显的肾损伤,表现为肌酐、尿素、血尿素氮和白细胞介素(IL)-6水平升高,以及抗氧化酶[过氧化氢酶(CAT)、超氧化物歧化酶]活性降低。组织病理学检查显示肾小管坏死和炎症,而免疫组化结果显示caspase3和IL-6表达升高。GA或速尿的联合使用减轻了这些影响。TPM + GA组肾功能改善,氧化应激减轻,组织结构增强,突出了GA强大的抗氧化和抗炎特性。同样,速尿通过减轻TPM诱导的肾损伤发挥保护作用。

结论

这些数据突出了GA和速尿对TPM诱导的肾毒性的治疗效果,表明它们在解决药物性肾损伤方面的临床相关性。

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本文引用的文献

1
The Potential Health Benefits of Gallic Acid: Therapeutic and Food Applications.没食子酸对健康的潜在益处:治疗及食品应用
Antioxidants (Basel). 2024 Aug 18;13(8):1001. doi: 10.3390/antiox13081001.
2
The relationship between anti-seizures medications and metabolic acidosis in craniotomy operations: is topiramate or zonisamide the cause of metabolic acidosis?抗癫痫药物与开颅手术中代谢性酸中毒的关系:是托吡酯还是唑尼沙胺导致代谢性酸中毒?
BMC Anesthesiol. 2024 Aug 27;24(1):296. doi: 10.1186/s12871-024-02677-5.
3
Mechanisms of neurodevelopmental toxicity of topiramate.
托吡酯的神经发育毒性机制。
Crit Rev Toxicol. 2024 Aug;54(7):465-475. doi: 10.1080/10408444.2024.2368552. Epub 2024 Jul 12.
4
Exposure to topiramate and acetazolamide causes endocrine disrupting effects in female rats during estrus.暴露于托吡酯和乙酰唑胺会在雌性大鼠发情期对其产生内分泌干扰作用。
Toxicol Appl Pharmacol. 2024 May;486:116919. doi: 10.1016/j.taap.2024.116919. Epub 2024 Apr 3.
5
Gallic acid rescues uranyl acetate induced-hepatic dysfunction in rats by its antioxidant and cytoprotective potentials.没食子酸通过抗氧化和细胞保护作用,挽救醋酸铀酰所致大鼠肝损伤。
BMC Complement Med Ther. 2023 Nov 22;23(1):423. doi: 10.1186/s12906-023-04250-y.
6
Targeting Autophagy, Apoptosis, and SIRT1/Nrf2 Axis with Topiramate Underlies Its Neuroprotective Effect against Cadmium-Evoked Cognitive Deficits in Rats.托吡酯靶向自噬、细胞凋亡以及SIRT1/Nrf2轴是其对镉诱发的大鼠认知缺陷具有神经保护作用的基础。
Pharmaceuticals (Basel). 2023 Aug 29;16(9):1214. doi: 10.3390/ph16091214.
7
The protective effects of topiramate and spirulina against doxorubicin-induced cardiotoxicity in rats.托吡酯和螺旋藻对阿霉素诱导的大鼠心脏毒性的保护作用。
Hum Exp Toxicol. 2023 Jan-Dec;42:9603271231198624. doi: 10.1177/09603271231198624.
8
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Naunyn Schmiedebergs Arch Pharmacol. 2024 Feb;397(2):1141-1149. doi: 10.1007/s00210-023-02677-1. Epub 2023 Aug 26.
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Furosemide exacerbated the impairment of renal function, oxygenation and medullary damage in a rat model of renal ischemia/reperfusion induced AKI.在肾缺血/再灌注诱导的急性肾损伤大鼠模型中,呋塞米加剧了肾功能损害、氧合作用及髓质损伤。
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