Hydration with Mannitol and Dextrose May Promote Cisplatin-Induced Nephrotoxicity: Test of Five Protocols of Hydration during Cisplatin Therapy in Rat Models.

IF 3.4 Q2 TOXICOLOGY

Journal of Toxicology Pub Date : 2021-10-04 eCollection Date: 2021-01-01 DOI:10.1155/2021/5547341

Mohammad-Sedigh Khosravi, Alireza Samimiat, Bahar Mazaheri, Farzaneh Ashrafi, Ardeshir Talebi, Mehdi Nematbakhsh

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引用次数: 3

Abstract

Backgrounds: Cisplatin (CP) still is a novel choice for solid tumor therapy, but it is accompanied with the side effect of nephrotoxicity. Hydration may reduce the risk of CP-induced nephrotoxicity, while the issue is still challenging. In this study, five types of hydration protocols including saline, mannitol, dextrose saline, saline plus furosemide, and saline plus mannitol were examined in both sexes of rats during CP therapy.

Methods: Seventy-six male and female Wistar rats in 14 groups of experiments were subjected to CP therapy, and five types of hydration protocols were implemented, and the induced nephrotoxicity was evaluated via biochemical markers, kidney function parameters, and pathology investigation.

Results: Male and female rats had different responses to hydration protocol types. The higher mortality rate was seen in female rats that received mannitol or dextrose hydration types. In addition, the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and sodium excretion fraction (ENa%) increased and the clearance of Cr (ClCr) decreased significantly (P < 0.05) in female rats hydrated with saline plus furosemide or mannitol plus saline-treated groups. The worsened condition in male rats is observed in the mannitol hydration group with a significant decrease of ClCr and significant increase of serum BUN and Cr and ENa% (P < 0.05). The higher kidney tissue damage score (KTDS) in the mentioned groups verified the findings.

Conclusion: Hydration with mannitol or dextrose promotes the risk of nephrotoxicity during CP therapy with more intensity on the female.

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甘露醇和葡萄糖水合可促进顺铂引起的肾毒性:大鼠模型顺铂治疗期间5种水合方案的试验

背景:顺铂(CP)仍是实体瘤治疗的新选择，但伴随有肾毒性的副作用。水合作用可能会降低cp引起的肾毒性的风险，但这个问题仍然具有挑战性。本研究采用生理盐水、甘露醇、葡萄糖盐水、生理盐水加呋塞米、生理盐水加甘露醇等5种水化方案，对两性大鼠进行CP治疗。方法:采用CP治疗14组Wistar大鼠76只，采用5种不同的水化方案，通过生化指标、肾功能指标和病理检查评价其肾毒性。结果:雌雄大鼠对不同补水方案的反应不同。服用甘露醇或葡萄糖水合型的雌性大鼠死亡率较高。生理盐水加呋塞米组和甘露醇加生理盐水组大鼠血清尿素氮(BUN)、肌酐(Cr)水平和钠排泄分数(ENa%)显著升高，Cr (ClCr)清除率显著降低(P < 0.05)。甘露醇水合组雄性大鼠ClCr显著降低，血清BUN、Cr、ENa%显著升高(P < 0.05)。上述组较高的肾组织损伤评分(KTDS)证实了这一发现。结论:甘露醇或葡萄糖水合可增加CP治疗期间肾毒性的风险，且对女性的影响更大。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Toxicology TOXICOLOGY-

CiteScore

5.50

自引率

3.40%

发文量

审稿时长

10 weeks

期刊介绍： Journal of Toxicology is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies in all areas of toxicological sciences. The journal will consider articles looking at the structure, function, and mechanism of agents that are toxic to humans and/or animals, as well as toxicological medicine, risk assessment, safety evaluation, and environmental health.