甘露醇与葡萄糖水化可能会促进顺铂诱导的肾毒性:大鼠模型中顺铂治疗期间五种水化方案的测试

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

作者信息

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

机构信息

Water & Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Department of Internal Medicine, Oncology-Hematology Section, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

J Toxicol. 2021 Oct 4;2021:5547341. doi: 10.1155/2021/5547341. eCollection 2021.

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 ( < 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% ( < 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.

摘要

背景

顺铂(CP)仍是实体瘤治疗的一种新选择,但它伴有肾毒性副作用。水化可能会降低CP诱导的肾毒性风险,然而这一问题仍然具有挑战性。在本研究中,在CP治疗期间,对雄性和雌性大鼠均检测了包括生理盐水、甘露醇、葡萄糖盐水、生理盐水加呋塞米以及生理盐水加甘露醇在内的五种水化方案。

方法

将76只雄性和雌性Wistar大鼠分为14组进行CP治疗,实施五种水化方案,并通过生化标志物、肾功能参数和病理学检查评估诱导的肾毒性。

结果

雄性和雌性大鼠对水化方案类型有不同反应。接受甘露醇或葡萄糖水化类型的雌性大鼠死亡率较高。此外,在生理盐水加呋塞米或甘露醇加生理盐水治疗组水化的雌性大鼠中,血清尿素氮(BUN)、肌酐(Cr)水平和钠排泄分数(ENa%)升高,而Cr清除率(ClCr)显著降低(<0.05)。在甘露醇水化组中观察到雄性大鼠病情恶化,ClCr显著降低,血清BUN、Cr和ENa%显著升高(<0.05)。上述组中较高的肾组织损伤评分(KTDS)证实了这些发现。

结论

在CP治疗期间,甘露醇或葡萄糖水化会增加肾毒性风险,对雌性的影响更大。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eed7/8505073/122205e92275/JT2021-5547341.001.jpg

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