Hasanpour Zahra, Choopani Samira, Ashrafi Farzaneh, Talebi Ardeshir, Nematbaksh Mehdi
Department of Internal Medicine, Oncology-Hematology Section, Isfahan University of Medical Sciences, Isfahan, Iran.
Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Adv Biomed Res. 2024 Feb 26;13:14. doi: 10.4103/abr.abr_269_22. eCollection 2024.
High-dose methotrexate (HDMTX) as a cytotoxic agent might cause various side effects. Hyperhydration has been implemented as the major strategy to decrease the potential risk of toxicities induced by HDMTX. This study aims to assess the renoprotective effect of hydration with dextrose water (DW) 5% versus normal saline (N/S) 0.9% against methotrexate (MTX) induced nephrotoxicity.
This experimental animal study has been conducted on 36 Wistar rats (200-250 g) categorized into six groups, including male ( = 6) and female ( = 6) rats receiving sodium chloride 0.9% saline plus MTX, DW 5% plus MTX, or MTX alone. By the fifth day after the MTX injection, biochemical indexes were measured. The rats were also sacrificed and renal specimens were evaluated microscopically to determine kidney tissue damage (KTD).
The groups were not significantly different with regard to blood urea nitrogen (BUN) ( = 0.5), creatinine (Cr) ( = 0.24), kidney weight ( = 0.34), and urine flow (UF) ( = 0.5), while KTD score was remarkably less in the hydrated groups ( < 0.001). Weight loss in DW-treated rats was significantly more than N/S-treated ones, and creatinine clearance (CrCl) and urine load (UL) of Cr were statistically similar between males and females in the control group, but significantly lower among the DW5% treated males.
Based on the findings of this study, hydration with N/S was superior to DW5% for the prevention from HDMTX-induced nephrotoxicity. Besides, we found insignificant differences between male versus female rats in response to the hydration for HDMTX-induced renoprotection; however, females probably benefit more.
高剂量甲氨蝶呤（HDMTX）作为一种细胞毒性药物可能会引起各种副作用。补液已成为降低HDMTX诱导毒性潜在风险的主要策略。本研究旨在评估5%葡萄糖水（DW）与0.9%生理盐水（N/S）补液对甲氨蝶呤（MTX）诱导的肾毒性的肾脏保护作用。
本实验动物研究对36只体重200 - 250克的Wistar大鼠进行，分为六组，包括接受0.9%氯化钠盐水加MTX、5% DW加MTX或单独MTX的雄性（每组6只）和雌性（每组6只）大鼠。在MTX注射后的第五天，测量生化指标。大鼠处死后，对肾脏标本进行显微镜评估以确定肾组织损伤（KTD）。
各组在血尿素氮（BUN）（P = 0.5）、肌酐（Cr）（P = 0.24）、肾脏重量（P = 0.34）和尿流量（UF）（P = 0.5）方面无显著差异，而补液组的KTD评分显著更低（P < 0.001）。DW处理组大鼠的体重减轻明显多于N/S处理组，对照组中雄性和雌性的肌酐清除率（CrCl）和Cr的尿排泄量（UL）在统计学上相似，但DW5%处理组的雄性大鼠显著更低。
基于本研究结果，N/S补液在预防HDMTX诱导的肾毒性方面优于DW5%。此外，我们发现雄性和雌性大鼠在对HDMTX诱导的肾脏保护的补液反应方面无显著差异；然而，雌性可能受益更多。
