静脉注射顺铂并补充硫酸镁可能预防大鼠肾毒性：性别和硫酸镁剂量的作用
Intravenous Administration of Cisplatin with Magnesium Sulfate Supplement May Prevent Kidney Toxicity in Rats: The Role of Gender and Magnesium Sulfate Dose.
作者信息
Pournaderi Parisa, Pourvali Behnaz, Ashrafi Farzaneh, Talebi Ardeshir, Pezeshki Zahra, 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
Int J Nephrol. 2022 Feb 16;2022:1218222. doi: 10.1155/2022/1218222. eCollection 2022.
BACKGROUND
Cisplatin (CP) is widely used to treat various kinds of malignancies, but to avoid its side effects of nephrotoxicity and hypomagnesemia, magnesium supplementation is a subject of debate. The current study was designed to determine the protective role of intravenous magnesium sulfate (MgSO) against intravenous administration of CP in male and female rats.
METHOD
In this case-control experimental study, 80 Wistar male and female rats in 12 groups of experiments were subjected to receive intravenous administration of CP accompanied with intravenous infusion of different doses (1, 3, and 10 mg/ml solution) of MgSO and were compared with the control groups.
RESULTS
CP administration increased blood urea nitrogen (BUN), creatinine (Cr), kidney tissue damage score (KTDS), and kidney weight (KW), and they were attenuated by the mid-dose of MgSO supplementation in female rats. However, in male rats, the increase of Cr, BUN, KTDS, and KW induced by CP was ameliorated by low, mid-, and high doses of MgSO supplements. The levels of these markers were significantly different between male and female rats in the mid-dose of MgSO-treated group (BUN: =0.002, Cr: =0.005, KTDS: =0.002, and KW: =0.031). CP reduced clearance of Cr (ClCr) in both male and female rats significantly compared to the control group of saline alone ( = 0.002 and = 0.001), and the mid- and high doses of MgSO supplements improved ClCr in female rats. There were also sex differences in ClCr in mid- (=0.05) and high (=0.032) doses of MgSO-treated groups. CP accompanied with the mid-dose of MgSO supplement reduced the KTDS ( = 0.04 and = 0.004) and KW ( = 0.002 and = 0.042) in both male and female rats significantly when compared with the CP-alone-treated group, while there were also significant differences between the sexes (KTDS: =0.002 and KW: =0.031). CP accompanied with three different doses of MgSO supplements did not improve the serum levels of lactate dehydrogenase, urine level of sodium, malondialdehyde, urine flow, and nitrite statistically when compared with the CP-alone-treated group.
CONCLUSION
The renal protective effect of MgSO could be dose and gender related.
背景
顺铂（CP）广泛用于治疗各种恶性肿瘤，但为避免其肾毒性和低镁血症的副作用，补充镁存在争议。本研究旨在确定静脉注射硫酸镁（MgSO）对雄性和雌性大鼠静脉注射CP的保护作用。
方法
在本病例对照实验研究中，将80只Wistar雄性和雌性大鼠分为12组实验，接受静脉注射CP并同时静脉输注不同剂量（1、3和10mg/ml溶液）的MgSO，并与对照组进行比较。
结果
CP给药增加了血尿素氮（BUN）、肌酐（Cr）、肾组织损伤评分（KTDS）和肾重量（KW），而雌性大鼠补充中剂量MgSO可减轻这些指标。然而，在雄性大鼠中，低、中、高剂量的MgSO补充剂均可改善CP诱导的Cr、BUN、KTDS和KW的增加。在MgSO治疗组的中剂量时，这些指标在雄性和雌性大鼠之间存在显著差异（BUN：=0.002，Cr：=0.005，KTDS：=0.002，KW：=0.031）。与单独生理盐水对照组相比，CP显著降低了雄性和雌性大鼠的Cr清除率（ClCr）（=0.002和=0.001），中、高剂量的MgSO补充剂可改善雌性大鼠的ClCr。在MgSO治疗组的中剂量（=0.05）和高剂量（=0.032）时，ClCr也存在性别差异。与单独CP治疗组相比，CP联合中剂量MgSO补充剂显著降低了雄性和雌性大鼠的KTDS（=0.04和=0.004）和KW（=0.002和=0.042），同时性别之间也存在显著差异（KTDS：=0.002，KW：=0.031）。与单独CP治疗组相比，CP联合三种不同剂量的MgSO补充剂在统计学上并未改善血清乳酸脱氢酶水平、尿钠水平、丙二醛、尿流量和亚硝酸盐水平。
结论
MgSO的肾脏保护作用可能与剂量和性别有关。
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