Protective effect of rosmarinic acid on the transmembrane transporter Ctr1 expression in cisplatin-treated mice.

IF 50.5 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Nature Pub Date : 2023-10-01 Epub Date: 2022-09-10 DOI:10.4103/jcrt.jcrt_1428_21
Juheb Akhter, Poonam Goswami, Mirza Masroor Ali Beg, Shahzad Ahmad, Abul Kalam Najmi, Sheikh Raisuddin
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引用次数: 0

Abstract

Aims: Cisplatin (cis-diamminedichloroplatinum(II), CP) is a platinum-based anticancer drug widely used in the treatment of solid malignancies. However, its side effects, particularly nephrotoxicity, are limiting factors in its clinic use. Rosmarinic acid (RA), a natural antioxidant compound, is reported to attenuate oxidative stress and associated pathophysiological outcomes. Our study aimed to explore the protective effect of RA against CP-induced acute kidney injury (AKI).

Materials and methods: We investigated the effect of RA at the dose of 100 mg/kg on AKI induced by CP (20 mg/kg) in mice. Various parameters of nephrotoxicity such as levels of serum electrolytes, albumin, and globulin were measured using standardized methods. Besides, a specific biomarker of damage to proximal tubular cells, kidney injury molecule-1 (Kim-1), was measured in the serum by ELISA. mRNA expression of Kim-1 and a transmembrane transporter, copper transporter 1 (Ctr1), was analyzed by quantitative reverse transcriptase-polymerase chain reaction. CTR1 expression was also analyzed by western blot technique.

Results: RA treatment restored the downregulated CTR1 , a renal transmembrane transporter in CP-treated mice. It was accompanied by a reduction in the level of serum albumin and globulin. Serum electrolytes such as Na+, K+, and Ca2+ in CP-treated mice were found to be restored with RA treatment. Moreover, RA also significantly downregulated the increased expression of nephrotoxicity biomarker KIM-1.

Conclusions: Overall, RA proved to be an effective nephroprotective compound which afforded protection at cellular and subcellular levels with an appreciable modulatory effect on a transmembrane transporter.

迷迭香酸对顺铂治疗小鼠跨膜转运体 Ctr1 表达的保护作用
目的:顺铂(cis-diamminedichloroplatinum(II),CP)是一种以铂为基础的抗癌药物,广泛用于治疗实体恶性肿瘤。然而,它的副作用,尤其是肾毒性,是限制其临床应用的因素。据报道,天然抗氧化化合物迷迭香酸(RA)可减轻氧化应激和相关的病理生理结果。我们的研究旨在探讨 RA 对 CP 诱导的急性肾损伤(AKI)的保护作用:我们研究了 100 mg/kg 剂量的 RA 对 CP(20 mg/kg)诱导的小鼠 AKI 的影响。采用标准化方法测量了肾毒性的各种参数,如血清电解质、白蛋白和球蛋白的水平。此外,还通过酶联免疫吸附法测定了血清中近端肾小管细胞损伤的特异性生物标志物--肾损伤分子-1(Kim-1)。结果显示,RA 治疗恢复了下调的铜转运体 1(CTR1)表达:结果:RA 治疗恢复了 CP 治疗小鼠肾跨膜转运体 CTR1 的下调。与此同时,血清白蛋白和球蛋白水平也有所下降。CP 治疗小鼠的血清电解质(如 Na+、K+ 和 Ca2+)在 RA 治疗后得到恢复。此外,RA 还能显著降低肾毒性生物标志物 KIM-1 的表达:总之,RA 被证明是一种有效的肾脏保护化合物,可在细胞和亚细胞水平提供保护,并对跨膜转运体具有明显的调节作用。
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来源期刊
Nature
Nature 综合性期刊-综合性期刊
CiteScore
90.00
自引率
1.20%
发文量
3652
审稿时长
3 months
期刊介绍: Nature is a prestigious international journal that publishes peer-reviewed research in various scientific and technological fields. The selection of articles is based on criteria such as originality, importance, interdisciplinary relevance, timeliness, accessibility, elegance, and surprising conclusions. In addition to showcasing significant scientific advances, Nature delivers rapid, authoritative, insightful news, and interpretation of current and upcoming trends impacting science, scientists, and the broader public. The journal serves a dual purpose: firstly, to promptly share noteworthy scientific advances and foster discussions among scientists, and secondly, to ensure the swift dissemination of scientific results globally, emphasizing their significance for knowledge, culture, and daily life.
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