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. 2023 Oct 1;19(7):1753-1759.
doi: 10.4103/jcrt.jcrt_1428_21. Epub 2022 Sep 10.

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

Juheb Akhter  1 , Poonam Goswami  1 , Mirza Masroor Ali Beg  1   2 , Shahzad Ahmad  1 , Abul Kalam Najmi  3 , Sheikh Raisuddin  1
Affiliations
Free article

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

Juheb Akhter et al. J Cancer Res Ther. .
Free article

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.

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