Calcium dobesilate prevents cisplatin-induced nephrotoxicity by modulating oxidative and histopathological changes in mi
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ORIGINAL ARTICLE
Calcium dobesilate prevents cisplatin-induced nephrotoxicity by modulating oxidative and histopathological changes in mice Gholamreza Bazmandegan 1,2 & Iman Fatemi 3 & Ayat Kaeidi 1,4 & Morteza Khademalhosseini 5,6 & Ali Fathinejad 7 & Morteza Amirteimoury 7 Received: 1 September 2020 / Accepted: 6 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Cisplatin is one of the synthetic cancer medicines with nephrotoxicity being one of its major side effects. Past research shows that calcium dobesilate (CaD), as a vascular protective agent in diabetic retinopathy, has antioxidant properties. Thus, this study aims to evaluate the protective effects of CaD in cisplatin-induced nephrotoxicity in mice. A many as 28 mice, in the present experimental research, were randomly distributed into four groups, including control, cisplatin (the intraperitoneal administration of 20 mg/kg cisplatin only on the first day of the experiment), cisplatin + CaD 50 (cisplatin with the oral administration of 50 mg/kg CaD), and cisplatin + CaD 100 (cisplatin with the oral administration of 100 mg/kg CaD). The treated groups received CaD by oral gavage for 4 constitutive days. On the fifth day, the mice were sacrificed, and some biochemical (serum levels of Cr and BUN, renal tissue levels of MDA, and renal activities of SOD and GPx) and pathological parameters were evaluated. Based on the results, there was a significant decrease in the renal SOD and GPx activities; in contrast, there was a significant increase in the BUN, Cr, and renal MDA levels following administering cisplatin. However, the CaD treatment (100 mg/kg) significantly attenuated these alterations. In addition, the kidney’s histological examination of kidneys confirmed the nephroprotective effects of CaD. The findings proved the protective impact of CaD on cisplatin-induced nephrotoxicity by an improvement in the oxidative stress factors. Keywords Nephrotoxicity . Cisplatin . Calcium dobesilate . Antioxidant . Mice
Introduction Cisplatin is a well-known chemotherapeutic drug with cellular alkylating properties, which is used in the treatment of cancers, such as brain cancer, carcinoma, lung cancer, and ovarian cancer (Yao et al. 2007). Cisplatin-induced nephrotoxicity
is the major side effect that limits its clinical use (Goudarzi et al. 2017b; Sharp and Siskind 2017). There are several mechanisms involved in nephrotoxicity induced by cisplatin. One of the major mechanisms of this type is the overproduction of reactive oxygen species (ROS) and tissue oxidative damage (Ozkok and Edelstein 2014; Bazmandegan et al.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00210-020-01990-3) contains supplementary material, which is available to authorized users. * Morteza Amirteimoury [email protected]; [email protected]
4
Department of Physiology and Pharmacology, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
1
Physiology-Pharmacology Research Center, Research In
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