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环境病理学,毒理学和肿瘤学期刊
影响因子: 1.625 5年影响因子: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN 打印: 0731-8898
ISSN 在线: 2162-6537

环境病理学,毒理学和肿瘤学期刊

DOI: 10.1615/JEnvironPatholToxicolOncol.2019028294
pages 153-163

Rutin Protects against Doxorubicin-Induced Cognitive Dysfunction While Retaining the Anticancer Potential of Dox in a Murine Model of N-Methyl-N-Nitrosourea – Induced Mammary Carcinoma

Grandhi Venkata Ramalingayya
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal–576104, Karnataka, India; Discovery Biology, Suven Life Sciences Ltd., Hyderabad, Telangana, India
Karthik Gourishetti
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal–576104, Karnataka, India
Pawan G. Nayak
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal – 576104, Karnataka, India
Chamallamudi Mallikarjuna Rao
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India-576104
Anoop Kishore
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal – 576104, Karnataka, India
Sulaiman M. Alnaseer
Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Unaizah, Kingdom of Saudi Arabia
Shalam M. Hussain
Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Unaizah, Kingdom of Saudi Arabia
Krishnadas Nandakumar
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal – 576104, Karnataka, India

ABSTRACT

Chemobrain is a significant post-chemotherapy complication for which no approved treatments are available. We had previously identified that rutin inhibits doxorubicin (Dox-) –induced cognitive decline in healthy rats. However, it was important to also establish that it does so in rats with mammary carcinoma without compromising Dox's antitumor potential. Mammary carcinoma was induced in female rats by intraperitonial administration of N-methyl-N-nitrosourea (i.p.). Rats that developed mammary carcinoma were treated with Dox after pretreatment with vehicle or rutin. After Dox exposure (50 days), episodic and spatial memory was assessed using the novel object recognition task and the Morris water maze, respectively. Tumor progression was evaluated by measurement of tumor weight and volume and histological analysis. Blood samples were collected to estimate hematological parameters. Oxidative status and TNF-α levels were estimated in brain homogenates. Dox treatment significantly reduced tumor size and volume. Pretreatment with rutin did not significantly alter Dox's tumor suppression potential, suggesting that it does not influence Dox's anticancer activity. In addition, rutin ameliorated Dox-induced cognitive decline, myelosuppression, and brain oxidative stress. The present study indicates that rutin protects against Dox-induced cognitive decline and myelosuppression without affecting its antitumor potential.

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