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

Ramalingayya, GV and Gourishetti, Karthik and Nayak, Pawan G and Rao, Mallikarjuna C and Kishore, Anoop and Nandakumar, Krishnadas (2019) 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. Journal of Environmental Pathology, Toxicology and Oncology, 38 (2). pp. 153-163. ISSN 0731-8898

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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

Item Type: Article
Uncontrolled Keywords: Chemobrain; Rutin; Doxorubicin; Cognitive dysfunction; Novel object recognition task; Memory
Subjects: Pharmacy > MCOPS Manipal > Pharmacology
Depositing User: KMC Library
Date Deposited: 31 Jul 2019 04:02
Last Modified: 31 Jul 2019 04:02
URI: http://eprints.manipal.edu/id/eprint/154177

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