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

G. V. Ramalingayya, Karthik Gourishetti, Pawan G. Nayak, C. Mallikarjuna Rao, Anoop Kishore, Sulaiman M. Alnaseer, Shalam M. Hussain, Krishnadas Nandakumar

Research output: Contribution to journalArticle

Abstract

Chemobrain is a significant post-chemotherapy complication for which no approved treatments are avail-able. 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-ni-trosourea (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 an-ticancer 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.

Original languageEnglish
Pages (from-to)153-163
Number of pages11
JournalJournal of Environmental Pathology, Toxicology and Oncology
Volume38
Issue number2
DOIs
Publication statusPublished - 01-01-2019

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Toxicology
  • Health, Toxicology and Mutagenesis

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