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.

中文翻译：

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芦丁在保持N-甲基-N-亚硝基脲-诱导的乳腺癌的小鼠模型中保留Dox的抗癌潜力的同时，还可以预防阿霉素诱导的认知功能障碍。

Chemobrain是严重的化疗后并发症，目前尚无批准的治疗方法。我们先前已经发现芦丁可以抑制阿霉素（Dox-）诱导的健康大鼠认知能力下降。但是，重要的是要确定在不损害Dox的抗肿瘤潜力的情况下在患有乳癌的大鼠中这样做。通过腹膜内施用N-甲基-N-亚硝基脲（ip）在雌性大鼠中诱发乳癌。在用赋形剂或芦丁预处理后，用Dox治疗发生乳癌的大鼠。暴露于Dox后（50天），分别使用新颖的物体识别任务和Morris水迷宫评估了情景记忆和空间记忆。通过测量肿瘤的重量和体积以及组织学分析评估肿瘤的进展。收集血液样本以估计血液学参数。估计脑匀浆中的氧化状态和TNF-α水平。Dox治疗显着降低了肿瘤的大小和体积。芦丁预处理并未显着改变Dox的抑瘤潜力，这表明它不影响Dox的抗癌活性。此外，芦丁改善了Dox引起的认知能力下降，骨髓抑制和脑部氧化应激。本研究表明，芦丁可预防Dox引起的认知功能下降和骨髓抑制，而不会影响其抗肿瘤潜力。具有抑制肿瘤的潜力，表明它不影响Dox的抗癌活性。此外，芦丁改善了Dox引起的认知能力下降，骨髓抑制和脑部氧化应激。本研究表明，芦丁可预防Dox引起的认知功能下降和骨髓抑制，而不会影响其抗肿瘤潜力。具有抑制肿瘤的潜力，表明它不影响Dox的抗癌活性。此外，芦丁改善了Dox引起的认知能力下降，骨髓抑制和脑部氧化应激。本研究表明，芦丁可预防Dox引起的认知能力下降和骨髓抑制，而不会影响其抗肿瘤潜力。