N-acetylcysteine prevents cisplatin-induced cognitive impairments in an ovarian cancer rat model

IF 9.1 1区 医学 Q1 ONCOLOGY
Naomi Lomeli , Diana C. Pearre , Javier Lepe , Donovan A. Argueta , Mya A. Arellano , Joni L. Ricks-Oddie , Kalpna Gupta , Daniela A. Bota
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Abstract

Cancer-related cognitive impairment (CRCI) is prevalent among cancer patients. A critical disparity in the CRCI field is that most pre-clinical studies have been conducted on young cancer-free male rodents, although CRCI predominantly affects breast cancer and ovarian cancer women survivors. Since oxidative stress is widely implicated in the development of CRCI, we developed an ovarian cancer xenograft rat model of CRCI in Cr:NIH-RNU female rats to examine whether administration of the antioxidant N-acetylcysteine (NAC) prevents cisplatin-induced CRCI without altering its anti-cancer efficacy. In vitro, delayed treatment with NAC (10 h) following cisplatin treatment in the human ovarian cancer cell line SKOV3.ip1 did not decrease cisplatin's anti-cancer efficacy while mitigating hippocampal dendritic branching damage and neuronal apoptosis. Rats received subcutaneous and intraperitoneal implantation of SKOV3.ip1 cells. Rats received one cisplatin (5 mg/kg) injection every two weeks for a total of four cycles, with or without NAC (250 mg/kg/day), given for five consecutive days during cisplatin treatment. NAC was administered 10 h after cisplatin, based on our in vitro data. Cognitive testing was performed six to seven weeks after treatment cessation. In vivo, cognitive impairments were observed in tumor-bearing rats in the vehicle and cisplatin-treatment groups, while delayed NAC prevented cognitive impairments. Delayed NAC administration did not affect cisplatin-induced tumor volume reduction. Our study supports using NAC to mitigate cisplatin-induced CRCI through the novel development of an ovarian cancer rodent model. This study highlights the importance of developing clinically relevant tumor-bearing models to elucidate the underlying mechanisms associated with CRCI, which will aid in identifying potential therapeutic agents for preventing CRCI.
n-乙酰半胱氨酸在卵巢癌大鼠模型中预防顺铂诱导的认知障碍。
癌症相关认知障碍(CRCI)在癌症患者中普遍存在。CRCI领域的一个关键差异是,大多数临床前研究都是在年轻的无癌雄性啮齿动物身上进行的,尽管CRCI主要影响乳腺癌和卵巢癌的女性幸存者。由于氧化应激与CRCI的发展有广泛的关系,我们在Cr:NIH-RNU雌性大鼠中建立了CRCI卵巢癌异种移植大鼠模型,以研究抗氧化剂n-乙酰半胱氨酸(NAC)是否能预防顺铂诱导的CRCI而不改变其抗癌功效。在体外,顺铂治疗后延迟NAC治疗(10 h)对人卵巢癌细胞系SKOV3的影响。Ip1不降低顺铂的抗癌效果,但可减轻海马树突分支损伤和神经元凋亡。大鼠皮下和腹腔注射SKOV3。ip1细胞。在顺铂治疗期间,大鼠每两周注射一次顺铂(5mg /kg),共4个周期,加或不加NAC (250mg /kg/天),连续5天。根据我们的体外数据,NAC在顺铂后10小时给药。认知测试在治疗停止后6 - 7周进行。在体内,载药组和顺铂治疗组的荷瘤大鼠出现认知障碍,而延迟NAC可预防认知障碍。延迟NAC给药不影响顺铂诱导的肿瘤体积缩小。我们的研究支持使用NAC通过卵巢癌啮齿动物模型的新发展来减轻顺铂诱导的CRCI。本研究强调了开发临床相关肿瘤承载模型的重要性,以阐明与CRCI相关的潜在机制,这将有助于确定预防CRCI的潜在治疗药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cancer letters
Cancer letters 医学-肿瘤学
CiteScore
17.70
自引率
2.10%
发文量
427
审稿时长
15 days
期刊介绍: Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.
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