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与抗坏血酸 - 顺铂联合治疗效果及对荷瘤小鼠顺铂诱导毒性的保护作用相关的生化变化。

Biochemical changes associated with ascorbic acid-cisplatin combination therapeutic efficacy and protective effect on cisplatin-induced toxicity in tumor-bearing mice.

作者信息

Longchar Amenla, Prasad Surya Bali

机构信息

Cell and Tumor Biology Laboratory, Department of Zoology, North-Eastern Hill University, Shillong 793 022, India.

出版信息

Toxicol Rep. 2015 Feb 7;2:489-503. doi: 10.1016/j.toxrep.2015.01.017. eCollection 2015.

Abstract

Cisplatin is one of the well-established anticancer drugs being used against a wide spectrum of cancers. However, full therapeutic efficacy of the drug is limited due to development of various toxicities in the host. This study examines the comparative therapeutic effectiveness and toxicities of cisplatin alone and in combination of dietary ascorbic acid (AA) in ascites Dalton's lymphoma-bearing mice. The findings show that the combination treatment of mice with ascorbic acid plus cisplatin has much better therapeutic efficacy against murine ascites Dalton's lymphoma (DL) in comparison to cisplatin alone and this may involve a decrease in reduced glutathione (GSH), catalase activity and increased lipid peroxidation (LPO) in Dalton's lymphoma tumor cells. At the same time, combination treatment indicates a protective role of ascorbic acid against cisplatin-induced tissue toxicities (side effects) in the hosts. Cisplatin-induced histopathological changes in liver, kidney and testes were decreased after combination treatment. The analysis of renal function test (RFT), liver function test (LFT) and sperm abnormalities also suggest an improvement in these parameters after combination treatment. Therefore, it may be concluded that the increased GSH level, catalase activity and decreased LPO in the tissues, ., liver, kidney and testes after combination treatment may be involved in its protective ability against cisplatin-induced tissue toxicities in the host.

摘要

顺铂是一种广泛应用于多种癌症治疗的成熟抗癌药物。然而,由于宿主出现各种毒性反应,该药物的完全治疗效果受到限制。本研究考察了顺铂单独使用以及与膳食抗坏血酸(AA)联合使用对荷腹水型道尔顿淋巴瘤小鼠的相对治疗效果和毒性。研究结果表明,与单独使用顺铂相比,抗坏血酸加顺铂联合治疗对小鼠腹水型道尔顿淋巴瘤(DL)具有更好的治疗效果,这可能与道尔顿淋巴瘤肿瘤细胞中还原型谷胱甘肽(GSH)减少、过氧化氢酶活性降低以及脂质过氧化(LPO)增加有关。同时,联合治疗表明抗坏血酸对顺铂诱导的宿主组织毒性(副作用)具有保护作用。联合治疗后,顺铂诱导的肝脏、肾脏和睾丸组织病理学变化有所减轻。肾功能试验(RFT)、肝功能试验(LFT)分析以及精子异常情况也表明联合治疗后这些参数有所改善。因此,可以得出结论,联合治疗后组织(即肝脏、肾脏和睾丸)中GSH水平升高、过氧化氢酶活性增强以及LPO降低,可能与其对宿主顺铂诱导的组织毒性的保护能力有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1122/5598450/0707c24bb5f8/gr1.jpg

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