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棕榈酸视黄醇酯对肿瘤和正常细胞的抗肿瘤药物毒性损伤的作用。

Retinol palmitate against toxicogenic damages of antineoplastic drugs on normal and tumor cells.

机构信息

Laboratory for Toxicological Genetics, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil.

University Center for Health, Human and Technological Sciences of Piauí, Integrated Health Clinic, UNINOVAFAPI, Teresina, Brazil.

出版信息

Chem Biol Interact. 2020 Oct 1;330:109219. doi: 10.1016/j.cbi.2020.109219. Epub 2020 Aug 23.

Abstract

The lack of tissue selectivity of anticancer drugs generates intense collateral and adverse effects of cancer patients, making the incorporation of vitamins or micronutrients into the diet of individuals to reduce side or adverse effects of antineoplastics. The study aimed to evaluate the effects of retinol palmitate (RP) on the toxicogenic damages induced by cyclophosphamide (CPA), doxorubicin (DOX) and its association with the AC protocol (CPA + DOX), in Sarcoma 180 (S-180) tumor cell line, using the micronuclei test with a block of cytokinesis (CBMN); and in non-tumor cells derived from Mus musculus using the comet assay. The results suggest that CPA, DOX and AC protocol induced significant toxicogenic damages (P < 0.05) on the S-180 cells by induction of micronuclei, cytoplasmic bridges, nuclear buds, apoptosis, and cell necrosis, proving their antitumor effects, and significant damage (P < 0.001) to the genetic material of peripheral blood cells of healthy mice, proving the genotoxic potential of these drugs. However, RP modulated the toxicogenic effects of antineoplastic tested both in the CBMN test (P < 0.05), at the concentrations of 1, 10 and 100 IU/mL; as in the comet assay (P < 0.001) at the concentration of 100 IU/kg for the index and frequency of genotoxic damage. The accumulated results suggest that RP reduced the action of antineoplastics in non-tumor cells as well as the cytotoxic, mutagenic, and cell death in neoplastic cells.

摘要

抗癌药物缺乏组织选择性会对癌症患者产生强烈的副作用和不良反应,因此将维生素或微量营养素纳入个体饮食中,以减少抗肿瘤药物的副作用或不良反应。本研究旨在评估视黄醇棕榈酸酯(RP)对环磷酰胺(CPA)、阿霉素(DOX)及其与 AC 方案(CPA+DOX)诱导的肉瘤 180(S-180)肿瘤细胞系毒性损伤的影响,使用有胞质分裂阻断的微核试验(CBMN);以及使用彗星试验在源自 Mus musculus 的非肿瘤细胞中进行。结果表明,CPA、DOX 和 AC 方案通过诱导微核、细胞质桥、核芽、细胞凋亡和细胞坏死,对 S-180 细胞产生显著的毒性损伤(P<0.05),证明了它们的抗肿瘤作用,并且对健康小鼠外周血淋巴细胞的遗传物质造成显著损伤(P<0.001),证明了这些药物的遗传毒性潜力。然而,RP 调节了测试的抗肿瘤药物的毒性作用,无论是在 CBMN 试验中(P<0.05),在 1、10 和 100 IU/mL 浓度下;还是在彗星试验中(P<0.001),在 100 IU/kg 浓度下,对遗传毒性损伤的指标和频率均有影响。累积的结果表明,RP 降低了非肿瘤细胞中抗肿瘤药物的作用,以及肿瘤细胞中的细胞毒性、致突变性和细胞死亡。

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