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奥美拉唑的药理作用及毒效遗传学影响:基因组不稳定性与癌症。

Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer.

机构信息

Postgraduate Program in Biotechnology (RENORBIO), Federal University of Piauí, Teresina, PI, Brazil.

Laboratory of Genetic Toxicity, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, PI, Brazil.

出版信息

Oxid Med Cell Longev. 2020 Mar 28;2020:3457890. doi: 10.1155/2020/3457890. eCollection 2020.

Abstract

Omeprazole (OME) is commonly used to treat gastrointestinal disorders. However, long-term use of OME can increase the risk of gastric cancer. We aimed to characterize the pharmacological effects of OME and to correlate its adverse effects and toxicogenetic risks to the genomic instability mechanisms and cancer-based on database reports. Thus, a search (till Aug 2019) was made in the PubMed, Scopus, and ScienceDirect with relevant keywords. Based on the study objective, we included 80 clinical reports, forty-six , and 76 studies. While controversial, the findings suggest that long-term use of OME (5 to 40 mg/kg) can induce genomic instability. On the other hand, OME-mediated protective effects are well reported and related to proton pump blockade and anti-inflammatory activity through an increase in gastric flow, anti-inflammatory markers (COX-2 and interleukins) and antiapoptotic markers (caspases and BCL-2), glycoprotein expression, and neutrophil infiltration reduction. The reported adverse and toxic effects, especially in clinical studies, were atrophic gastritis, cobalamin deficiencies, homeostasis disorders, polyp development, hepatotoxicity, cytotoxicity, and genotoxicity. This study highlights that OME may induce genomic instability and increase the risk of certain types of cancer. Therefore, adequate precautions should be taken, especially in its long-term therapeutic strategies and self-medication practices.

摘要

奥美拉唑(OME)常用于治疗胃肠道疾病。然而,长期使用 OME 会增加胃癌的风险。我们旨在描述 OME 的药理作用,并将其不良反应和毒代动力学风险与基于数据库报告的基因组不稳定性机制和癌症相关联。因此,我们在 PubMed、Scopus 和 ScienceDirect 数据库中使用相关关键字进行了截至 2019 年 8 月的搜索。根据研究目的,我们纳入了 80 项临床报告、46 项和 76 项研究。虽然存在争议,但研究结果表明,长期使用 OME(5 至 40mg/kg)会导致基因组不稳定。另一方面,OME 介导的保护作用得到了很好的报道,其与质子泵阻断和通过增加胃流、抗炎标志物(COX-2 和白细胞介素)和抗凋亡标志物(半胱天冬酶和 BCL-2)、糖蛋白表达和减少中性粒细胞浸润来发挥抗炎活性有关。报道的不良反应和毒性作用,特别是在临床研究中,有萎缩性胃炎、钴胺素缺乏、内稳态紊乱、息肉发育、肝毒性、细胞毒性和遗传毒性。本研究强调,OME 可能会诱导基因组不稳定性,并增加某些类型癌症的风险。因此,应采取充分的预防措施,特别是在其长期治疗策略和自我用药实践中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a156/7146093/36f8808bdf7d/OMCL2020-3457890.001.jpg

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