Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer.
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Paz Márcia Fernanda Correia Jardim, de Alencar Marcus Vinícius Oliveira Barros, de Lima Rodrigo Maciel Paulino, Sobral André Luiz Pinho, do Nascimento Glauto Tuquarre Melo, Dos Reis Cristiane Amaral, Coêlho Maria do Perpetuo Socorro de Sousa, do Nascimento Maria Luísa Lima Barreto, Gomes Júnior Antonio Luiz, Machado Kátia da Conceição, de Menezes Ag-Anne Pereira Melo, de Lima Rosália Maria Torres, de Oliveira Filho José Williams Gomes, Dias Ana Carolina Soares, Dos Reis Antonielly Campinho, da Mata Ana Maria Oliveira Ferreira, Machado Sônia Alves, Sousa Carlos Dimas de Carvalho, da Silva Felipe Cavalcanti Carneiro, Islam Muhammad Torequl, de Castro E Sousa João Marcelo, Melo Cavalcante Ana Amélia de Carvalho
Аннотация
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 in vitro, and 76 in vivo 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.