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抗氧化防御对奥美拉唑诱导的瑞士小鼠毒理学作用的影响。

Antioxidative defense against omeprazole-induced toxicogenetical effects in Swiss mice.

机构信息

Laboratory of Genetics and Toxicology (LAPGENIC), Federal University of Piauí, 64.049-550, Teresina, Piauí, Brazil.

Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, 64.049-550, Teresina, Piauí, Brazil.

出版信息

Pharmacol Rep. 2021 Apr;73(2):551-562. doi: 10.1007/s43440-021-00219-1. Epub 2021 Jan 21.

Abstract

BACKGROUND

Omeprazole (OME), a most frequently used proton pump inhibitor in gastric acidosis, is evident to show many adverse effects, including genetic instability. This study evaluated toxicogenic effects of OME in Mus musculus.

METHODS

For this study, 40 male Swiss mice were divided into 8 groups (n = 5) and treated with OME at doses of 10, 20, and 40 mg/kg and/or treated with the antioxidants retinol palmitate (100 IU/kg) and ascorbic acid (2.0 μM/kg). Cyclophosphamide 50 mg/kg, (cytotoxic agent) and the vehicle were served as positive and negative control group, respectively. After 14 days of treatment, the stomach cells along with the bone marrow and peripheral blood lymphocytes were collected and submitted to the comet assay (alkaline version) and micronucleus test. Additionally, hematological and biochemical parameters of the animals were also determined inspect of vehicle group.

RESULTS

The results suggest that OME at all doses induced genotoxicity and mutagenicity in the treated cells. However, in association with the antioxidants, these effects were modulated and/or inhibited along with a DNA repair capacity.

CONCLUSIONS

Taken together, antioxidants (such as retinol palmitate and ascorbic acid) may be one of the best options to counteract OME-induced cytogenetic instability.

摘要

背景

奥美拉唑(OME)是治疗胃酸过多最常用的质子泵抑制剂,其已被证实具有多种不良反应,包括遗传不稳定性。本研究评估了 OME 对 Mus musculus 的毒性作用。

方法

本研究将 40 只雄性瑞士小鼠分为 8 组(n = 5),分别用 OME 10、20 和 40mg/kg 剂量处理和/或用抗氧化剂视黄醇棕榈酸酯(100IU/kg)和抗坏血酸(2.0μM/kg)处理。环磷酰胺 50mg/kg(细胞毒性剂)和载体分别作为阳性和阴性对照组。治疗 14 天后,收集胃细胞以及骨髓和外周血淋巴细胞,并进行彗星试验(碱性版)和微核试验。此外,还检测了动物的血液学和生化参数,而不考虑载体组。

结果

结果表明,OME 在所有剂量下均诱导了处理细胞的遗传毒性和致突变性。然而,与抗氧化剂联合使用时,这些效应被调节和/或抑制,同时伴随着 DNA 修复能力的增强。

结论

综上所述,抗氧化剂(如视黄醇棕榈酸酯和抗坏血酸)可能是对抗 OME 诱导的细胞遗传不稳定性的最佳选择之一。

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