Antioxidative defense against omeprazole-induced toxicogenetical effects in Swiss mice

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.

Keywords: Antioxidants; Genotoxicity; Mus musculus; Mutagenicity; Omeprazole.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antioxidants / pharmacology*
  • Ascorbic Acid / pharmacology*
  • Comet Assay
  • Cyclophosphamide / toxicity
  • DNA Repair / drug effects
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Mutagenesis / drug effects
  • Omeprazole / administration & dosage
  • Omeprazole / toxicity*
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / toxicity
  • Retinyl Esters / pharmacology*

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Diterpenes
  • Proton Pump Inhibitors
  • Retinyl Esters
  • retinol palmitate
  • Cyclophosphamide
  • Omeprazole
  • Ascorbic Acid