Evaluating the effects of anticoagulant rodenticide bromadiolone in Wistar rats co-exposed to vitamin K: impact on blood-liver axis and brain oxidative status

Mol Cell Biochem. 2022 Feb;477(2):525-536. doi: 10.1007/s11010-021-04303-1. Epub 2021 Nov 23.

Abstract

The aim of this study was to investigate the beneficial effects of vitamin K relate to protection against detrimental effects of bromadiolone. Wistar rats (n = 30) were divided in three groups (n = 10): control group and two groups treated with bromadiolone (0.12 mg/kg) and bromadiolone + vitamin K (0.12 mg/kg + 100 mg/kg) over the period of four days. The main findings in the bromadiolone-exposed rats, such as damaged hepatocytes, high levels of globulin, total proteins and lymphocytes, and altered albumin/globulin ratio, collectively indicate an acute inflammatory process. Morphological changes in erythrocytes include microcytosis, hypochromia, hyperchromia, hemolysis, stomatocytosis, and spherocytosis. Significantly low values of RBC, Hct, and hemoglobin concentrations indicate impairments of the hematopoietic pathway causing combined anemia. The selected dose of bromadiolone caused a non-significant increase of catalase activity and a significant increase of the total protein content in brain tissue homogenates. Vitamin K supplementation reduced many of the harmful effects of bromadiolone. The cytoprotective role of vitamin K was proved to be of great importance for the preservation of structural changes on the membranes of hepatocytes and erythrocytes, in addition to the known role in the treatment of coagulopathies. The results of the study suggest valuable properties of vitamin K in the prevention and treatment of various types of anemia caused by bromadiolone toxicity. Future research is necessary to determine the adequate dose and treatment duration with vitamin K in disorders caused by the cumulative action of bromadiolone and possibly other pesticides.

Keywords: Bromadiolone; Hyperglobulinemia; Spherocytosis; Stomatocytosis; Vitamin K.

MeSH terms

  • 4-Hydroxycoumarins* / pharmacokinetics
  • 4-Hydroxycoumarins* / pharmacology
  • Animals
  • Anticoagulants* / pharmacokinetics
  • Anticoagulants* / pharmacology
  • Brain / metabolism*
  • Drug Evaluation, Preclinical
  • Liver / metabolism*
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Rodenticides* / pharmacokinetics
  • Rodenticides* / pharmacology
  • Vitamin K* / pharmacokinetics
  • Vitamin K* / pharmacology

Substances

  • 4-Hydroxycoumarins
  • Anticoagulants
  • Rodenticides
  • Vitamin K
  • bromadiolone