Pyridoxine deficiency modulates benzene inhalation-induced hematotoxicity associated with hepatic CYP2E1 activity in B6C3F1 mice

Chanthana Tangjarukij; Daam Settachan; Judith T Zelikoff; Panida Navasumrit; Mathuros Ruchirawat

doi:10.1016/j.toxrep.2021.08.008

Pyridoxine deficiency modulates benzene inhalation-induced hematotoxicity associated with hepatic CYP2E1 activity in B₆C₃F₁ mice

Toxicol Rep. 2021 Aug 30:8:1607-1615. doi: 10.1016/j.toxrep.2021.08.008. eCollection 2021.

Authors

Chanthana Tangjarukij¹, Daam Settachan^{1

2}, Judith T Zelikoff³, Panida Navasumrit^{1

2}, Mathuros Ruchirawat^{1

2}

Affiliations

¹ Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok, Thailand.
² Center of Excellence on Environmental Health and Toxicology (EHT), Bangkok, 10400, Thailand.
³ Department of Environmental Medicine, New York University School of Medicine, New York, USA.

Abstract

Pyridoxine is a co-factor in many enzymatic reactions and impacts of deficiency have been observed in affected populations. A possible modifying effect of pyridoxine deficiency on benzene toxicity was assessed in male B₆C₃F₁ mice fed either a pyridoxine-deficient diet or a control diet. This treatment was combined with benzene inhalation exposure (100 ppm) or no benzene treatment. Pyridoxine-deficient mice exposed to 100 ppm benzene had significantly lower body, thymus and spleen weights. While total white blood cell counts, percentage of lymphocytes, hematocrit and hemoglobin levels were lower, the percentage of neutrophils was significantly higher in deficient and benzene-exposed mice compared to non-exposed controls. Hepatic CYP2E1 protein expression and activity in the deficient and exposed mice were also significantly higher compared to the non-exposed controls. A significant correlation between CYP2E1 activity and several hematological parameters was observed. These results demonstrated that pyridoxine deficiency significantly impacted benzene-induced hematotoxicity. Moreover, the observed agonistic effect of pyridoxinedeficiency and benzene inhalation exposure on CYP2E1 would seem to indicate an involvement of metabolism, but this needs to be further assessed.

Keywords: Benzene inhalation; Hematotoxicity; Hepatic CYP2E1; Pyridoxine deficiency.