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

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.

Graphical abstract

Fig. 1

The effects of pyridoxine deficiency and benzene inhalation exposure (0 or 100 ppm) on white blood cell counts, percentages of neutrophils, lymphocytes and eosinophils, hematocrit and hemoglobin. Values are expressed as mean ± SE (n = 10/group). ^{a, b} Significantly different from CD-0 controls at ^ap < 0.05 and ^bp < 0.001, respectively. ^c Significantly different from benzene-matched CD-100 group at p < 0.001. ^{d, e} Significantly different from PD-0 controls at ^dp < 0.05 and ^ep < 0.001, respectively.

Fig. 2

The effects of pyridoxine deficiency and benzene inhalation exposure (0 or 100 ppm) on hepatic CYP2E1 protein expression and CYP2E1 activity (mean ± SE, n = 10/group). Panel A: The level of CYP2E1 expression was measured as the intensity of protein bands, while that of the controls (CD-0) was arbitrarily assigned a value of 100 % and the intensities of the protein bands in other lanes were expressed relative to that of the CD-0 controls samples using densitometry. Panel B: The effects of pyridoxine deficiency and benzene inhalation exposure (0 or 100 ppm) on hepatic CYP2E1 activity. ^{a, b} Significantly different from CD-0 controls at ^ap < 0.05 and ^bp < 0.001, respectively. ^c Significantly different from PD-0 controls at p < 0.05.