Bone Marrow Injury Induced via Oxidative Stress in Mice by Inhalation Exposure to Formaldehyde

Yuchao Zhang,Yang Wu,Xu Yang,Luoping Zhang,Cliona Mchale,Rui Li,Xin Ye,Shumao Ding,Xudong Liu,Rajesh Mohanraj

doi:10.1371/journal.pone.0074974

Yuchao Zhang, Yang Wu + Show 8 more

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https://doi.org/10.1371/journal.pone.0074974

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Abstract

ObjectiveFormaldehyde, a ubiquitous environmental pollutant has been classified as a human leukemogen. However, toxicity of formaldehyde in bone marrow, the target site of leukemia induction, is still poorly understood.Methodology/Principal FindingsTo investigate bone marrow toxicity (bone marrow pathology, hematotoxicity) and underlying mechanisms (oxidative stress, inflammation, apoptosis) in formaldehyde-exposed mice. Male Balb/c mice were exposed to formaldehyde (0, 0.5, and 3.0 mg/m3) by nose-only inhalation for 8 hours/day, over a two week period designed to simulate a factory work schedule, with an exposure-free “weekend” on days 6 and 7, and were sacrificed on the morning of day 13. Counts of white blood cells, red blood cells and lymphocytes were significantly (p<0.05) decreased at 0.5 mg/m3 (43%, 7%, and 39%, respectively) and 3.0 mg/m3 (52%, 27%, and 43%, respectively) formaldehyde exposure, while platelet counts were significantly increased by 109% (0.5 mg/m3) and 67% (3.0 mg/m3). Biomarkers of oxidative stress (reactive oxygen species, glutathione depletion, cytochrome P450 1A1 and glutathione s-transferase theta 1 expression), inflammation (nuclear factor kappa-B, tomour necrosis factor alpha, interleukin-1 beta), and apoptosis (activity of cysteine-aspartic acid protease 3) in bone marrow tissues were induced at one or both formaldehyde doses mentioned above.Conclusions/SignificanceExposure of mice to formaldehyde by inhalation induced bone marrow toxicity, and that oxidative stress, inflammation and the consequential apoptosis jointly constitute potential mechanisms of such induced toxicity.

Highlights

Formaldehyde (FA) is a ubiquitous chemical that is used in a large number of industrial activities and found in many consumer products [1,2]
The International Agency for Research on Cancer (IARC) [10] and the U.S National Toxicology Program [11] have both classified FA as a human leukemogen based on epidemiological studies that suggest an increased risk of leukemia; the biological plausibility of FA-induced leukemia is controversial [12] because limited information is available on the ability of FA to disrupt hematopoietic function [13] and on mechanisms of leukemia induction
FA has been classified as a human leukemogen by IARC and U.S National Toxicology Program, the biological plausibility of FA-induced leukemia is still controversial

Summary

Introduction

Formaldehyde (FA) is a ubiquitous chemical that is used in a large number of industrial activities and found in many consumer products [1,2]. The International Agency for Research on Cancer (IARC) [10] and the U.S National Toxicology Program [11] have both classified FA as a human leukemogen based on epidemiological studies that suggest an increased risk of leukemia; the biological plausibility of FA-induced leukemia is controversial [12] because limited information is available on the ability of FA to disrupt hematopoietic function [13] and on mechanisms of leukemia induction. Increased levels of oxidative stress can induce inflammation and subsequently cell apoptosis [19]. Induction of oxidative stress, inflammation and apoptosis in BM of animal exposed to FA by inhalation have not been comprehensively measured though one study

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