Amifostine Protects Bone Marrow from Benzene-Induced Hematotoxicity in Mice

Abstract

Benzene is one of the most widely used industrial chemical agents. Long-term benzene exposure causes bone marrow aplasia and leads to a wide range of hematopoietic disorders including aplastic anaemia (AA). There are currently no effective approaches to protect people from benzene-induced hematotoxicity and AA. In addition, current treatments for AA have limitations with short- and long-term risks. Protective agents and new therapeutic approaches, therefore, are needed to prevent and treat the disease. Amifostine is a well-known cytoprotective agent and has been widely used in clinical for protecting normal tissues from the toxic effects of chemotherapy and radiotherapy. The authors utilized an established mouse model to determine the protective effect of amifostine on benzene-induced bone marrow hematotoxicity. Whole-blood cell count, morphological and histopathological alterations in the bone marrow and spleen, as well as the production of inducible toxic oxidative species were examined and compared among the mouse groups. Amifostine treatment in benzene-exposed mice significantly improved blood cell counts, and morphological and histopathological signs of hematotoxicity in the bone marrow as well as in the spleen. Moreover, amifostine prevented benzene-induced bone marrow and spleen cell apoptosis and rescinded the inhibition of cell proliferation induced by benzene exposure. Finally, amifostine significantly inhibited the levels of reactive oxidative species and lipid peroxidation induced by benzene exposure. These data suggest that amifostine appears to have substantial protective effect on benzene-induced bone marrow hematotoxicity.

Benzene induces haematotoxicity by promoting deacetylation and autophagy

“…Silencing of ATG5, but not Z‐VAD‐fmk, significantly inhibited HQ‐induced cell death, further confirming that low concentrations of HQ induce autophagic cell death but not apoptosis in BMMNCs. In benzene‐induced haematotoxicity mouse model, treatment with 1 mL/kg benzene for 4 weeks only promoted autophagy but not apoptosis, inconsistently with our previous study, in which treatment with 2 mL/kg benzene for 8 weeks promoted a marked apoptosis in BMMNCs.…”

“…Blood cell counts were assessed as described previously . Briefly, the level of haemoglobin was determined using a haemoglobin analyser (Mission, Sichuan, China).…”

“…It has been suggested that benzene metabolites can cause damage to haematopoietic cells via multiple mechanisms such as chromosomal aberration and covalent binding, epigenetic regulation, oxidative stress, and disruption of tumour surveillance . We have also shown that exposure to high‐dose benzene or its metabolite hydroquinone (HQ) leads to haematopoietic toxicity through induction of apoptosis in vivo and in vitro . However, it remains unknown how low concentration of benzene exposure also results in haematopoietic toxicity.…”

Gender-linked haematopoietic and metabolic disturbances induced by a pesticide mixture administered at low dose to mice

“…These cancers are characterized by genetic anomalies that affect the proliferation, survival and differentiation of haematopoietic progenitors or haematopoietic stem cells (Gilliland, 2002;Kelly and Gilliland, 2002;Gilliland et al, 2004). Besides the etiological factors identified as being involved in the initiation and development of diseases such as immunodeficiency (Grulich and Vajdic, 2005), viral infections , and genetic disorders (Rudant et al, 2007;Wang et al, 2007), environmental factors are believed to play a key role in the development of malignant haemopathies (Descatha et al, 2005;Yu et al, 2007).…”

Involvement of hypoxia-inducible factor-1 α (HIF-1α) in inhibition of benzene on mouse hematopoietic system

“…Chronic exposure to benzene leads to aplastic anemia and damage to BM and a wide range of hematopoietic disorders (Santiago et al, 2014;Yu et al, 2007). In our study, mice in the benzene groups displayed weight loss.…”