Benzene Exposure Alters Expression of Enzymes Involved in Fatty Acid β-Oxidation in Male C3H/He Mice

Abstract

Abstract:Benzene is a well-known hematotoxic carcinogen that can cause leukemia and a variety of blood disorders. Our previous study indicated that benzene disturbs levels of metabolites in the fatty acid β-oxidation (FAO) pathway, which is crucial for the maintenance and function of hematopoietic and leukemic cells. The present research aims to investigate the effects of benzene on changes in the expression of key enzymes in the FAO pathway in male C3H/He mice. Results showed that benzene exposure caused reduced peripheral white blood cell (WBC), red blood cell (RBC), platelet (Pit) counts, and hemoglobin (Hgb) concentration. Investigation of the effects of benzene on the expression of FA transport-and β-oxidation-related enzymes showed that expression of proteins Cpt1a, Crat, Acaa2, Aldh1l2, Acadvl, Crot, Echs1, and Hadha was significantly increased. The ATP levels and mitochondrial membrane potential decreased in mice exposed to benzene. Meanwhile, reactive oxygen species (ROS), hydrogen peroxide (H 2 O 2 ), and malondialdehyde (MDA) levels were significantly increased in the benzene group. Our results indicate that benzene induces increased expression of FA transport and β-oxidation enzymes, mitochondrial dysfunction, and oxidative stress, which may play a role in benzene-induced hematotoxicity.

Bone Marrow Oxidative Stress and Acquired Lineage-Specific Genotoxicity in Hematopoietic Stem/Progenitor Cells Exposed to 1,4-Benzoquinone

“…In addition to lipids, free radicals can also react with proteins with protein carbonyl (PC) production, which are among the established biomarkers to indicate protein oxidation [ 36 , 37 ]. In this study, we detected an increase in PC levels in 1,4-BQ treated groups as compared with the untreated control group.…”

“…Physiologically, oxidative stress is a result of increased ROS and/or reactive nitrogen species (RNS) and impaired activities of antioxidant defence enzymes [ 35 , 36 ]. There is growing evidence that benzene metabolism involves redox cycling producing reactive oxygen species (ROS), leading to reduced gluthathione (GSH) and causing further oxidative stress in bone marrow cells [ 37 , 38 , 39 ].…”

l‐Carnitine protects against 1,4‐benzoquinone‐induced apoptosis and DNA damage by suppressing oxidative stress and promoting fatty acid oxidation in K562 cells

“…In our previous study, we found that benzene exposure‐induced alterations in several metabolites and key genes in the FAO pathway in mice 10 . Additionally, administration of acetyl‐LC to mice reduced oxidative damage and hematopoietic toxicity caused by benzene exposure 11 .…”

“…Studies have shown that increased levels of reactive oxygen species (ROS) are produced during benzene metabolism and when cells are exposed to benzene or its metabolites 8,9 . Elevated ROS then induces oxidative stress, leading to damage to many biological macromolecules such as lipids, proteins, and DNA 9‐11 . Many in vivo and in vitro studies have suggested that benzene and its metabolites can cause DNA damage 12,13 .…”

New insights on ‘old’ toxicants in occupational toxicology

“…These results suggest the potential role of benzene in the development of glucose metabolism dysregulations. Even if the study of Bahadar et al (59) examined the molecular effects of benzene at relatively high doses, similar pathways may be involved in the pathogenesis of chronic cellular damage at other sites (60), even at low degrees of exposure. In this regard, a study of our group enrolled 91 male gas station attendants and compared them to a control population of 63 male office workers (61).…”