Linalool reverses benzene-induced cytotoxicity, oxidative stress and lysosomal/mitochondrial damages in human lymphocytes

Abstract

Benzene exposure results in bone marrow suppression, leading to a decrease in the number of circulating white blood cells, an increased risk of chronic lymphocytic leukemia, acute myeloid leukemia and aplastic anemia. Since the mechanism of induction of benzene toxicity is due to active metabolites through cytochrome p450 enzymes and production of reactive oxygen species (ROS), we hypothesized that natural compound such linalool with anti-inflammatory/antioxidant properties could be effective in reducing its toxicity. Lymphocytes isolated from healthy individuals were simultaneously cotreated with different concentrations of LIN (10, 25 and 50 µM) and benzene (50 µM) for 4 h at 37 °C. After incubation, the toxicity parameters such cytotoxicity, ROS formation, lysosomal membrane integrity, mitochondria membrane potential (ΔΨm) collapse, oxidized/reduced glutathione (GSH/GSSG) and malondialdehyde (MDA) were analyzed using biochemical and flow cytometry evaluations. Our data showed that benzene (50 µM) induced a significant increase in cytotoxicity, ROS formation, mitochondrial membrane potential (MMP) collapse, lipid peroxidation and oxidative stress while LIN with antioxidant potential reversed the toxic effects of benzene on isolated human lymphocytes. Our results suggest that LIN reduces and reverses benzene-induced cytotoxicity, oxidative stress and lysosomal/mitochondrial damages in human lymphocyte. This study demonstrated that cotreatment of LIN with benzene can reduce several parameters indicative of oxidative stress. As such, LIN could represent a potential therapeutic agent in reducing certain aspects of benzene-induced toxicity.

Keywords:

• Benzene
• cytotoxicity
• human lymphocytes
• oxidative stress linalool

Acknowledgement

The data presented in the current article were extracted from the Pharm D. thesis of Dr. Farzad Khodaparast. The thesis was conducted under supervision of Dr. Ahmad Salimi at Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences.

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

This study was supported by Ardabil of Medical Sciences, Deputy of Research with ethics code IR.ARUMS.REC.1399.109.