Influence of bifentrin, a pyrethriod pesticide, on human colorectal HCT-116 cells attributed to alterations in oxidative stress involving mitochondrial apoptotic processes

ABSTRACT

The widespread use of pesticides is beneficial for food production; however, there are numerous adverse consequences reported in the ecosystem and humans associated with exposure to these contaminants. The pyrethriod bifenthrin (BIF) is utilized for (1) maintenance, growth, and storage of agricultural products; (2) control of internal and external parasites of farm animals; and (3) eradication of insects threatening public health. Numerous data are available regarding environmental and ecological impact of pyrethriods on the central and peripheral nervous systems; however few studies focused on non-target tissues especially in humans. Therefore, the aim of this investigation was to determine the potential cytotoxic effects of BIF on a non-target tissue using human colorectal HCT-116 cells as a model. Data demonstrated that BIF reduced cell viability and disrupted mitochondrial functions which were accompanied by increased reactive oxygen species (ROS) levels indicating the presence of oxidative stress. BIF produced a significant elevation in levels of malondialdehyde (MDA) supporting the role of oxidative stress in pesticide-mediated toxicity. Concomitantly, a fall of mitochondrial transmembrane potential (Δψ), consequently producing perturbation of fluidity as well as excitability of cellular membranes was noted. Our results also indicated that BIF induced a rise in DNA damage as evidenced by the comet assay. An increase in mitogen-activated protein kinases (MAPKs), JNK (N-terminal Kinase), p38, and ERK (extracellular-signal-regulated kinase) suggested an apoptotic effect. Data thus indicated that BIF-induced cytotoxicity in human colorectal HCT-116 cells was associated with oxidative stress, mitochondrial dysfunction, and apoptosis.

GRAPHICAL ABSTRACT

Cytotoxic pathway of Bifenthrin in HCT116 cells

Bifenthrin induces cell membranes destabilization leading to the recruitment of three Mitogen-Activated Protein Kinases (MAPKs) and the activation of the mitochondrial apoptotic pathway.

KEYWORDS:

• Bifenthrin
• oxidative stress
• DNA damage
• mitogen-activated protein kinases (MAPKs)
• apoptosis

Acknowledgments

This study was supported by “Le Ministère Tunisien de l’Enseignement Supérieur, de la Recherche Scientifique et de la Technologie.