Cypermethrin triggers oxidative stress, apoptosis, and inflammation in bovine mammary glands by disruption of mitogen-activated protein kinase (MAPK) pathways and calcium homeostasis

Abstract

Cyano-(3-phenoxyphenyl)methyl]3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate (cypermethrin) is a pyrethroid insecticide that is widely used to repel insects, such as cockroaches and ants. In addition to the target insects, its hazards have been outlined for carp; mice; and the nervous, reproductive, and gastrointestinal systems of humans. However, the effects of cypermethrin on the mammary tissue and milk production in dairy cattle remain unknown. Therefore, in the present study, we aimed to elucidate the impact of cypermethrin on dairy cattle using bovine mammary epithelial cells (MAC-T), which play key roles in milk yield and quality maintenance. First, we assessed the effects of cypermethrin on cell viability, proliferation, and cell cycle progression, followed by correlated gene expression analysis. Cypermethrin-treated cells exhibited G₁ phase arrest and an increase in the sub G₁ population. The population of MAC-T cells in both early and late apoptotic phases was increased following cypermethrin exposure. Moreover, cypermethrin caused mitochondrial calcium overload and diminished the mitochondrial membrane potential in MAC-T cells. We also observed the disruption of mitogen-activated protein kinase (MAPK) cascades and eventually, apoptotic cell death and excessive oxidative stress in cypermethrin-exposed MAC-T cells. In addition, cypermethrin affects the transcription levels related to apoptosis and inflammation, which may lead to the development of clinical morbidities, such as mastitis.