Mechanisms of Multi-Toxicant Oxidative Stress: Dysregulation of The NF-Κb/Iκb Axis By Ozone, 4-(N-Methyl-N-Nitrosamino)-1-(3-Pyridyl)-1-Butanone (NNK) and/or Dibutyl Phthalate (DBP)

Abstract

ABSTRACT This study explores the NF-κB-mediated oxidative stress pathways in B6C3F1 mouse lungs and livers following 16- and 32-week exposures to ozone, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and/or dibutyl phthalate (DBP). EMSA and Western blot analyses revealed that while lung NF-κB activation was strictly toxicant-induced across all exposure groups, hepatic responses varied-showing distinct activation by single and dual treatments but attenuated activity in the 16-week triple-exposure cohort. Additionally, toxicant exposure consistently upregulated NF-κB subunits (p105, p65, and p50) and promoted IκB degradation in both tissues at both time points. Collectively, our data demonstrate that chronic exposure to these toxicants profoundly exacerbates oxidative stress through the dysregulation of NF-κB signaling.