Oxidative stress induced by emerging halohydroxybenzonitrile disinfection byproducts and their binding interaction with catalase

Abstract

Halohydroxybenzonitriles (HHBNs) were reported to exist in drinking water as an emerging group of nitrogen-containing aromatic disinfection byproducts (DBPs). The involvement of binding energy with catalase (CAT) as one of molecular descriptors in the quantitative structure-activity relationship model for HHBN cytotoxicity supported that oxidative stress is highly possible to be an essential cytotoxicity mechanism for HHBNs, and the disruption of cellular redox homeostasis may be partly attributed to their interactions towards CAT. However, the relevant evidence is lacking as yet. Thus, in this study, typical biomarkers for oxidative stress and damage in HHBN-treated cells were examined, and the binding interactions between HHBN and CAT were explored. Results indicated that upon exposure to 3,5-dibromo-2-hydroxybenzonitrile, the antioxidant system (e.g., CAT, superoxide dismutase, and glutathione) was disrupted, and excessive reactive oxygen species gave rise to oxidative DNA damage, which further resulted in cell apoptosis. Moreover, the binding interaction between CAT and 3,5-dibromo-2-hydroxybenzonitrile could change the structure and activity of CAT, with the formation of complexes primarily dependent on van der Waals forces and hydrogen bonding. A positive correlation was observed between HHBN cytotoxicity and inhibitory potency on the biological function of CAT, and some unidentified iodinated HHBNs warrant special attention in future owing to their potential high cytotoxicity. The above results contribute to a better understanding of the toxic mechanisms of emerging HHBN DBPs.