Application of the in vivo oxidative stress reporter Hmox1 as mechanistic biomarker of arsenic toxicity

Inorganic arsenic (iAs) is a naturally occurring metalloid present in drinking water and polluted air exposing millions of people globally. Epidemiological studies have linked iAs exposure to the development numerous diseases including cognitive impairment, cardiovascular failure cancer. Despite intense research, an effective therapy for chronic arsenicosis has yet be developed. Laboratory been great benefit establishing pathways involved toxicity providing insights into its mechanism action. However, vivo analysis mechanisms difficult by lack reliable biomarkers iAs’s effects. To address this issue we applied use our recently developed stress reporter models study toxicity. The mice Hmox1 (oxidative stress/inflammation; HOTT) p21 (DNA damage) were exposed at acute chronic, environmentally relevant, doses. We observed induction oxidative reporters several cell types tissues, which was largely dependent on activation transcription factor NRF2. propose that HOTT model can used as surrogate biomarker iAs-induced stress, it constitutes first-in-class platform develop treatments aimed counteract role arsenicosis. Indeed, proof concept experiment, able predict therapeutic utility antioxidant N-acetyl cysteine prevention associated