Evaluating an In Vivo Oxidative Stress sensor in cystic fibrosis rat epithelial tissues

Abstract

We have developed a novel biosensing device that can detect the real-time, dynamic state of in vivo oxidative status (IVOS) in living systems. Oxidative stress is a well-established condition in CF animal models and humans. Elevated oxidative stress conditions are associated with excessive inflammatory responses from neutrophils that result in fibrotic tissue formation. As such, numerous clinical and preclinical studies suggest that elevated oxidative stress, combined with the heightened pro-inflammatory milieu observed in CF phenotypes, likely increases susceptibility to recurrent infection-inflammation cycles. We aimed to use the IVOS sensor to characterise oxidative environmental differences in wildtype, CF Phe508del and CFTR knockout rat epithelial tissues including the lungs, trachea, nasal mucosa, and oesophagus. Our results revealed no significant differences in the baseline redox balance between wildtype, Phe508del and knockout rat tissues, however when we looked at short term fluctuations in redox status using the ratio of the root mean squared of successive differences (RMSSD) to the normalised mean IVOS arbitrary units, we saw significantly elevated fluctuations in the redox status in the bronchi of Phe508del rats compared to wildtype rats, indicating a lower steady-state oxidative environment combined with large transient oxidative events.