A dual-responsive ratiometric indicator designed for in vivo monitoring of oxidative stress and antioxidant capacity

Abstract

The imbalance between oxidative stress and antioxidant capacity is strongly associated with the development of numerous degenerative diseases, including cardiovascular diseases, diabetes, neurodegenerative diseases, and cancer. Therefore, monitoring oxidative stress and antioxidant capacity in vivo is crucial for maintaining cellular homeostasis and the stability of the organism's internal environment. Here, we present the findings of our study on DQ1, a dual-responsive indicator designed specifically for imaging H₂O₂ and NAD(P)H, which are critical indicators of oxidative stress and antioxidant capacity. DQ1 facilitated the colorimetric and fluorescence detection of H₂O₂ and NAD(P)H in two well-separated channels, exhibiting a detection limit of 1.0 μM for H₂O₂ and 0.21 nM for NAD(P)H, respectively. Experiments conducted on living cells and zebrafish demonstrated that DQ1 could effectively detect changes in H₂O₂ and NAD(P)H levels when exposed to exogenous hypoxic conditions and chemical stimuli. Furthermore, the effectiveness of the as-fabricated indicator was investigated in two distinct mouse models: evaluating H₂O₂ and NAD(P)H levels in myocardial cell dysfunction during acute myocardial infarction and liver tissue damage under trichloroethylene stress conditions. In vivo experiments demonstrated that the levels of the two cardiac biomarkers increase progressively with the development of myocardial infarction, eventually reaching a steady state after 7 days when the damaged cells in the infarcted region become depleted. Moreover, during 14 continuous days of exposure to trichloroethylene, the two biomarkers in liver tissue exhibited a sustained increase, indicating a significant enhancement in intracellular oxidative stress and antioxidant capacity attributed to the mouse liver's robust metabolic capacity. The aforementioned studies underscore the efficacy of DQ1 as a valuable tool for scrutinizing redox states at both the single-cell and biological tissue levels. It presents significant potential for investigating the dynamic alternations in oxidative stress and antioxidant capacity within disease models as the disease progresses, thereby facilitating a more profound comprehension of these processes across various disease models.