A dual-responsive ratiometric indicator designed for in vivo monitoring of oxidative stress and antioxidant capacity.
Majun YangWeida ZhuYilin LvBin JiangChenxia JiangXiaobo ZhouGuo LiYuling QinQi WangZiwei ChenLi WuPublished in: Chemical science (2023)
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 H 2 O 2 and NAD(P)H, which are critical indicators of oxidative stress and antioxidant capacity. DQ1 facilitated the colorimetric and fluorescence detection of H 2 O 2 and NAD(P)H in two well-separated channels, exhibiting a detection limit of 1.0 μM for H 2 O 2 and 0.21 nM for NAD(P)H, respectively. Experiments conducted on living cells and zebrafish demonstrated that DQ1 could effectively detect changes in H 2 O 2 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 H 2 O 2 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.
Keyphrases
- oxidative stress
- induced apoptosis
- living cells
- dna damage
- diabetic rats
- single cell
- fluorescent probe
- ischemia reperfusion injury
- left ventricular
- acute myocardial infarction
- randomized controlled trial
- type diabetes
- systematic review
- high resolution
- single molecule
- mouse model
- rna seq
- risk assessment
- young adults
- endoplasmic reticulum stress
- high throughput
- sensitive detection
- autism spectrum disorder
- papillary thyroid
- cancer therapy
- photodynamic therapy
- intellectual disability
- stem cells
- drug delivery
- skeletal muscle
- label free
- mass spectrometry
- stress induced
- climate change
- acute coronary syndrome
- cell cycle arrest
- cell proliferation
- pi k akt