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Optical imaging of mitochondrial redox state in rodent models with 3-iodothyronamine
Zahra Ghanian1, Sepideh Maleki, Hannah Reiland
1Biophotonics Laboratory, Department of Electrical Engineering and Computer Science, University of Wisconsin Milwaukee, Milwaukee, WI 53211-3029, USA.
Abstract:
This study used an optical technique to measure the effects of treating low (10 mg/kg) and high (25 mg/kg) doses of 3-iodothyronamine (T₁AM) on the metabolism in the kidney and heart of mice. The ratio of two intrinsic fluorophores in tissue, (NADH/FAD), called the NADH redox ratio (NADH RR), is a marker of the metabolic state of the tissue. A cryofluorescence imaging instrument was used to provide a quantitative assessment of NADH RR in both kidneys and hearts in mice treated with 3-iodothyronamine. We compared those results to corresponding tissues in control mice. In the kidneys of mice treated with a high dose T₁AM, the mean values of the maximum projection of NADH RR were 2.6 ± 0.6 compared to 3.20 ± 0.03 in control mice, indicating a 19% (± 0.4) significant increase in oxidative stress (OS) in the high dose-treated kidneys (P = 0.047). However, kidneys treated with a low dose of T₁AM showed no difference in NADH RR compared to the kidneys of control mice. Furthermore, low versus high dose treatment of T₁AM showed different responses in the heart than in the kidneys. The mean value of the maximum projection of NADH RR in the heart changed from 3.0 ± 0.3 to 3.2 ± 0.6 for the low dose and the high dose T₁AM-treated mice, respectively, as compared to 2.8 ± 0.7 in control mice. These values correspond to a 9% (±0.5) (P = 0.045) and 14% (±0.5) (P = 0.008) significant increase in NADH RR in the T₁AM-treated hearts, indicating that the high dose T₁AM-treated tissues have reduced OS compared to the low dose-treated tissues or the control tissues. These results suggest that while T₁AM at a high dose increases oxidative response in kidneys, it has a protective effect in the heart and may exert its effect through alternative pathways at different doses and at tissue specific levels.
Insights
3-iodothyronamine (T₁AM) affects mouse kidney and heart metabolism differently based on dose. High-dose T₁AM increases oxidative stress in kidneys but protects the heart, suggesting dose- and tissue-specific effects.
Area of Science:
- Biochemistry
- Physiology
- Optical Imaging
Background:
- Metabolic state is crucial for organ function and can be assessed using intrinsic tissue fluorophores.
- The NADH/FAD ratio, or NADH redox ratio (NADH RR), serves as a quantitative marker for cellular metabolic status.
- 3-iodothyronamine (T₁AM) is a thyroid hormone derivative with known metabolic effects, but its tissue-specific impacts require further investigation.
Purpose of the Study:
- To investigate the dose-dependent effects of 3-iodothyronamine (T₁AM) on kidney and heart metabolism in mice.
- To quantitatively assess metabolic changes using cryofluorescence imaging of the NADH redox ratio (NADH RR).
- To determine if T₁AM exhibits tissue-specific metabolic effects at varying concentrations.
Main Methods:
- Mice were treated with low (10 mg/kg) and high (25 mg/kg) doses of 3-iodothyronamine (T₁AM).
- A cryofluorescence imaging instrument was employed to measure the NADH redox ratio (NADH RR) in kidney and heart tissues.
- NADH RR values from T₁AM-treated mice were compared to those from control mice.
Main Results:
- High-dose T₁AM significantly increased oxidative stress in mouse kidneys by 19% (P = 0.047), indicated by a higher NADH RR.
- Low-dose T₁AM showed no significant effect on kidney NADH RR compared to controls.
- In the heart, both low and high doses of T₁AM increased NADH RR, suggesting a protective effect against oxidative stress, with the high dose showing a 14% increase (P = 0.008).
Conclusions:
- 3-iodothyronamine (T₁AM) exhibits dose- and tissue-specific metabolic effects.
- High-dose T₁AM increases oxidative stress in kidneys but confers a protective effect on the heart.
- T₁AM may modulate metabolism through alternative pathways depending on the dose and target tissue.
