title: Optical imaging of mitochondrial redox state in rodent models with 3-iodothyronamine.
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.
authors.affiliation: Biophotonics Laboratory, Department of Electrical Engineering and Computer Science, University of Wisconsin Milwaukee, Milwaukee, WI 53211-3029, USA.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Ghanian
authors.forename: Sepideh
authors.initials: S
authors.lastname: Maleki
authors.forename: Hannah
authors.initials: H
authors.lastname: Reiland
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Bütz
authors.forename: Grazia
authors.initials: G
authors.lastname: Chiellini
authors.forename: Fariba M
authors.initials: FM
authors.lastname: Assadi-Porter
authors.forename: Fariba-Assadi
authors.initials: FA
authors.lastname: Porter
authors.forename: Mahsa
authors.initials: M
authors.lastname: Ranji
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D005260:Female; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D061848:Optical Imaging; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress; D013970:Thyronines / Q000494:pharmacology*
chemical_list: C487948:3-iodothyronamine; D013970:Thyronines
keywords: 3-Iodothyronamine; FAD; NADH; mitochondrial redox ratio; optical imaging; oxidative stress