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The early effects of uninephrectomy on rat kidney metabolic state using optical imaging
Author(s) -
Mehrvar Shima,
Foomani Farnaz H.,
Shimada Satoshi,
Yang Chun,
Zheleznova Nadezhda N.,
Mostaghimi Soudeh,
Cowley Allen W.,
Ranji Mahsa
Publication year - 2020
Publication title -
journal of biophotonics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.877
H-Index - 66
eISSN - 1864-0648
pISSN - 1864-063X
DOI - 10.1002/jbio.202000089
Subject(s) - nox4 , flavin adenine dinucleotide , kidney , nicotinamide adenine dinucleotide , nadph oxidase , chemistry , reactive oxygen species , endocrinology , medicine , nicotinamide adenine dinucleotide phosphate , oxidase test , nad+ kinase , biology , biochemistry , cofactor , enzyme
Abstract Uninephrectomy (UNX) is known to result in structural and metabolic changes to the remaining kidney, although it is uncertain if this alters the mitochondrial redox state and how soon such changes may occur. A custom‐designed fluorescence cryo‐imaging technique was used to quantitatively assess the effect of UNX by measuring the levels of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) in the remaining kidney. Kidneys were snap‐frozen 3 days following UNX, and the intrinsic fluorescence of NADH and FAD were optically acquired. The 3D images were created to characterize the NADH/FAD redox ratios (RR) of the right kidneys, which underwent UNX and the remaining kidneys 3 days following UNX. Both the NADPH‐oxidases (Nox2 and Nox4) and the mitochondria are the main sources of reactive oxygen species (ROS) production in tubular epithelial cells. Responses to the UNX were obtained in kidneys of normal Sprague Dawley (SD) rats, Dahl salt‐sensitive (SS) rats and SS rats in which NADPH‐oxidase isoform 4 (Nox4) was knocked out (SS Nox4−/− ). The results found that each of the strains exhibited similar increase in kidney weights averaging 17% after 3 days of UNX. SD and SS Nox4−/− rats both exhibited global reductions of the RR ( P < .05) with a similar tendency observed in SS rats ( P < .08), indicating increased ROS production. The unexpected reduction of the RR in the remnant kidneys of SS Nox4−/− rats indicates that mechanisms independent of H 2 O 2 produced from Nox4 may be responsible for this global increase of ROS. We propose that the reduced RR was largely a consequence of enhanced mitochondrial bioenergetics due to increased tubular workload of the remaining kidney. The data indicate that mitochondria become the dominant source of increased ROS following UNX and could represent an important hypertrophic signaling mechanism.