Research Paper Volume 13, Issue 8 pp 10955—10972
Hyperbaric oxygen therapy effectively alleviates D-galactose-induced-age-related cardiac dysfunction via attenuating mitochondrial dysfunction in pre-diabetic rats
- 1 Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- 2 Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- 3 Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand
- 4 Hyperbaric Oxygen Therapy Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
Received: December 14, 2020 Accepted: March 27, 2021 Published: April 16, 2021
https://doi.org/10.18632/aging.202970How to Cite
Copyright: © 2021 Bo-Htay et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Currently, the prevalence of obesity in aging populations is fast growing worldwide. Aging induced by D-galactose (D-gal) is proven to cause the worsening of cardiac dysfunction in pre-diabetic rats via deteriorating cardiac mitochondrial function. Hyperbaric oxygen therapy (HBOT) has been shown to attenuate D-gal-induced cognitive deterioration through decreased inflammation and apoptosis. We tested the hypothesis that HBOT alleviates D-gal induced cardiac dysfunction via improving mitochondrial function in pre-diabetic rats. Wistar rats (n=56) were fed normal diet or high-fat diet for 12 weeks. For subsequent 8 weeks, they were subcutaneously injected either vehicle (0.9% normal saline) or D-gal (150mg/kg/day). Rats were randomly subdivided into 7 groups at week 21: sham-treated (normal diet fed rats with vehicle (NDV), high-fat diet fed rats with vehicle (HFV), normal diet fed rats with D-gal (NDDg), high-fat diet fed rats with D-gal (HFDg)) and HBOT-treated (HFV, NDDg, HFDg). Sham rats received ambient pressure of oxygen while HBOT-treated ones received 100% oxygen given once daily for 60 minutes at 2 atmosphere absolute. HBOT reduced metabolic impairments, mitochondrial dysfunction and increased autophagy, resulting in an improvement of cardiac function in aged pre-diabetic rats.
Abbreviations
ATA: atmospheres absolute; Bax: B-cell lymphoma 2 associated X protein; Bcl-2: B-cell lymphoma 2; CGRP: calcitonin gene-related peptide; DAPI: 4',6-diamidino-2-phenylindole dihydrochloride; DBP: diastolic blood pressure; DCF: dichlorofluorescein; DCFH-DA: dichloro-dihydro-fluorescein diacetate dye; D-gal: D-galactose; dp/dt: rate of rise of left ventricular pressure; Drp1: dynamin-related protein 1; ECG: electrocardiogram; ECL: enhanced chemiluminescence detection reagents; EDP: end diastolic pressure; ESP: end systolic pressure; GAPDH: Glyceraldehyde 3-phosphate dehydrogenase; HBOT: hyperbaric oxygen therapy; HDL: high-density lipoprotein; HF: high-frequency band; HFD: high-fat diet; HFDg: high-fat diet fed rats with D-gal; HFV: high-fat diet fed rats with vehicle; HOMA: homeostatic model assessment; HPLC: high performance liquid chromatography; HR: heart rate; HRV: heart rat variability; JC-1: 5,5′,6,6′-tetrachloro-1,1′,3,3′tetraethylbenzimidazolcarbocyanine iodide dye; LC3II: microtubule associated light chain 3II; LDL: low-density lipoprotein; LF: low-frequency band; LVEDP: left ventricular end diastolic pressure; LVEF: left ventricular ejection fraction; LVESP: left ventricular end systolic pressure; MDA: malondialdehyde; Mfn1: mitofusin 1; Mfn2: mitofusin 2; ND: normal diet; NDDg: normal diet fed rats with D-gal; NDV: normal diet fed rats with vehicle; NSS: normal saline solution; P-V loop: pressure volume loop; p62: Sequestosome-1 (ubiquitin-binding protein); ROS: reactive oxygen species; SBP: systolic blood pressure; SC: subcutaneous injection; SEM: standard error of the mean; SV: stroke volume; TC: cholesterol; TEM: transmission electron microscope; TG: triglyceride; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling; VDAC: voltage-dependent anion channel.