Hyperbaric oxygen therapy effectively alleviates D-galactose-induced-age-related cardiac dysfunction via attenuating mitochondrial dysfunction in pre-diabetic rats

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.

Hyperbaric oxygen therapy for healthy aging: From mechanisms to therapeutics

“…The myocardium of elderly diabetic patients is particularly vulnerable to the adverse effects of local and systemic factors caused by diabetes. In pre-diabetic rats after D-gal-induced aging, HBOT ameliorated the aggravation of cardiac dysfunctions [ 98 ], consistent with a previous clinical trial involving elderly diabetic patients, in which HBOT resulted in improved myocardial diastolic function [ 191 ]. Researchers also examined the effects of HBOT on myocardial function during normal aging.…”

“…Intriguingly, in two independent reports, HBOT respectively showed its ability to attenuate aging markers in the hippocampus of d -galactose (D-gal)-induced aging mice, as demonstrated by decreased number of SA-β-gal positive cells [ 66 ] and reduced expression of key components of the senescence program, such as p16, p21 and p53 [ 71 ]. It has also been shown that HBOT can reduce the number of SA-β-gal positive cells in cardiomyocytes in aging pre-diabetic rats [ 98 ]. In another study, researchers evaluated cellular senescence by lipofuscin, another established biomarker, and found senescent cells cleared from skin after HBOT [ 27 ].…”

“…Glucose homeostasis depends on appropriate insulin secretion and the sensitivity of receptors to insulin, both of which are impaired with advancing age [ 160 ] In two studies involving animal models of D-gal-induced aging and combined model of D-gal-induced aging and obesity, HBOT attenuated disturbances of glucose metabolism, mediated by restored insulin sensitivity instead of enhanced insulin secretion [ 66 , 98 ]. In another study, following a reduction in AGEs, the levels of TNF-α and IL-6, independent biomarkers predicting the development of insulin resistance and type 2 diabetes mellitus [ 161 ], were decreased significantly after HBOT in D-gal-induced aging mice [ 71 ].…”

“…Interestingly, HBOT also ameliorated obesity by reducing adipocyte hypertrophy in rats with metabolic syndrome [ 175 ] and diabetic rats with obesity [ 178 ], and in the former even significantly decreased body weight together with abdominal and epididymal fat [ 175 ]. However, no effect on lipid profile or body weight was observed in reports of aging or aging-obese rats [ 66 , 98 ]. It is unclear whether this contradiction is due to the assumption that diabetic rats are more sensitive to the effects of HBOT on lipid metabolism and obesity, or simply due to the differences in experimental methods.…”

“…Researchers also examined the effects of HBOT on myocardial function during normal aging. It was found that HBOT restored cardiac senescence marker expression and cardiac function parameters in D-gal-induced aging rats, even to the same level of the vehicle group [ 98 ]. HBOT used under different protocols yields inconsistent results in elderly subjects.…”