Hyperbaric oxygen therapy (HBOT) suppresses biomarkers of cell stress and kidney injury in diabetic mice

Abstract

The disease burden from diabetic kidney disease is large and growing. Effective therapies are lacking, despite an urgent need. Hyperbaric oxygen therapy (HBOT) activates Nrf2 and cellular antioxidant defenses; therefore, it may be generally useful for treating conditions that feature chronic oxidative tissue damage. Herein, we determined how periodic exposure to oxygen at elevated pressure affected type 2 diabetes mellitus-related changes in the kidneys of db/db mice. Two groups of db/db mice, designated 2.4 ATA and 1.5 ATA, were treated four times per week with 100 % oxygen at either 1.5 or 2.4 ATA (atmospheres absolute) followed by tests to assess kidney damage and function. The sham group of db/db mice and the Hets group of db/+ mice were handled but did not receive HBOT. Several markers of kidney damage were reduced significantly in the HBOT groups including urinary biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CyC) along with significantly lower levels of caspase-3 activity in kidney tissue extracts. Other stress biomarkers also showed trends to improvement in the HBOT groups, including urinary albumin levels. Expressions of the stress response genes NRF2, HMOX1, MT1, and HSPA1A were reduced in the HBOT groups at the end of the experiment, consistent with reduced kidney damage in treated mice. Urinary albumin/creatinine ratio (ACR), a measure of albuminuria, was significantly reduced in the db/db mice receiving HBOT. All of the db/db mouse groups had qualitatively similar changes in renal histopathology. Glycogenated nuclei, not previously reported in db/db mice, were observed in these three experimental groups but not in the control group of nondiabetic mice. Overall, our findings are consistent with therapeutic HBOT alleviating stress and damage in the diabetic kidney through cytoprotective responses. These findings support an emerging paradigm in which tissue oxygenation and cellular defenses effectively limit damage from chronic oxidative stress more effectively than chemical antioxidants.

Early hyperbaric oxygen therapy improves survival in a model of severe sepsis

“…HBOT preconditioning has also been shown to be protective in the case of ischemia-reperfusion injury (10,54), ameliorating skin damage from UV radiation (24) and improving the resolution of diabetic foot ulcers and chronic wounds (25). Moreover, HBOT was shown to induce protection and promote repair of the endothelium (26) and reduce the damage of diabetic kidney disease (51). Despite the positive effect of HBOT in various disease conditions, the underlying protective mechanism is still unclear.…”

Renal Effects of Hyperbaric Oxygen Therapy in Patients with Diabetes Mellitus: A Retrospective Study

“…Most data on the effect of HBOT on kidney function come from animal experimentation. Verma et al found a dose-dependent decrease in urinary albumin excretion and albumin/creatinine ratio in an HBOT-treated db/db diabetic mouse model [ 4 ]. Yilmaz et al found that HBOT has a synergistic effect with an angiotensin receptor blocker to reduce proteinuria in the adriamycin rodent model of focal segmental glomerulosclerosis (FSGS) [ 5 ].…”

“…ese same factors are implicated in the pathogenesis of microvascular complications of diabetes in the eye and in the kidney [3]. is suggests HBOT might be potentially harmful for patients with diabetes; however, animal studies show reduced proteinuria with HBOT treatments [4][5][6]. Virtually, no clinical data exist on the effect of HBOT on proteinuria and renal function in patients with diabetes mellitus, despite its widespread use in these patients.…”

Influence of hyperbaric oxygenation and its use in urinary tract diseases

“…The authors of this experiment demonstrate that multiple exposures of tissue to the oxidative stresses induced in hyperbaric conditions, activate the antioxidant mechanisms in these tissues. It makes them more resistant to the chronic effect of cell stress and thus limits the destruction caused by a chronic disease, in this case diabetes [8].…”