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

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Cell Stress and Chaperones Aims and scope

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.

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Acknowledgments

We thank OxyHeal Health Group, Inc., for funding and their CEO W. T. “Ted” Gurneè for his vision to extend the applications of HBOT to further improve human health care.

The Mouse Metabolic Phenotypic Center at Yale University is funded by a grant from the NIH/NIDDK # U24 DK-059635.

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Authors and Affiliations

  1. Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA

    Rajeev Verma, Avijeet Chopra, Charles Giardina & Lawrence E. Hightower

  2. Renal Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Venkata Sabbisetti

  3. Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, USA

    Joan A. Smyth

  4. Department of Emergency Medicine, University of California, San Diego, La Jolla, CA, USA

    George A. Perdrizet

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  1. Rajeev Verma
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  2. Avijeet Chopra
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  3. Charles Giardina
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  4. Venkata Sabbisetti
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Correspondence to Rajeev Verma.

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Verma, R., Chopra, A., Giardina, C. et al. Hyperbaric oxygen therapy (HBOT) suppresses biomarkers of cell stress and kidney injury in diabetic mice. Cell Stress and Chaperones 20, 495–505 (2015). https://doi.org/10.1007/s12192-015-0574-3

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