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2015 ; 20
(3
): 495-505
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Hyperbaric oxygen therapy (HBOT) suppresses biomarkers of cell stress and kidney
injury in diabetic mice
#MMPMID25648080
Verma R
; Chopra A
; Giardina C
; Sabbisetti V
; Smyth JA
; Hightower LE
; Perdrizet GA
Cell Stress Chaperones
2015[May]; 20
(3
): 495-505
PMID25648080
show ga
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.