title: 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.
authors: Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA, rysverma@gmail.com.
authors: Rajeev
authors: R
authors: Verma
authors: Avijeet
authors: A
authors: Chopra
authors: Charles
authors: C
authors: Giardina
authors: Venkata
authors: V
authors: Sabbisetti
authors: Joan A
authors: JA
authors: Smyth
authors: Lawrence E
authors: LE
authors: Hightower
authors: George A
authors: GA
authors: Perdrizet
mesh_terms: D000419:Albuminuria / Q000517:prevention & control / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000628:therapy / Q000652:urine*; D003928:Diabetic Nephropathies / Q000517:prevention & control / Q000652:urine*; D006931:Hyperbaric Oxygenation; D008297:Male; D008820:Mice, Obese; D018384:Oxidative Stress; D051437:Renal Insufficiency / Q000517:prevention & control / Q000652:urine*
chemical_list: D015415:Biomarkers; D003404:Creatinine
references: J Thorac Cardiovasc Surg. 2005 Dec;130(6):1623-30
references: 16308008
references: Endokrynol Pol. 2010 May-Jun;61(3):275-9
references: 20602302
references: Free Radic Res. 2007 Mar;41(3):274-81
references: 17364955
references: Carcinogenesis. 2001 Dec;22(12):1979-85
references: 11751428
references: Am J Physiol Renal Physiol. 2003 Jun;284(6):F1138-44
references: 12736165
references: Eur J Vasc Endovasc Surg. 2003 Jun;25(6):513-8
references: 12787692
references: Diabetes Care. 2003 Aug;26(8):2378-82
references: 12882865
references: QJM. 2004 Jul;97(7):385-95
references: 15208426
references: Science. 2004 Oct 15;306(5695):457-61
references: 15486293
references: Radiat Res. 1983 Aug;95(2):298-302
references: 6351157
references: Mol Med. 2008 Jul-Aug;14(7-8):485-92
references: 18431463
references: Kidney Int. 2008 Oct;74(8):1059-69
references: 18650797
references: Exp Biol Med (Maywood). 2008 Nov;233(11):1448-53
references: 18703748
references: Cell Stress Chaperones. 2009 Mar;14(2):113-5
references: 18720028
references: J Foot Ankle Surg. 2008 Nov-Dec;47(6):515-9
references: 19239860
references: Neuroscience. 2009 Apr 10;159(4):1309-15
references: 19185051
references: Adv Cancer Res. 2009;104:171-210
references: 19878777
references: Colloids Surf B Biointerfaces. 2011 Mar;83(1):128-32
references: 21131185
references: EMBO Mol Med. 2011 Jan;3(1):5-20
references: 21204265
references: Diabet Med. 2011 Feb;28(2):186-90
references: 21219427
references: Stroke. 2011 Feb;42(2):484-90
references: 21164135
references: Am J Physiol Renal Physiol. 2011 Feb;300(2):F301-10
references: 21147843
references: Inhal Toxicol. 2011 Feb;23(3):166-72
references: 21391785
references: Curr Opin Pediatr. 2011 Apr;23(2):194-200
references: 21252674
references: Int J Clin Exp Pathol. 2011 Mar;4(3):255-66
references: 21487521
references: Pediatr Nephrol. 2011 Jul;26(7):1031-7
references: 21193931
references: J Surg Res. 2011 Oct;170(2):e271-7
references: 21816440
references: Clin Toxicol (Phila). 2011 Oct;49(8):720-8
references: 21970770
references: J Surg Res. 2011 Nov;171(1):41-6
references: 20421116
references: Acta Cir Bras. 2011 Dec;26(6):463-9
references: 22042109
references: Diabetes Metab Res Rev. 2012 Feb;28 Suppl 1:78-84
references: 22271728
references: Biochim Biophys Acta. 2012 May;1822(5):753-83
references: 22108204
references: Biochim Biophys Acta. 2012 May;1822(5):729-36
references: 22186191
references: J Trauma Acute Care Surg. 2012 Mar;72(3):650-9
references: 22491549
references: Kidney Int. 2012 Jul;82(2):172-83
references: 22437410
references: Cell Metab. 2012 Aug 8;16(2):144-52
references: 22883229
references: Immunol Rev. 2012 Sep;249(1):116-34
references: 22889219
references: Semin Nephrol. 2012 Sep;32(5):445-51
references: 23062985
references: Cochrane Database Syst Rev. 2012;10:CD008176
references: 23076940
references: Int Wound J. 2012 Dec;9(6):665-76
references: 22372584
references: Cell Stress Chaperones. 2013 Jan;18(1):97-107
references: 22855227
references: Toxicol Sci. 2013 Jan;131(1):13-25
references: 23019274
references: Diabetes. 2013 Nov;62(11):3647-55
references: 24158990
references: Curr Biol. 2014 May 19;24(10):R453-62
references: 24845678
references: Cell Stress Chaperones. 2014 Jul;19(4):447-64
references: 24523032
references: Diabetes Care. 1996 Dec;19(12):1338-43
references: 8941460
references: Exp Eye Res. 1997 Sep;65(3):435-43
references: 9299180
references: J Biol Chem. 1999 Mar 12;274(11):6875-81
references: 10066740
references: Mutat Res. 1999 Jul 16;428(1-2):83-9
references: 10517981
references: J Am Soc Nephrol. 2005 Jan;16(1):27-45
references: 15563560
references: Science. 2005 Jan 21;307(5708):384-7
references: 15662004
references: J Clin Invest. 2005 May;115(5):1111-9
references: 15864338
references: J Am Soc Nephrol. 2009 Dec;20(12):2503-12
references: 19729434
references: Int J Clin Exp Pathol. 2009;3(2):177-88
references: 20126586
references: Nat Biotechnol. 2010 May;28(5):436-40
references: 20458311
references: Physiol Genomics. 2007 Apr 24;29(2):99-108
references: 17190852
references: Brain Res. 2008 May 19;1210:223-9
references: 18407255
references: Wound Repair Regen. 2008 May-Jun;16(3):321-30
references: 18471250
references: Diabetes. 2008 Jun;57(6):1446-54
references: 18511445
references: Cell Stress Chaperones. 2001 Apr;6(2):164-71
references: 11599578
references: Nat Biotechnol. 2010 May;28(5):463-9
references: 20458316
references: Ann N Y Acad Sci. 2010 Jun;1197:178-83
references: 20536847
references: Cell Stress Chaperones. 2010 Jul;15(4):431-42
references: 19949909
references: ScientificWorldJournal. 2006;6:425-41
references: 16604253