title: Intermittent hypoxia-induced renal antioxidants and oxidative damage in male mice: hormetic dose response.
abstract: Obstructive sleep apnea causes cardiovascular disease via chronic intermittent hypoxia (IH), which may be related to oxidative stress. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important cellular defense mechanism against oxidative stress by regulating its down-stream multiple antioxidants. The present study was to define whether IH can induce renal pathogenic damage and if so, whether Nrf2 and its down-stream antioxidants are involved in IH-induced pathogenic changes. Mice were culled for exposure to intermittent air as control or IH that consisted of 20.9% O2/ 8% O2 FIO2 alternation cycles (30 episodes per h) with 20 seconds at the nadir FIO2 for 12 h a day during daylight. Short-term IH exposure (3 - 7 days) induced significant increases in renal inflammatory response and antioxidant levels along with a reduction of the spontaneous content of malondialdehyde while long-term IH exposure (8 weeks) induced a significant decrease of antioxidant levels and significant increases of renal inflammation, oxidative damage, cell death, and fibrosis. This study suggests that IH induces a hormetic response, i.e.: short-term IH exposure is able to induce a protective response to protect the kidney from oxidative damage while long-term IH exposure is able to induce a damage effect on the kidney.
authors: The First Hospital of Jilin University, China and KCHRI at the Department of Pediatrics, University of Louisville, USA.
authors: Weixia
authors: W
authors: Sun
authors: Xia
authors: X
authors: Yin
authors: Yuehui
authors: Y
authors: Wang
authors: Yi
authors: Y
authors: Tan
authors: Lu
authors: L
authors: Cai
authors: Bo
authors: B
authors: Wang
authors: Jun
authors: J
authors: Cai
authors: Yaowen
authors: Y
authors: Fu
keywords: Intermittent hypoxia; Nrf2; kidney hypoxic damage; metallothionein
references: J Clin Invest. 2007 Dec;117(12):3810-20
references: 18037992
references: Chest. 2012 Jun;141(6):1422-1430
references: 22222188
references: J Cereb Blood Flow Metab. 2008 Aug;28(8):1469-77
references: 18506199
references: J Cell Physiol. 2011 Nov;226(11):2925-33
references: 21302291
references: Physiol Genomics. 2010 May;41(3):306-14
references: 20197421
references: FEBS Lett. 2000 Feb 18;468(1):53-8
references: 10683440
references: J Mol Cell Cardiol. 2007 Feb;42(2):343-51
references: 17188294
references: Heart Fail Rev. 2009 Sep;14(3):143-53
references: 18807180
references: PLoS One. 2011 Apr 29;6(4):e19029
references: 21559506
references: J Cell Physiol. 1994 Jul;160(1):61-8
references: 7517407
references: N Engl J Med. 2011 Feb 17;364(7):656-65
references: 21323543
references: Toxicol Lett. 2011 Jul 4;204(1):71-80
references: 21549813
references: FASEB J. 2006 Dec;20(14):2624-6
references: 17142801
references: Cytokine. 2000 Mar;12(3):246-52
references: 10704252
references: J Pathol. 2012 Feb;226(3):495-508
references: 21953180
references: Lung. 2006 Jan-Feb;184(1):43-9
references: 16598651
references: Circulation. 2006 Jan 31;113(4):544-54
references: 16432057
references: Antioxid Redox Signal. 2006 Jan-Feb;8(1-2):43-52
references: 16487036
references: Antioxid Redox Signal. 2007 Sep;9(9):1391-6
references: 17627473
references: Eur J Pharmacol. 2007 Dec 22;577(1-3):17-27
references: 17854798
references: Free Radic Biol Med. 2011 Dec 1;51(11):2073-81
references: 21964506
references: Diabetes. 2005 Jun;54(6):1829-37
references: 15919806
references: Fundam Appl Toxicol. 1995 Jun;26(1):99-106
references: 7657068
references: N Engl J Med. 1993 Apr 29;328(17):1230-5
references: 8464434
references: ILAR J. 2009;50(3):262-81
references: 19506313
references: Cardiovasc Ther. 2010 Oct;28(5):e72-91
references: 20626406
references: Am J Med Sci. 2012 Jun;343(6):458-61
references: 22112787
references: Blood Purif. 2003;21(3):253-7
references: 12784052
references: Glia. 2006 Nov 1;54(6):606-18
references: 16944453
references: Am J Physiol Renal Physiol. 2008 Oct;295(4):F1023-9
references: 18667485
references: Cell Signal. 2010 Oct;22(10):1413-9
references: 20363319
references: Biochemistry (Mosc). 2011 Apr;76(4):407-22
references: 21585316
references: Am J Respir Cell Mol Biol. 2005 May;32(5):395-403
references: 15695738
references: Exp Biol Med (Maywood). 2002 Jan;227(1):26-31
references: 11788780
references: Exp Gerontol. 2002 Dec;37(12):1481-7
references: 12559417