Hypoxic preconditioning attenuates lipopolysaccharide-induced oxidative stress in rat kidneys

Chih Ching Yang, Ming Chieh Ma, Chiang Ting Chien, Ming Shiou Wu, Wan Kuan Sun, Chau Fong Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


Chronic hypoxic (CH) preconditioning reduces superoxide-induced renal dysfunction via the upregulation of superoxide dismutase (SOD) activity and contents. Endotoxaemia reduces renal antioxidant status. We hypothesize that CH preconditioning might protect the kidney from subsequent endotoxaemia-induced oxidative injury. Endotoxaemia was induced by intraperitoneal injection of lipopolysaccharide (LPS; 4 mg kg-1) in rats kept at sea level (SL) and rats with CH in an altitude chamber (5500 m for 15 h day-1) for 4 weeks. LPS enhanced xanthine oxidase (XO) and gp91phox (catalytic subunit of NADPH oxidase) expression associated with burst amount of superoxide production from the SL kidney surface and renal venous blood detected by lucigenin-enhanced chemiluminescence. LPS induced a morphologic-independent renal dysfunction in baseline and acute saline loading stages and increased renal IL-1β protein and urinary protein concentration in the SL rats. After 4 weeks of induction, CH significantly increased Cu/ZnSOD, MnSOD and catalase expression (16 ± 17, 128 ± 35 and 48 ± 21, respectively) in renal cortex, and depressed renal cortex XO (44 ± 16%) and renal cortex (20 ± 9%) and medulla (28 ± 11%) gp91phox when compared with SL rats. The combined effect of enhanced antioxidant proteins and depressed oxidative proteins significantly reduced LPS-enhanced superoxide production, renal XO and gp91phox expression, renal IL-1β production, and urinary protein level. CH also ameliorated LPS-induced renal dysfunction in the baseline and acute saline loading periods. We conclude that CH treatment enhances the intrarenal antioxidant/oxidative protein ratio to overcome endotoxaemia-induced reactive oxygen species formation and inflammatory cytokine release.

Original languageEnglish
Pages (from-to)407-419
Number of pages13
JournalJournal of Physiology
Issue number1
Publication statusPublished - 2007 Jul 1
Externally publishedYes

ASJC Scopus subject areas

  • Physiology


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