C.-C. Yang and M.-C. Ma contributed equally to this work.
Hypoxic preconditioning attenuates lipopolysaccharide-induced oxidative stress in rat kidneys
Article first published online: 25 JUN 2007
The Journal of Physiology
Volume 582, Issue 1, pages 407–419, July 2007
How to Cite
Yang, C.-C., Ma, M.-C., Chien, C.-T., Wu, M.-S., Sun, W.-K. and Chen, C.-F. (2007), Hypoxic preconditioning attenuates lipopolysaccharide-induced oxidative stress in rat kidneys. The Journal of Physiology, 582: 407–419. doi: 10.1113/jphysiol.2006.122747
- Issue published online: 25 JUN 2007
- Article first published online: 25 JUN 2007
- (Received 16 October 2006; accepted after revision 16 February 2007; first published online 22 February 2007)
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.