Reactive oxygen species cause diabetes-induced decrease in renal oxygen tension.
OBJECTIVE
Augmented formation of reactive oxygen species (ROS) induced by hyperglycaemia has been suggested to contribute to the development of diabetic nephropathy. This study was designed to evaluate the influence of streptozotocin (STZ)-induced diabetes mellitus, as well as the effects of preventing excessive ROS formation by alpha-tocopherol treatment, on regional renal blood flow, oxygen tension and oxygen consumption in anaesthetized Wistar Furth rats.


METHODS
Non-diabetic and STZ-diabetic rats were investigated after 4 weeks with or without dietary treatment with the radical scavenger DL-alpha-tocopherol (vitamin E, 5%). A laser-Doppler technique was used to measure regional renal blood flow, whilst oxygen tension and consumption were measured using Clark-type microelectrodes.


RESULTS
Renal oxygen tension, but not renal blood flow, was lower throughout the renal parenchyma of diabetic rats when compared to non-diabetic control rats. The decrease in oxygen tension was most pronounced in the renal medulla. Renal cellular oxygen consumption was markedly increased in diabetic rats, predominantly in the medullary region. Diabetes increased lipid peroxidation and protein carbonylation in the renal medulla. Treatment with alpha-tocopherol throughout the course of diabetes prevented diabetes-induced disturbances in oxidative stress, oxygen tension and consumption. The diabetic animals had a renal hypertrophy and a glomerular hyperfiltration, which were unaffected by alpha-tocopherol treatment.


CONCLUSIONS
We conclude that oxidative stress occurs in kidneys of diabetic rats predominantly in the medullary region and relates to augmented oxygen consumption and impaired oxygen tension in the tissue.
Palm
F
F
Department of Medical Cell Biology, Biomedical Center, Box 571, 751 23 Uppsala, Sweden. Fredrik.Palm@medcellbiol.uu.se
Cederberg
J
J
Hansell
P
P
Liss
P
P
Carlsson
P-O
PO
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004032:Diet; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007672:Kidney Cortex / Q000187:drug effects / Q000503:physiopathology; D007677:Kidney Function Tests; D007679:Kidney Medulla / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011920:Rats, Inbred WF; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D024502:alpha-Tocopherol / Q000494:pharmacology
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D024502:alpha-Tocopherol