Evolution of oxidative stress parameters and response to oral vitamins E and C in streptozotocin-induced diabetic rats.
Type I diabetes in humans and streptozotocin (STZ)-induced diabetes in rats has been associated with oxidative stress, but antioxidant therapy has given contradictory results, in part related to the absence of common conditions used to evaluate in-vivo antioxidant properties. This prompted the study of an experimental model of antioxidant therapy in STZ-treated rats. Adult female rats received STZ (50 mgkg(-1)) and were studied 7 or 14 days later. Adipose tissue weight progressively decreased with the time of treatment, whereas plasma triglycerides increased at 7 days, before returning to control values at 14 days after STZ treatment. STZ diabetic rats had increased plasma thiobarbituric acid reacting substances and alpha-tocopherol levels, but the latter variable was decreased when corrected for total lipids. STZ diabetic rats showed a higher GSSG/GSH ratio at Day 14 and lower GSH + GSSG at Day 7 in liver. To evaluate the effect of short-term antioxidant therapy, rats received 5 doses of vitamins C and E over 3 days before being killed on Day 14. Treatment with antioxidants decreased plasma lactic acid and thiobarbituric acid reacting substances, as well as urine 8-isoprostane, and decreased plasma uric acid in controls. Vitamins increased the plasma alpha-tocopherol/lipids ratio only in control rats, although the plasma and liver alpha-tocopherol concentration increased in both groups. STZ diabetic rats showed moderate oxidative stress and treatment with antioxidant vitamins caused a significant change in a selected group of oxidative stress markers, which reflected an improvement in some of the complications associated with this disease. The present experimental conditions can be used as a sensitive experimental model to study the responsiveness of diabetes to other antioxidant interventions.
Facultad de Farmacia, Universidad San Pablo-CEU, Urbanización Montepríncipe, Boadilla del Monte, 28668 Madrid, Spain. ruperez@ceu.es
Francisco J
FJ
Rupérez
Diana
D
García-Martínez
Beatriz
B
Baena
Nuria
N
Maeso
Alejandro
A
Cifuentes
Coral
C
Barbas
Emilio
E
Herrera
D000284:Administration, Oral; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D013997:Time Factors; D014527:Uric Acid / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D014527:Uric Acid; D013311:Streptozocin; D005978:Glutathione; D001205:Ascorbic Acid