Oxidative stress and altered prostanoid production in the placenta of streptozotocin-induced diabetic rats.
The oxidative stress in placental tissues during late pregnancy, as well as the relationship between reactive oxygen species (ROS) and the arachidonic acid (AA) pathway was evaluated in a neonatal streptozotocin (STZ)-induced diabetic rat model. Lipoperoxide levels are increased in diabetic tissues compared with control tissues (P<0.001) and they seem to increase throughout the development of gestation both in control (P<0.05) and STZ-induced diabetic (P<0.001) rats. Superoxide dismutase (SOD) activity is not modified on different days of pregnancy, but enzymatic activity is lower in diabetic tissues than in control tissues (P<0.01). Labour is preceded by an increase in placental 14C-prostaglandin conversion from 14C-AA in control and diabetic animals (P<0.05) and the thromboxane B2 (TXB2)/6-keto-prostaglandin F1alpha (PGF1alpha) ratio is higher in diabetic placental tissues than in controls. The addition of SOD and glutathione to the incubation medium does not modify prostanoid levels in control rats, but does decrease the AA conversion to PGF2alpha, PGE2 and TXB2 (P<0.05) in diabetic placenta. Superoxide radical generation (hypoxanthine/xanthine oxidase or hydrogen peroxide added to the incubation medium) produces a decrease in 6-keto-PGF1alpha (P<0.05) in control and diabetic tissues, whereas PGF2alpha, PGE2 and TXB2 levels, and PGF2alpha and TXB2 production are increased in control and diabetic animals respectively (P<0.05). Diabetic pregnant rats supplemented with a diet containing 400 mg day(-1) of alpha-tocopherol (vitamin E) have diminished placental PGF2alpha and TXB2 production and lipoperoxide levels. The results show a higher TXB2 and a decreased 6-keto-PGF1alpha placental production that may be linked to increased oxidative stress and to a reduced antioxidant capacity in STZ-induced diabetic rats. These imbalances, probably involved in abnormal placental structure and function, may potentially be corrected with dietary supplementation of alpha-tocopherol in diabetic pregnancies.
White
Veronica
V
Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Jawerbaum
Alicia
A
Sinner
Debora
D
Pustovrh
Carolina
C
Capobianco
Evangelina
E
González
Elida
E
D000818:Animals; D000831:Animals, Newborn; D016718:Arachidonic Acid / Q000378:metabolism; D016022:Case-Control Studies; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D008297:Male; D018384:Oxidative Stress; D036801:Parturition; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology
D011453:Prostaglandins; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D016718:Arachidonic Acid; D013311:Streptozocin; D013482:Superoxide Dismutase; D024502:alpha-Tocopherol