Oxidative stress and altered prostanoid production in the placenta of streptozotocin-induced diabetic rats

Abstract

The oxidative stress in placental tissues during late pregnancy, as well asthe relationship between reactive oxygen species (ROS) and the arachidonicacid (AA) pathway was evaluated in a neonatal streptozotocin (STZ)-induceddiabetic rat model. Lipoperoxide levels are increased in diabetic tissuescompared with control tissues (P&lt;0.001) and they seemto increase throughout the development of gestation both in control(P&lt;0.05) and STZ-induced diabetic(P&lt;0.001) rats. Superoxide dismutase (SOD) activityis not modified on different days of pregnancy, but enzymatic activity islower in diabetic tissues than in control tissues(P&lt;0.01). Labour is preceded by an increase inplacental 14C-prostaglandin conversion from14C-AA in control and diabetic animals(P&lt;0.05) and the thromboxane B<emph type="8">2(TXB<emph type="8">2)&sol;6-keto-prostaglandinF<emph type="8">1&alpha; (PGF<emph type="8">1&alpha;) ratio ishigher in diabetic placental tissues than in controls. The addition of SOD andglutathione to the incubation medium does not modify prostanoid levels incontrol rats, but does decrease the AA conversion toPGF<emph type="8">2&alpha;, PGE<emph type="8">2 andTXB<emph type="8">2 (P&lt;0.05) in diabeticplacenta. Superoxide radical generation (hypoxanthine&sol;xanthine oxidase orhydrogen peroxide added to the incubation medium) produces a decrease in6-keto-PGF<emph type="8">1&alpha; (P&lt;0.05) incontrol and diabetic tissues, whereas PGF<emph type="8">2&alpha;,PGE<emph type="8">2 and TXB<emph type="8">2 levels, andPGF<emph type="8">2&alpha; and TXB<emph type="8">2 productionare increased in control and diabetic animals respectively(P&lt;0.05). Diabetic pregnant rats supplemented with adiet containing 400 mg day-1of &alpha;-tocopherol(vitamin E) have diminished placental PGF<emph type="8">2&alpha; andTXB<emph type="8">2 production and lipoperoxide levels. The resultsshow a higher TXB<emph type="8">2 and a decreased6-keto-PGF<emph type="8">1&alpha; placental production that may belinked to increased oxidative stress and to a reduced antioxidant capacity inSTZ-induced diabetic rats. These imbalances, probably involved in abnormalplacental structure and function, may potentially be corrected with dietarysupplementation of &#945;-tocopherol in diabetic pregnancies.