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 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 F_1α (PGF_1α) 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 PGF_2α, 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-PGF_1α (P<0.05) in control and diabetic tissues, whereas PGF_2α, PGE₂ and TXB₂ levels, and PGF_2α 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^-1of α-tocopherol (vitamin E) have diminished placental PGF_2α and TXB₂ production and lipoperoxide levels. The results show a higher TXB₂ and a decreased 6-keto-PGF_1α 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 α-tocopherol in diabetic pregnancies.