Pregnancy is a physiological state accompanied by a high energy demand and an increased oxygen requirement. Various compensatory adaptive changes, including increased ventilation for enhanced oxygen demand, occur with advancing pregnancy to meet the increasing requirements for proper bodily functions of the mother to fulfill the needs of the fetus [16
]. Such a condition may be responsible for raised oxidative stress in pregnancy. The hypothesis underpinning this study was that impaired antioxidant status in diabetic and hypertensive women during labor might contribute to an increased risk of fetal abnormality. As outlined earlier, substantial evidence from animal models suggested that increased oxidative stress in the developing embryo is an important cause of abnormality, and that this can be prevented by antioxidants [17
Our aim in the present study was to show the possibility of using the measured parameters as indicators of oxidative stress and antioxidant status during labor in diabetic, hypertensive, and healthy control women. In previous studies of antioxidant status in diabetics, abnormalities have usually been reported in the presence of diabetic complications or poor metabolic control. Indeed, in several studies antioxidant status and markers of lipid peroxidation have been normal in well-controlled diabetic subjects with no evidence of micro- or macroangiopathic complications [18
In the present study, we observed an increased level of plasma lipid peroxidation products (LPO) during labor in diabetic and hypertensive women. This may be attributed to over production of reactive oxygen species (ROS) or a deficiency of antioxidant defense. The results of the present study are in harmony with previous studies by Orhan et al. [20
] and Tiwari et al. [21
] who reported that the significant increase in plasma LPO in diabetic and anemic pregnant women, respectively, were parallel with a depletion of antioxidant enzymes as these enzymes are the major defense system of cells in normal aerobic reactions [22
Similarly, during labor, plasma GSH-Px activity in diabetic and hypertensive women was increased significantly when compared to control women. This finding was in accordance with previous reports [23
] and the finding of Orhan et al. [20
] who reported that erythrocyte GSH-Px activity was found to be significantly increased in hypertensive preeclamptic pregnancy and in insulin-dependent diabetic pregnancy. However, there are a number of conflicting reports as well [25
]. It can be assumed that at low levels of oxidants the enzyme is deactivated, but after a certain higher level it gets activated by same oxidant(s). Therefore, an increase in GSH-Px activity coupled with an increase in plasma lipid peroxides in the same groups can be interpreted as a compensatory mechanism of the enzyme in order to quench the increased levels of hydrogen peroxide. Therefore, elevated levels of GSH-Px activity in hypertensive and diabetic women during labor may be linked to increased oxidative stress, because it is well known that ROS, especially hydrogen peroxide stimulate GSH-Px activity. This is an expected outcome during the delivery of a fetus, since the high oxygen challenge occurring at birth might lead to increased formation of reactive oxygen species and subsequently hydrogen peroxide.
Our present data show that there was no statistically significant difference in plasma GSH-Red activity during labor in diabetic, hypertensive, and control women. However, Miranda Guisado et al. [27
] recently clarified glutathione redox cycle in hypertensive disorders of pregnancy and found a significant decrease in its reduced form GSH with a parallel increase in the oxidized form GSSG and an increment in both GSH-Px and GSH-Red activities. In our study, we observed that the plasma level of GSH-red activity in hypertensive group is higher than control group but the difference did not reach significant level. The reason for the discrepancy may be due to difference between activity level of GSH-Red in RBCs and plasma or may be explained by the physiological properties of the enzyme GSH-red. Moreover the pentose phosphate pathway may not be perturbed, as the availability of NADPH, a cofactor for GSH-red functioning be may still sufficient.
Glutathione is a major intracellular antioxidant. Glutathione and other thiols maintain the redox balance of cells, thereby preventing oxidative damage. GSH-Px catalyzes the oxidation of GSH to GSSG and reduces hydrogen peroxides (H2O2) to water. To maintain the balance between GSH and GSSG, the oxidized form of glutathione (GSSG) is reduced to GSH by GSH-red. For our future research, further assessment of GSH/GSSG ratio and hydrogen peroxides (H2O2) could give us more information about oxidant and antioxidant status in diabetic and hypertensive women during labor. Therefore, we will take that in our consideration and it will be verified in the erythrocytes and plasma of diabetic and hypertensive women during labor.
Plasma SOD activity of diabetic and hypertensive women during labor was significantly lower than its corresponding level in control women although erythrocytes possess highly efficient antioxidant enzymes, such as SOD and GSH-Px compared to other cell types [28
]. In the present study there were no differences in RBCs, WBCs, and platelet counts, and HB concentrations in different groups during labor. However, our results showed that diabetic and hypertensive women have lower SOD and higher GSH-Px activities than healthy control. Our results are in accordance with an earlier report [29
]. The observed reduction in SOD activity in hypertensive and diabetic women to that of normal control women could be associated with deleterious effect of hypertension and diabetes, as the superoxide anion that is being generated continuously by numerous sources throughout the body would not be inactivated effectively and lead to an increase in its concentration. Enhanced generation of superoxide anion would result in greater oxidative stress and lipid peroxidation. Decreased SOD activity during labor in diabetic, and hypertensive groups may be linked to increased hydrogen peroxide since it is well known that ROS, especially superoxide anion and hydrogen peroxide (H2
), inhibit SOD activity [30
]. SOD is a metalloprotein and accomplishes its antioxidant function by enzymatically detoxifying the peroxides (–OOH) and O2−
Plasma total antioxidants were significantly higher only in diabetic women as compared with the control group. Clinical biochemical parameters, such as urea and creatinine, were higher only in the hypertensive group when compared to the control. The significantly high level of urea and creatinine of these patients seem to be a result of a renal damage due to hypertension. On the other hand, plasma levels of fasting blood sugar were higher in diabetic women as compared with normal controls.
The present study shows elevated oxidative stress/lipid peroxidation in diabetic and hypertensive women during labor. Besides, SOD, GSH-Px, and total antioxidants seem to be appropriate biomarkers reflecting the status of antioxidant capacity in these diseases. The validation of these biomarkers for monitoring the efficiency of antioxidant supplementation during pregnancy should be further investigated. This supplementation may provide the prevention and/or attenuation of oxidative stress and enhancement of antioxidant status.