N-acetylcysteine (NAC) reverses the alterations in antioxidant enzymes seen in the reduced uterine perfusion pressure model (RUPP) of preeclampsia

We have previously shown that NAC reduced blood pressure without adverse fetal effects in the RUPP model. The objective of this study was to evaluate the intracellular antioxidant enzymes and to elucidate the protective mechanisms of NAC in the RUPP model. Timed pregnant Sprague-Dawley rats underwent sham surgery or the RUPP procedure on day 15/22 of pregnancy. In the RUPP animals, a laparotomy was performed and the infra-renal aorta and ovarian vessels were partially occluded using calibrated clips. The RUPP animals were assigned to treatment with NAC (100 mg/kg BID) or saline with the first dose given prior to the RUPP procedure. On day 21/22, a carotid catheter was placed and mean arterial pressures were measured. The pups were delivered and the placentas were collected and snap frozen. Placental expression of the antioxidant enzymes MnSOD and Cu/ZnSOD were determined by immunoblot analysis. Placental glutathione peroxidase and glutathione reductase enzyme activities were also assayed. Nonparametric statistical analysis was performed. There was a significant decrease in glutathione, glutathione peroxidase and glutathione reductase activity with the RUPP model. These changes were reversed by use of NAC. Cu/ZnSOD expression decreased while MnSOD activity increased with the RUPP model and these changes were also reversed with the use of NAC. We observed alterations in intracellular antioxidant enzymes associated with the RUPP model of preeclampsia. These changes were reversed by the use of NAC and may help to explain the improvement in maternal blood pressure and pup weight seen with treatment in the RUPP model.