title: Effects of SAC on oxidative stress and NO availability in placenta: potential benefits to preeclampsia.
abstract: Preeclampsia (PE) is a major cause of fetal growth restriction and perinatal mortality, which involves oxidative stress and vasodilator signaling disorder. S-allyl-L-cysteine (SAC) is one of the most abundant compounds in garlic extracts, and possesses several biological activities. This research was designed to investigate the protective effects of SAC against H(2)O(2)-induced oxidative insults, as well as the effects on NO/cGMP signaling pathway in placenta. We used TEV-1 cells and placental explants to detect the effects of SAC. TEV-1 cells and human placental explants were separately exposed to SAC, H(2)O(2), or a combination of H(2)O(2) and SAC. Intracellular ROS was detected by flow cytometry; the NO level was detected by an NO metabolites (NOx) assay; the cGMP level was simultaneously measured by the method of radioimmunoassay; the expression of eNOS in TEV-1 cells was measured by immunochemistry and Western blot. Our findings showed that H(2)O(2) treatment increased ROS productions in TEV-1 cells and significantly decreased cGMP and NO level either in TEV-1 cells or explants compared to the control groups (p < 0.05). The expression of eNOS in TEV-1 cells also significantly decreased in H(2)O(2) treated group compared to the control group (p < 0.05). Co-treatment of H(2)O(2) and SAC significantly decreased ROS productions, and increased NO, cGMP and eNOS level compared to the H(2)O(2) treated alone groups (p < 0.05), which were all reverted back to near control levels. Further more, SAC treatment increased NO and cGMP level of TEV-1 cells and explants in a dose-dependent manner even at non-oxidative stress status (p < 0.05). However, when the TEV-1 cells were cultured in the presence of NOS inhibitor (L-NAME) and NO donor (SNP), additional SAC treatment still significantly increased the NO level in comparison with SAC non-treated group (p < 0.05). In conclusion, these results demonstrate that ROS (H(2)O(2)-mediated) can induce insults to NO/cGMP pathway, while SAC could antagonize this insult. And SAC also possesses the ability to increase NO and cGMP level at non-oxidative stress status in TEV-1 cells and placenta explants. SAC is therefore hypothesized to be a potential drug for PE treatment.
authors.affiliation: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. yjtj2010@163.com
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: L
authors.initials: L
authors.lastname: Feng
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress / Q000187:drug effects*; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000517:prevention & control*; D011247:Pregnancy
chemical_list: D009569:Nitric Oxide; C065299:S-allylcysteine; D006861:Hydrogen Peroxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP; D003545:Cysteine