Protective Effects of Hydrogen Sulfide Against Cigarette Smoke Exposure-Induced Placental Oxidative Damage by Alleviating Redox Imbalance via Nrf2 Pathway in Rats

Background/Aims: Cigarette smoke exposure (CSE) during pregnancy is a well-recognized health hazard that causes placental damage. Hydrogen sulfide (H 2 S) has been reported to protect multiple organs from injury. However, the protective effects of H 2 S have not been tested in the placenta. This study aimed to explore the potential of H 2 S in protecting placenta against oxidative injury induced by CSE during pregnancy and the possible underlying mechanisms. Methods: Pregnant SD rats were randomly divided into 4 groups: NaCl, NaHS (a donor of H 2 S), CSE and CSE+NaHS. Placental oxidative damage was detected by 8-hydroxy-2-deoxyguanosine (8-OHdG) stain and malondialdehyde (MDA) assay. Placental redox status was assessed by measuring reactive oxygen species (ROS), total antioxidant capacity (T-AOC) and glutathione (GSH) levels, as well as copper/zinc SOD (SOD1), manganese SOD (SOD2), catalase (CAT) and glutathione peroxidase (GPx) activities and expressions. Meanwhile, nuclear factor erythroid 2-related factor 2 (Nrf2) was analyzed by immunohistochemistry, real-time PCR and Western blot. Results: We found that NaHS markedly reduced the elevated levels of 8-OHdG and MDA induced by CSE. Further, NaHS treatment effectively mitigated CSE-induced placental redox imbalance by inhibiting ROS production, restoring T-AOC level, increasing GSH/GSSG ratio, and augmenting SOD1 SOD2, CAT and GPx activities and expressions. More notably, NaHS administration also reversed the aberrant decrease of Nrf2 due to CSE in rat placentas. Conclusion: Our data demonstrate that H 2 S can protect against CSE-induced placental oxidative damage probably by alleviating redox imbalance via Nrf2 pathway.