Antioxidant effect of a novel synthetic hydrogen sulfide releasing Danshensu derivative and its clinical implications  

作　　者：Jin-song BIAN 

机构地区：[1]Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, PR Singapore

出　　处：《中国药理学与毒理学杂志》2018年第4期273-274,共2页Chinese Journal of Pharmacology and Toxicology

摘　　要：Oxidative stress induces apoptosis of many cells and arrest of their differentiation.Both Danshensu(DSS) and hydrogen sulfide(H_2S) produce significant antioxidant effect in various systems.In this study,we synthesized SDSS,a new H_2S-releasing compound derived from DSS,and studied its antioxidant effect in an H_2O_2-induced MC3T3-E1 osteoblastic cell injury model.We first characterized the H_2S releasing property of SDSS in both in vivo and in vitro models.HPLC chromatogram showed that intravenous injection of SDSS in adult rats released ADT-OH,a well proved H_2S sustained-release moiety,within several minutes in the rat plasma.Using an H_2S selective fluorescent probe,we further confirmed that SDSS released H_2S in MC3T3-E1 osteoblastic cells.Biological studies revealed that SDSS had no significant toxic effect but produced protective effects against H_2O_2-induced MC3T3-E1 cell apoptosis.SDSS also reversed the arrest of cell differentiation caused by H_2O_2 treatment.This was caused by the stimulatory effect of SDSS on bone sialo protein,runt-related transcription factor-2,collagen expression,alkaline phosphatase activity,and bone nodule formation.Further studies revealed that SDSS reversed the reduced superoxide dismutase activity and glutathione content,and the increased ROS production in H_2O_2 treated cells.In addition,SDSS significantly attenuated H_2O_2-induced activation of p38-,ERK1/2-,and JNK-MAPKs.SDSS also stimulated phosphatidylinositol 3-kinase/Akt signaling pathway.Blockade of this pathway attenuated the cytoprotective effect of SDSS.We also observed the effect of SDSS on aspirin-induced gastric injury and found that SDSS protected against aspirin-induced gastric damage.In conclusion,SDSS protects cells against H_2O_2-induced apoptosis by suppressing oxidative stress.Oxidative stress induces apoptosis of many cells and arrest of their differentiation.Both Danshensu（DSS） and hydrogen sulfide（H2S） produce significant antioxidant effect in various systems.In this study,we synthesized SDSS,a new H2S-releasing compound derived from DSS,and studied its antioxidant effect in an H2O2-induced MC3T3-E1 osteoblastic cell injury model.We first characterized the H2S releasing property of SDSS in both in vivo and in vitro models.HPLC chromatogram showed that intravenous injection of SDSS in adult rats released ADT-OH,a well proved H2S sustained-release moiety,within several minutes in the rat plasma.Using an H2S selective fluorescent probe,we further confirmed that SDSS released H2S in MC3T3-E1 osteoblastic cells.Biological studies revealed that SDSS had no significant toxic effect but produced protective effects against H2O2-induced MC3T3-E1 cell apoptosis.SDSS also reversed the arrest of cell differentiation caused by H2O2 treatment.This was caused by the stimulatory effect of SDSS on bone sialo protein,runt-related transcription factor-2,collagen expression,alkaline phosphatase activity,and bone nodule formation.Further studies revealed that SDSS reversed the reduced superoxide dismutase activity and glutathione content,and the increased ROS production in H2O2 treated cells.In addition,SDSS significantly attenuated H2O2-induced activation of p38-,ERK1/2-,and JNK-MAPKs.SDSS also stimulated phosphatidylinositol 3-kinase/Akt signaling pathway.Blockade of this pathway attenuated the cytoprotective effect of SDSS.We also observed the effect of SDSS on aspirin-induced gastric injury and found that SDSS protected against aspirin-induced gastric damage.In conclusion,SDSS protects cells against H2O2-induced apoptosis by suppressing oxidative stress.

关 键 词：细胞凋亡 丹神素 治疗方法 临床分析 

分 类 号：R735.7[医药卫生—肿瘤]