Owing to the increasing incidence and prevalence of inflammatory bowel disease(IBD)worldwide,effective and safe treatments for IBD are urgently needed.Hydrogen sulfide(H2S)is an endogenous gasotransmitter and plays an...Owing to the increasing incidence and prevalence of inflammatory bowel disease(IBD)worldwide,effective and safe treatments for IBD are urgently needed.Hydrogen sulfide(H2S)is an endogenous gasotransmitter and plays an important role in inflammation.To date,H2S-releasing agents are viewed as potential anti-inflammatory drugs.The slow-releasing H_(2)S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione(ADT-OH),known as a potent therapeutic with chemopreventive and cytoprotective properties,has received attention recently.Here,we reported its anti-inflammatory effects on dextran sodium sulfate(DSS)-induced acute(7 days)and chronic(30 days)colitis.We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length.Moreover,ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway.In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels.In addition,ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter,Mucispirillum,Parasutterella,and Desulfovibrio.Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines.Collectively,ADT-OH is safe without any short-term(5 days)or long-term(30 days)toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.展开更多
基金supported by grants from the National Natural Science Foundation of China (Nos.82130106 and 32250016)Nanjing Special Fund for Life and Health Science and Technology (No.202110016)Changzhou Municipal Department of Science and Technology (Nos.CZ20210010,CJ20210024,and CJ20220019).
文摘Owing to the increasing incidence and prevalence of inflammatory bowel disease(IBD)worldwide,effective and safe treatments for IBD are urgently needed.Hydrogen sulfide(H2S)is an endogenous gasotransmitter and plays an important role in inflammation.To date,H2S-releasing agents are viewed as potential anti-inflammatory drugs.The slow-releasing H_(2)S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione(ADT-OH),known as a potent therapeutic with chemopreventive and cytoprotective properties,has received attention recently.Here,we reported its anti-inflammatory effects on dextran sodium sulfate(DSS)-induced acute(7 days)and chronic(30 days)colitis.We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length.Moreover,ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway.In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels.In addition,ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter,Mucispirillum,Parasutterella,and Desulfovibrio.Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines.Collectively,ADT-OH is safe without any short-term(5 days)or long-term(30 days)toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.
