title: Protective effect of 4,4'-diaminodiphenylsulfone against paraquat-induced mouse lung injury.
abstract: Although 4,4'-diaminodiphenylsulfone (DDS, dapsone) has been used to treat several dermatologic conditions, including Hansen disease, for the past several decades, its mode of action has remained a topic of debate. We recently reported that DDS treatment significantly extends the lifespan of the nematode C. elegans by decreasing the generation of reactive oxygen species. Additionally, in in vitro experiments using non-phagocytic human fibroblasts, we found that DDS effectively counteracted the toxicity of paraquat (PQ). In the present study, we extended our work to test the protective effect of DDS against PQ in vivo using a mouse lung injury model. Oral administration of DDS to mice significantly attenuated the lung tissue damage caused by subsequent administration of PQ. Moreover, DDS reduced the local expression of mRNA transcripts encoding inflammation-related molecules, including endothelin-1 (ET-1), macrophage inflammatory protein-1α (MIP-1α), and transforming growth factor-β (TGF-β). In addition, DDS decreased the PQ-induced expression of NADPH oxidase mRNA and activation of protein kinase Cμ (PKCμ). DDS treatment also decreased the PQ-induced generation of superoxide anions in mouse lung fibroblasts. Taken together, these data suggest the novel efficacy of DDS as an effective protective agent against oxidative stress-induced tissue damages.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute on Aging, Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Sung Chun
authors.initials: SC
authors.lastname: Cho
authors.forename: Ji Heon
authors.initials: JH
authors.lastname: Rhim
authors.forename: Hae Ri
authors.initials: HR
authors.lastname: Choi
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Son
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Kye Yong
authors.initials: KY
authors.lastname: Song
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Park
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000187:drug effects / Q000378:metabolism; D003622:Dapsone / Q000008:administration & dosage*; D019332:Endothelin-1 / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D006540:Herbicides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D055370:Lung Injury / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress; D010269:Paraquat / Q000037:antagonists & inhibitors* / Q000633:toxicity; D020011:Protective Agents / Q000008:administration & dosage*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism
chemical_list: D054405:Chemokine CCL3; D019332:Endothelin-1; D006540:Herbicides; D020011:Protective Agents; D016212:Transforming Growth Factor beta; D013481:Superoxides; D003622:Dapsone; C089212:protein kinase D; D011493:Protein Kinase C; D010269:Paraquat