Exp Mol Med.  2010 Mar;42(3):223-232. 10.3858/emm.2010.42.3.024.

Suppression of ROS generation by 4,4'-diaminodiphenylsulfone in non-phagocytic human diploid fibroblasts

• Cho SC
• Rhim JH
• Son YH
• Lee SJ
• Park SC

• KMID: 946655
• DOI: http://doi.org/10.3858/emm.2010.42.3.024

Abstract

The action mode of 4,4'-diaminodiphenylsulfone (DDS) is still under debate, although it has long been used in treatment of several dermatologic diseases including Hansen's disease. In this study, we tested the effect of DDS as an antioxidant on paraquat-induced oxidative stress in non-phagocytic human diploid fibroblasts (HDFs). Overall, preincubation of HDFs with DDS prevented the oxidative stress and the resulting cytotoxic damages caused by paraquat in these cells. The specific effects of DDS in paraquat-treated HDFs are summarized as follows: a) reducing the expression of NADPH oxidase 4 (NOX4) by inhibiting paraquat-induced activation of PKC; b) inhibiting paraquat-induced decreases in mitochondrial complex protein levels as well as in membrane potentials; c) consequently, inhibiting the generation of cytosolic and mitochondrial superoxide anions. Taken together, these findings suggest that DDS would suppress the radical generation in non-phagocytic HDFs during oxidative stress, and that DDS might have the extended potential to be used further in prevention of other oxidative stress-related pathologies.

Keyword

antioxidants; leprosy; NADPH oxidase; oxidative stress; paraquat

MeSH Terms

Biphenyl Compounds/metabolism
Cell Death/drug effects
Cell Survival/drug effects
Dapsone/*pharmacology
*Diploidy
Enzyme Activation/drug effects
Fibroblasts/*cytology/drug effects/enzymology/*metabolism
Free Radical Scavengers/metabolism
Gene Expression Regulation, Enzymologic/drug effects
Humans
Male
Mitochondria/drug effects/pathology
NADPH Oxidase/genetics/metabolism
Paraquat/toxicity
Phagocytosis/drug effects
Picrates/metabolism
Protein Kinase C/metabolism
RNA, Messenger/genetics/metabolism
Reactive Oxygen Species/*metabolism
Superoxides/metabolism