N-acetylcysteine and clotrimazole inhibit sickle erythrocyte dehydration induced by 1-chloro-2,4-dinitrobenzene.
Clotrimazole, a specific inhibitor of the Ca(2+) activated potassium (Gardos) channel, and the antioxidant N-acetylcysteine were found to inhibit the in vitro formation of high-density sickle cells induced by treatment with 1-chloro-2,4-dinitrobenzene (CDNB). The CDNB induced leakage of K(+) can be inhibited by treatment of SS erythrocytes with 20 mM N-acetylcysteine. We conclude that the effect of N-acetylcysteine in preventing K(+) efflux and formation of high-density sickle cells is related to its ability to protect the Gardos channel from oxidative damage caused by diminished levels of reduced glutathione. This effect is due to the ability of N-acetylcysteine to maintain an appropriate level of reduced glutathione and its direct antioxidant activity.
Shartava
A
A
Department of Structural and Cellular Biology, University of South Alabama, College of Medicine, Mobile, Alabama 36688, USA.
Shah
A K
AK
Goodman
S R
SR
D000111:Acetylcysteine / Q000494:pharmacology*; D000755:Anemia, Sickle Cell / Q000097:blood*; D002264:Carboxylic Acids / Q000494:pharmacology; D002352:Carrier Proteins / Q000097:blood / Q000187:drug effects; D003022:Clotrimazole / Q000494:pharmacology*; D003890:Desiccation; D004137:Dinitrochlorobenzene / Q000633:toxicity*; D004913:Erythrocytes, Abnormal / Q000187:drug effects*; D005978:Glutathione / Q000097:blood; D006801:Humans; D007192:Indenes / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011188:Potassium / Q000097:blood; D015221:Potassium Channels / Q000097:blood / Q000187:drug effects; D027981:Symporters; D000096922:K Cl- Cotransporters
D000111:Acetylcysteine; D002264:Carboxylic Acids; D002352:Carrier Proteins; D003022:Clotrimazole; D004137:Dinitrochlorobenzene; D005978:Glutathione; D007192:Indenes; D011188:Potassium; D015221:Potassium Channels; D027981:Symporters; D000096922:K Cl- Cotransporters; C059990:((dihydroindenyl)oxy)alkanoic acid