Anti-oxidant enzyme activities and expression and oxidative damage in patients with non-immediate reactions to drugs.
Adverse drug reactions with an immunological basis (ADRIB) may involve activation of other concomitant, non-specific mechanisms, amplifying the specific response and contributing to the severity and duration. One concomitant mechanism could be the generation of reactive oxygen species (ROS) and/or their detoxification by anti-oxidants, including anti-oxidant enzymes. We analysed the activity of the anti-oxidant enzymes Cu/Zn-superoxide dismutase (SOD), catalase (CAT) and cellular glutathione peroxidase (GPX), as well as certain markers of oxidative damage (thiobarbituric acid reactive substances (TBARS) and carbonyl content) in peripheral blood mononuclear cells from patients with non-immediate ADRIB using spectrophotometric methods and the anti-oxidant enzymes expression by quantitative real-time reverse transcription-polymerase chain reaction. SOD activity and expression were increased in all types of non-immediate reactions (urticaria, maculopapular exanthema and toxic epidermal necrolysis). Regarding oxidative damage, TBARS were increased in urticaria and maculopapular exanthema, and carbonyl groups in all types of reactions. Our observations indicate that oxidative damage occurs in non-immediate reactions. Carbonyl stress and the inadequacy of the anti-oxidant defences are probable causes.
Cornejo-Garcia
J A
JA
Research Laboratory for Allergic Diseases, Carlos Haya Hospital, Málaga, Spain.
Mayorga
C
C
Torres
M J
MJ
Fernandez
T D
TD
R-Pena
R
R
Bravo
I
I
Mates
J M
JM
Blanca
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000032:analysis / Q000235:genetics; D004342:Drug Hypersensitivity / Q000201:enzymology*; D004789:Enzyme Activation; D005260:Female; D005979:Glutathione Peroxidase / Q000032:analysis / Q000235:genetics; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000201:enzymology* / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013053:Spectrophotometry; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000032:analysis / Q000235:genetics; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014581:Urticaria / Q000201:enzymology
D000975:Antioxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase