Imbalance in superoxide dismutase/thioredoxin reductase activities in hypercholesterolemic subjects: relationship with low density lipoprotein oxidation.
BACKGROUND
There is a relationship among hypercholesterolemia, oxidative stress and inflammation in the atherogenesis. Thus, the objective of the present study was to assess paraoxonase (PON1), superoxide dismutase (SOD) and thioredoxin reductase (TrxR-1) activities and their relationship with lipids, oxidative stress and inflammation in subjects with different low density lipoprotein-cholesterol (LDL) levels.


METHODS
Serum lipids, highly sensitive C-reactive protein (hs-CRP), lipid and protein oxidation, oxidized LDL (LDLox) and LDLox autoantibodies (LDLoxAB) levels and enzymes activities were measured in a total of 116 subjects that were divided into the following groups according to their LDL levels: low-LDL group (LDL < 100 mg/dL, n = 23), intermediate-LDL group (LDL 100-160 mg/dL, n = 50) and high-LDL group (LDL > 160 mg/dL, n = 43).


RESULTS
The LDLox and hs-CRP levels increased in the high-LDL group (2.7- and 3.7- fold, respectively), whereas the intermediate and high-LDL groups had higher LDLoxAB (2.2- and 3.1-fold) when compared to low-LDL group (p < 0.05). Similarly, SOD activity, the atherogenic index (AI) and protein oxidation were also higher in the intermediate (1.3-, 1.3- and 1.2-fold) and high-LDL (1.6-, 2.3- and 1.6-fold) groups when compared to the low-LDL group (p < 0.05). Lipid oxidation and SOD/TrxR-1 ratio increased only in the high-LDL group (1.3- and 1.6-fold) when compared to the low-LDL group (p < 0.05). The SOD/TrxR-1 ratio was positively correlated to TBARS (r = 0.23, p < 0.05), LDLox (r = 0.18, p < 0.05), LDLoxAB (r = 0.21, p < 0.05), LDL (r = 0.19, p < 0.05) and AI (r = 0.22, p < 0.05). PON1 and TrxR-1 activities were similar among groups.


CONCLUSIONS
Some oxidative events initiate when LDL levels are clinically acceptable. Moreover, hypercholesterolemic patients have an imbalance in SOD and TrxR-1 activities that is positively associated to LDL oxidation.
Department of Biochemistry, Graduate Program on Biological Sciences/Biochemistry, Institute of Health Basic Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Paula Rossini
PR
Augusti
Amanda Roggia
AR
Ruviaro
Andréia
A
Quatrin
Sabrina
S
Somacal
Greicy Michelle Marafiga
GM
Conterato
Juliana Tanara
JT
Vicentini
Marta Medeiros Frescura
MM
Duarte
Tatiana
T
Emanuelli
D000328:Adult; D000368:Aged; D043303:Aryldialkylphosphatase / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000201:enzymology* / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000097:blood*; D054481:Thioredoxin Reductase 1 / Q000097:blood*
D001323:Autoantibodies; D015415:Biomarkers; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein; D013482:Superoxide Dismutase; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human