Beneficial effects of diclofenac therapy on serum lipids, oxidized low-density lipoprotein and antioxidant defenses in rats

To study the effects of diclofenac, a nonselective nonsteroidal anti-inflammatory drug (NSAID), on lipid profile, oxidized low-density-lipoprotein (Ox-LDL), serum antioxidant defenses and markers of oxidative stress, male Wistar rats were divided into two groups ( n = 10): (C) receiving intramuscula...

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Published in:Life sciences (1973) 2008-04, Vol.82 (15), p.892-898
Main Authors: Curcelli, Emilio C., Muller, Sergio S., Novelli Filho, José Luiz V.B.
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - therapeutic use
Antioxidants - metabolism
Biomarkers - metabolism
Cholesterol - blood
Diclofenac
Diclofenac - therapeutic use
Dyslipidemias - blood
Dyslipidemias - drug therapy
Lipid Peroxides - blood
Lipids - blood
Lipoproteins, LDL - blood
Male
NADP - blood
NSAID
Ox-LDL
Oxidative stress
Oxidative Stress - physiology
Rats
Rats, Wistar
Superoxide dismutase
Superoxide Dismutase - blood
Triglycerides - blood
Weight Gain - drug effects
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Summary:To study the effects of diclofenac, a nonselective nonsteroidal anti-inflammatory drug (NSAID), on lipid profile, oxidized low-density-lipoprotein (Ox-LDL), serum antioxidant defenses and markers of oxidative stress, male Wistar rats were divided into two groups ( n = 10): (C) receiving intramuscularly a single daily dose of saline (NaCl 0.9%), and (AI) receiving intramuscularly a single daily dose of 10 mg/kg diclofenac sodium (C 14H 10Cl 2NNaO 2). After 28 days diclofenac-treated rats had lower Ox-LDL, apoprotein B (apo-B), apo-B/LDL-cholesterol and lipid hydroperoxide than C. Total antioxidant substances and superoxide dismutase were increased in diclofenac-treated rats, while no significant changes were observed in catalase, glutathione peroxidase and nitric oxide. A perincubation test done to examine the possibility of mechanism-based activation showed that diclofenac had no effect on maximal superoxide dismutase velocity, but significantly reduced the Michaelis–Menten ( K M) constant, indicating that diclofenac induced SOD activation increasing substrate linkage affinity to the enzyme-catalytic site. In conclusion, diclofenac had beneficial effects decreasing Ox-LDL and improving antioxidant defense. It appears that the application of this agent may be feasible and beneficial for serum antioxidant protection, which certainly would bring new insights on dyslipidemia control.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2008.02.004