Naslov
The opposite effects of simvastatin and atorvastatin on serum and liver paraoxonase activity in normolipemic rats

Autori
Macan, Marija ; Bradamante, Vlasta ; Vrkić, Nada ; Radić, Božica ; Lucić Vrdoljak, Ana ; Konjevoda, Paško

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstracts of the 5th Croatian Congress of Pharmacology and 2th Congress of Croatian Physiological Society ; u: Periodicum Biologorum. Supplement (ISSN 0353-9164) 109 (2007) (S1) / - , 2007, 115-115

Skup
5th Croatian Congress of Pharmacology and 2th Congress of Croatian Physiological Society

Mjesto i datum
Osijek, Hrvatska, 19.09.2007. - 22.09.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Simvastatin; Atorvastatin; Serum paraoxnase; Liver paraoxonase; Rats
(Simvastatin; Atorvastatin; Serum paraoxnase; Liver paraoxonase; Rat)

Sažetak
Paraoxonase (PON1) is serum esterase which is synthesized in the liver, and has unknown physiological function. PON1 has a clinical importance, because it plays a protective role in case of organophosphates intoxication. According to the many experimental data PON1 is included in lipid metabolism. It is suggested that PON1 is associated with high density (HDL)-cholesterol, and that HDL stimulates PON1 secretion from the liver. Also it has been shown that PON1 prevents the formation of oxidized LDL and protects phospholipids in HDL from oxidation. Hyperlipidemia and oxidative stress reduce PON1 activity. It has been suggested that statins which are used for the treatment of hyperlipidemia, can decrease or increase serum PON1 activity, and that this is the consequence of another, independent effect of statins, i.e. their antioxidant action. Because the most of these results were goten from human and animals in conditions of altered lipid’ s metabolism, it was of interest to investigate the effects of simvastatin (SIMV) and atorvastatin (ATOR) on PON1 activity in serum and liver of normolipidemic rats. Material and Methods. Forty six male Wistar rats (weight 170-200 g), were divided in two control groups (n=7 each) and four experimental groups. Two experimental groups were on SIMV treatment and the remaining two groups (n=8) on ATOR treatment. Both agents were given orally in the same doses (10 and 50 mg/kg/day) and for the period of 3 weeks. At the end of drug treatment animals from all groups were sacrificed. PON1 activity in plasma and liver was measured by the spectrophotometric method using synthetic diethyl-p-nitrophenyl phosphate (paraoxon) and moderator CaCl2. The activity toward paraoxon was determined by measuring the initial rate of substrate hydrolysis to p- nitrophenol. The plasma or liver enzyme activity was calculated from E405 of p-nitrophenol and expressed as μ mol of substrate hydrolysed per min per ml of serum or g of the tissue wet weight. Concentration of HDL-cholesterol and TGs in plasma were determined by enzymatic colorimetric methods and expressed as mmol/L of plasma. Data were analyzed by Kruskal-Wallis test and results were considered as significant with p<0.05. Results. SIMV administration in both doses reduced serum PON1 activity by 21%. Low dose of SIMV decreased liver PON1 activity by 37% and high dose by 56%. But, in any case the decrease of PON1 activity was not significant. High dose of ATOR caused the increase of serum PON1 activity by 18% (p<0.05), and both doses caused the increase of liver PON1 activity by 28% (10 mg/kg/day), and 43% (50 mg/kg/day) (p<0.05). Both doses of SIMV had no significant influence on plasma HDL-cholesterol. In opposite, HDL- cholesterol concentration was significantly increased after low dose of ATOR. Both drugs didn’ t markedly reduce plasma triglycerides. Conclusion. Our results have shown that SIMV and ATOR have the opposite effects on PON1 activity. It was mentioned that ATOR shows antioxidant action. We suggest that ATOR reduces oxidative stress in a grater manner, and that the significant increase in PON1 activity by ATOR may be the result of its better antioxidant action in comparison with that of SIMV. Consequently, ATOR does not cause the inactivation in PON1 activity, than its increase.

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

POVEZANOST RADA