engleski

The effects of simvastatin and fenofibrate on plasma, liver and braincholinesterase in hyperlipidemic rats

Background: It was suggested that statins exerted their protective effect against Alzheimer disease (AD) due to inhibition of cholinesterase (ChE) activity. Results of some nonclinical and clinical studies have shown that statins either do not influence or decrease enzyme catalytic activity. Our previous studies showed that simvastatin increased plasma and liver ChE activity in normolipidemic rats. In respect to these findings we studied influence of simvastatin (SIMV) and fenofibrate (FENO) on ChE activity in hyperlipidemic rats. Methods: Twenty-one male hyperlipidemic Zucker rats were divided into one control and two experimental groups. One experimental group was on SIMV treatment (50 mg/kg/day) and another on FENO treatment (30 mg/kg/day). Both agents were given orally for 3 weeks, as well as saline for control group. Animals were sacrificed 24 hours after the last dose. Blood samples were obtained directly from heart. Liver and brain tissue were rinsed with saline. ChE activity was determined by Ellman’s spectrophotometric method using butyrylthiocholine and acetylthiocholine as substrates. In liver tissue the ChE activity was measured with and without ethopropazine hydrochloride. Enzyme activities were expressed as μmol of substrate hydrolysed per min per ml of serum or g of tissue. Data were analyzed using ANOVA and Dunnett's test. Results were considered as significant with p<0.05. Results: Plasma ChE activity was significantly increased in both experimental groups when butyrythiocholine (SIMV 0.317±0.038 ; FENO 0.404±0.042 vs. control 0.164±0.010) and acetythiocholine were used (SIMV 0.667±0.096 ; FENO 0.788±0.118 vs. control 0.434±0.025). Liver ChE activity was significantly increased in both experimental groups when acetythiocholine was used (SIMV 5.21±0.304 ; FENO 5.91±0.452 vs. control 3.70±0.473), but using butyrythiocholine significant increase was measured only with SIMV (SIMV 0.773±0.147 vs. control 0.439±0.129). Brain ChE activity was increased in both experimental groups. Significant increase in the groups was measured using butyrythiocholine (SIMV 0.0823±0.0062 ; FENO 0.0795±0.0032 vs. control 0.0714±0.0026). With acetythiocholine significant increase happened only after administration of SIMV (SIMV 0.319±0.037 vs. control 0.274±0.021). Conclusion: Our results showed that simvastatin and fenofibrate increased plasma, liver and brain ChE activity in hyperlipidemic rats. We suggest that protective effect of statins against AD is not the consequence of cholinesterase inhibition.

simvastatin ; fenofibrate ; cholinesterase ; hyperlipidemic rats

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