Differential effects of statins on plasma and brain cholinesterase activities in chicks

Abstract

Statins used to treat dyslipidemia may differentially modulate cholinesterase (ChE) activity impacting neuronal function. This study examines the effects of three statins (atorvastatin, fluvastatin, and simvastatin) on plasma and brain ChE activities and cholesterol levels in a chick model of 7-14 days old. Chicks were dosed orally with single doses of each statin at 50, 100, and 200mg/kg or repeated doses at 100mg/kg/day for 14 consecutive days. Plasma and whole brain ChE activities were measured electrometrically, whereas cholesterol levels were measured using a commercial colourimetric kit. In vitro ChE inhibition by the statins was initiated at 37°C for 10 mins. Data were statistically analysed using analysis of variance followed by the least significant difference test. Atorvastatin and fluvastatin did not significantly affect plasma ChE activities 2 hours after the oral administration, whereas simvastatin at 100 and 200mg/kg significantly increased (28% and 16%, respectively) plasma ChE activity. Repeated oral doses of the statins did not significantly affect plasma ChE activity. However, only simvastatin significantly decreased whole brain ChE activity by 33%. Repeated treatments with the three statins significantly reduced cholesterol levels in the plasma but not in the whole brain. The three statins inhibited in vitro plasma and whole brain ChE activities by 10-33% and 8-43%, respectively. The results suggested that the statins differentially modulated ChE activity in vivo and in vitro in chicks. Additional in vivo studies are warranted on statin effects on ChE activity in different brain regions of animal models.