Natural isoprenoids enhance cholesterol-lowering effect of statins in human liver cells

RODENAK-KLADNIEW BORIS; POLO MÓNICA; GARCÍA DE BRAVO MARGARITA

Mendoza

Congreso; XLVIII Reunión Anual de SAIB; 2012

SAIB

Cholesterol (C) excess in blood produces coronary diseases which are the main cause of world death. Statins (ST), as simvastatin (SV), are competitive inhibitors of HMG-CoA reductase widely used as hypocholesterolemic drugs, which occasionally cause diseases such as hepatic dysfunction and weakness. Natural isoprenoids (NI) as linalool (LN) and cineole (CN) are hydrocarbons derived from the mevalonate pathway in plants capable of decreasing cholesterol synthesis (CS) by different mechanisms than statins. The possibility to diminish effective doses of ST by dietary supplement with NI arises as an interesting therapeutic alternative. We studied the action of the combination of LN, CN and SV on CS and C content (CC) in HepG2 cells. Cells were treated with LN, CN and SV, alone or combined in pairs, at concentrations which did not inhibit cell proliferation. CC and 14C-acetate incorporation into C were determined. Our results showed a decrease in CS and CC when cells were treated with LN, CN, SV and their combinations. R index was calculated to determine if the combinations decrease additively (R=1) or synergistically (R>1) the CS and CC. We found values of R>1 in all combinations for CS while the combination LN-SV had an additive effect on the lowering of CC. Our results suggest a possible benefit and future uses of ST and NI combined in the treatment of hypercholesterolemic diseases.