H. Alzuhair et al., EFFICACY OF SIMVASTATIN AND PUMPKIN-SEED OIL IN THE MANAGEMENT OF DIETARY-INDUCED HYPERCHOLESTEROLEMIA, Pharmacological research, 35(5), 1997, pp. 403-408
Pumpkin-seed oil (PSO), a natural supplement rich with antioxidants an
d polyunsaturated fatty acids (PUFAs), was given in combination with s
imvastatin, as antihypercholesterolemic drug, to high cholesterol-fed
rabbits, for three weeks. In comparison with normal rabbits, a signifi
cant increase of the aortic contractile response to norepinephrine was
observed which could be attributed to endothelium dysfunction, In add
ition, serum levels of total lipids, triacylglycerols, total cholester
ol and low density lipoprotein-cholesterol (LDL-C) were increased whil
e phospholipids and high density lipoprotein-cholesterol (HDL-C) were
decreased in hypercholesterolemic rabbits. These changes could be rela
ted to the predominance of LDL and oxidized-LDL particles caused by hi
gh levels of reactive oxygen species during hypercholesterolemia (HC).
Treatment with simvastatin modulated most of the altered parameters a
ffected during HC that might be, in part, due to inhibition of cholest
erol biosynthesis. While concomitant administration of simvastatin and
PSO succeeded to cause marked reduction of the aortic contractile res
ponse to norepinephrine and to normalize the most adverse effects obse
rved during HC. These effects were explained by the potentiating effec
ts of simvastatin with antioxidants and essential fatty acids in PSO.
On the contrary, serum activities of aminotransferases and creatine ph
osphokinase were increased with simvastatin treatment but not with the
combination therapy in hypercholesterolemic rabbits.