Comparative toxicity of high doses of vastatins currently used by clinicians, in CD-1 male mice fed with a hypercholesterolemic diet.
The CD-1 male-mouse model was employed to evaluate comparatively the toxicity of four vastatins (VTS) currently used in clinical medicine: lovastatin (LVT), simvastatin (SVT), pravastatin (PVT) and fluvastatin (FVT). Each vastatin was used orally in doses of 500 mg/Kg body weight/day, in animals with a hypercholesterolemic diet (HD) 5 days, or with a control diet (CD) 30 days. The association of high doses of VTS + HD produced a significant increase in liver weight and liver weight to body weight ratio in animals with SVT and FVT. Cholesterol (Chol) and triacylglycerols (TAG) in the liver increased significantly with FVT but not with the other VTS; Chol increased and TAG decreased in serum very significantly with FVT and SVT. The serum aminotransferases increased quite significantly with FVT but not with other VTS. In the experiment with high doses of VTS + CD, the animals receiving SVT or FVT showed a moderate loss of body weight. Liver weight and liver weight to body weight ratios were similar among all groups. Liver Chol showed a significant decrease with all VTS. Serum Chol decreased moderately with LVT and FVT. TAG in serum and liver showed a moderate decrease with all VTS. The serum aminotransferases were not modified by any vastatin. Our results indicate that high doses of VTS in male mice with a hypercholesterolemic diet result in a decreasing toxicity as follows: FVT>SVT>LVT>PVT.
Díaz-Zagoya
J C
JC
Departamento de Bioquímica, Facultad de Medicina, UNAM, Ciudad Universitaria, DF, México. zagoya@servidor.unam.mx
Asenjo-Barrón
J C
JC
Cárdenas-Vázquez
R
R
Martínez
F
F
Juárez-Oropeza
M A
MA
D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000032:analysis / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000633:toxicity; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D007211:Indoles / Q000008:administration & dosage / Q000633:toxicity; D008055:Lipids / Q000032:analysis / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008148:Lovastatin / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D017035:Pravastatin / Q000008:administration & dosage / Q000633:toxicity; D019821:Simvastatin / Q000008:administration & dosage / Q000633:toxicity; D013997:Time Factors; D000637:Transaminases / Q000097:blood; D014280:Triglycerides / Q000032:analysis / Q000097:blood
D000924:Anticholesteremic Agents; D002791:Cholesterol, Dietary; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008055:Lipids; D014280:Triglycerides; D000077340:Fluvastatin; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin; D000637:Transaminases; D017035:Pravastatin