High lovastatin doses combined with hypercholesterolemic diet induce hepatic damage and are lethal to the CD-1 mouse

The addition of 1% lovastatin (LVT) to hypercholesterolemic diets [1% cholesterol or 1% cholesterol plus 0.1% sodium deoxycholate (HD)] induced hepatic damage and was lethal to CD-1 mice in the first days of treatment; the females were more resistant than males. LVT or HD administered alone was harmless to male or female mice. After a 3-day treatment all groups that received LVT (1%, 0.1% or 0.05%) plus HD showed a higher percentage of liver weight, with respect to whole body weight. Cholesterol serum levels increased in males with HD, but remained low in female mice. In the liver, total lipids and cholesterol levels increased in male mice with HD, but cholesterol remained unchanged in females. The addition of LVT to HD prevented the increase of serum and liver cholesterol levels in male mice. These results allow us to propose the CD-1 male-mouse as a model to evaluate the toxicity of LVT or other vastatins.