Effects of simvastatin on alveolar regeneration and its relationship to exposure in mice with dexamethasone-induced emphysema

Abstract

In the present study, the relationship between systemic exposure of simvastatin (SV) hydroxy acid (SV-acid), an active form of SV, and its alveolar regeneration rates was investigated using emphysema model mice created by postnatal treatment of dexamethasone. In a model with young animals, the mice were treated with SV for 10 d from postnatal day 42. Similar alveolar regeneration with a % mean linear intercept (Lm) recovery of 60 to 70% by histochemical observation was observed in mice after intraperitoneal administration at dose in the range of 4-100 μg/mouse. The % Lm recovery after oral administration of 20 μg/mouse was comparable with that after intraperitoneal administration at a dose of 4 μg/mouse, when their exposure of SV-acid was almost similar in both treated groups. Regardless of the route of administration, the recovery can depend on the exposure level of SV-acid, and to the maximum was about 60-70%. On the other hand, in a model with adult animals, the mice were intraperitoneally administrated SV at a dose of 4 μg/mouse for 10 d from postnatal day 152. Compared to young animals, less % Lm recovery was observed in adult mice even their systemic exposures of SV-acid were similar.