Effects of Simvastatin on Alveolar Regeneration and Its Relationship to Exposure in Mice with Dexamethasone-Induced Emphysema.
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 % Lmrecovery 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 % Lmrecovery was observed in adult mice even their systemic exposures of SV-acid were similar.
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science.
Shihomi
S
Hirooka
Misaki
M
Ueno
Satoko
S
Fukuda
Atsushi
A
Miyajima
Takashi
T
Hirota
D000818:Animals; D003907:Dexamethasone / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D011656:Pulmonary Emphysema / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D003907:Dexamethasone; D019821:Simvastatin