2.  We conducted this study to establish whether statins have protective anti- inflammatory effects against inflammation induced by cigarette smoke in rat lung cells, and in particular, the alveoli epithelial types I and II.

3.  Thirty mature male Wistar albino rats were used in this experimental study.  The rats were divided into three groups of 10 rats each.  All rats were provided standard pelleted food and tap water ad libitum, and were kept at 20 ± 2ºC under a 12 h light/12 h dark light regimen in a stainless steel cage.

4.  Thirty rats were divided into three groups and exposed to 20% smoke from 10 standard test cigarettes daily for 15 days.  The group-1 [G-1] smoke-exposed rats were used as controls, and  Groups 2 and 3 [G-2 and G-3] were treated with 0.5 mg/kg/day or 1.0 mg/kg/day atorvastatin, respectively.  The lung tissues were examined by transmission electron microscopy [TEM] [JEOL 1010, JEOL Ltd., Tokyo, Japan].

5.  The study was approved by the institutional review board on animal experimentation of Dicle University, Diyarbakir, Turkey [2006-TF-059].

6.  The rats were euthanized by ether anesthesia.  The lungs were extirpated and fixed in 2.5% phosphate-buffered glutaraldehyde for histopathological evaluation.  Samples of semi-thin cross sections of the lung tissues were prepared with an ultramicrotome, stained with toluidine blue, and stored in copper grids.  The tissues that were stained with lead acetate and uranyl citrate were screened by TEM [JEOL 1010, JEOL Ltd., Tokyo, Japan].

8.  G-1 [cigarette smoke control group; no atorvastatin]  Minimal intracytoplasmic edema [ICE] and partial separation were observed in the ATI nuclear membranes.  Mitochondrial crystolysis [MC] was detected in the capillary endothelial cells, while several pinocytic vesicles were seen in the capillary endothelial cells.  Furthermore, the rER tubulae of the capillary endothelial cells were of normal shape and size

9.  G-1 [cigarette smoke control group; no atorvastatin]  Microvillus deformation, pseudopod formation, edema, mitochondrial swelling, and MC were detected in the ATII cells.  All intracellular lipid droplets were clear, the mature lamellar body was absent, and the rER tubulae were inactive

10.  G-2 [0.5 mg/kg/day atorvastatin group]  No changes were detected in the G-2 ATI cells, blood–air barrier, or the cellular organelles.  The common basal membranes of the ATI and capillary endothelial cells were normal

11.  G-2 [0.5 mg/kg/day atorvastatin group]  Minimal increases in the collagen fibrils structure were observed in the interstitial areas

12.  G-2 [0.5 mg/kg/day atorvastatin group]  Upon examination of the ATI and ATII cells located beneath the collagen matrix, we detected only minimal changes in the mitochondriae and microvillae in the ATII cells.  The lysosomal structure was approximately normal-shaped, and minimal intracellular edema was detected in the ATI cells

13.  G-3 [1 mg/kg/day atorvastatin group]  Hyperplasia of the common basal membrane of the ATI and capillary endothelial cells was observed.  Hypertrophy, MC, and intracytoplamsic edema were detected in the ATI cells

14.  G-3 [1 mg/kg/day atorvastatin group]  A widespread increase of collagen fibrils was seen in the intra-alveolar septum

15.  G-3 [1 mg/kg/day atorvastatin group]  Chromatin condensation, atrophic appearance, cell shrinkage, and cytoplasmic vacuolizations were discerned in the ATII cells

16.  G-3 [1 mg/kg/day atorvastatin group]  The rER tubulae were spiral-shaped in the ATII cells [Figure 3d], closely resembling cells undergoing apoptosis.

17.  The protective and/or hazardous effects of statins in lung cells may be dose- dependent.  Moreover, the administration of high dose atorvastatin can cause apoptosis in cells inflamed by cigarette smoke.