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.

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.

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].

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

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].

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

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

G-2 [0.5 mg/kg/day G-2 [0.5 mg/kg/day atorvastatin group]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

G-2 [0.5 mg/kg/day atorvastatin group]

Minimal increases in the collagen fibrils structure were observed in the interstitial areas

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

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

G-3 [1 mg/kg/day atorvastatin group]

A widespread increase of collagen fibrils was seen in the intra-alveolar septum

G-3 [1 mg/kg/day atorvastatin group]

Chromatin condensation, atrophic appearance, cell shrinkage, and cytoplasmic vacuolizations were discerned in the ATII cells

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.

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.