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. 2009 Oct;70(5):366–376. doi: 10.1016/j.curtheres.2009.10.003

Effects of atorvastatin on smoking-induced alveolar injury in rat lungs

Tekin Yildiz 1,*, M Serhan Tasdemir 2, Selcuk Tunik 2, Gungor Ates 1, Selahaddin Tekes 3, Iskender Kaplanoglu 2, Fusun Topcu 1, Murat Akkus 2
PMCID: PMC3967291  PMID: 24683245

Abstract

Background: Smoking is one of the most serious health care issues worldwide, as one third to one half of all people who smoke eventually use tobacco habitually. Chronic smoke exposure causes airway and lung parenchymal inflammation and the destruction of alveolar cell walls. Statins may have anti-inflammatory effects that would play a role in preventing the cellular damage associated with smoking.

Objective: The aim of this study was to investigate whether atorvastatin protects against smoking-induced inflammation in alveolar epithelial type I (ATI) and type II (ATII) cells in the lungs of rats.

Methods: Adult male albino Wistar rats (200–250 g) were randomly divided into 3 groups and exposed to cigarette smoke 8 hours per day for 15 days. During that 15-day period, the 2 treatment groups received atorvastatin 0.5 or 1.0 mg/kg/d in 2 mL of methyl cellulose solution and the control group received 2 mL of methyl cellulose solution alone, all via nasogastric catheter. After the 15 days, the lungs were excised and the tissues were examined by transmission electron microscopy.

Results: Thirty rats were divided into 3 groups of 10 rats each. All rats survived the 15 days. In the atorvastatin 0.5-mg group, no changes were found in the ATI cells or in the blood-air barrier. In the atorvastatin 1.0-mg group, we observed hyperplasia in the common basal membranes. Hypertrophy, mitochondrial crystolysis (MC), and intracytoplasmic edema (ICE) were detected in the ATI cells in the 1.0-mg group, while chromatin condensation, atrophic appearance, cell shrinkage, and cyto-plasmic vacuolization were observed in the ATII cells. The rough endoplasmic reticulum (rER) tubules of the ATII cells appeared spiral-shaped. In the control group, minimal ICE was detected in the ATI cells. However, microvillus deformation, pseu-dopod formation, edema, mitochondrial swelling, and MC were observed in the ATII cells. We also observed MC, several pinocytic vesicles, and normal rER tubules in the endothelial cells of the control group.

Conclusions: The administration of atorvastatin 0.5 mg/kg/d was associated with some attenuation of lung injury caused by smoke inhalation in these rat lungs. However, atorvastatin 1.0 mg/kg/d was associated with lung damage. Future studies are needed to evaluate the dose-response relationship of atorvastatin to smoking-induced alveolar damage.

Key words: lung, atorvastatin, ultrastructural changes, rat

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