2016Jundishapur Journal of Natural Pharmaceutical ProductsOpen access

Ameliorative Effects of Atorvastatin on Bleomycin-Induced Pulmonary Fibrosis in Rats

Ali Asghar Hemmeti, Mohammad Rahim Zerafatfard, Mehdi Goudarzi, Mohammad Javad Khodayar, Annahita Rezaie, Mohammadreza Rashidi Nooshabadi, Milad Kiani

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Abstract

Background: Pulmonary fibrosis is an idiopathic and chronic inflammatory interstitial lung disease, with a negligible response to available medical therapies and potentially fatal prognosis. Statins (3-hydroxy-3-methylglutaryl-coenzyme A [HMG CoA] reductase inhibitors) have broad pleiotropic properties and are used to treat multiple diseases. Objectives: The purpose of this study was to investigate the effect of different doses of atorvastatin (10, 20, and 40 mg/kg) on bleomycin (BLM)-induced pulmonary fibrosis in rats. Methods: Thirty female 8-wk-old Sprague Dawley rats, weighing 200 ± 20 g, were randomly divided into five experimental groups. Group 1 (control) received saline intratracheally (IT), group 2 received a single dose of BLM (7.5 UI/kg/mL, IT) on day 7 and no treatment, and groups 3 - 5 received atorvastatin orally at doses of 10, 20, and 40 mg/kg, respectively, one week before and again three weeks after BLM administration. The rats were sacrificed 21 days after the administration of BLM. Blood and lungs were collected for plasma malondialdehyde (MDA), lung hydroxyproline, and histopathological examination. Results: The results showed that lung hydroxyproline and plasma MDA levels were significantly reduced in the atorvastatin-treated groups, especially the 40 mg/kg group, compared to the BLM untreated group (P < 0.05). Furthermore, atorvastatin prevented infiltration of inflammatory cells, proliferation of fibroblasts, and alveolar thickening due to BLM. Conclusions: Atorvastatin may play a protective role in pulmonary fibrosis, with its effects mediated via the station’s antioxidant and anti-inflammatory properties. Atorvastatin may be a potential agent for the treatment of lung injury and fibrosis.

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Background: Pulmonary fibrosis is an idiopathic and chronic inflammatory interstitial lung disease, with a negligible response to available medical therapies and potentially fatal prognosis. Statins (3-hydroxy-3-methylglutaryl-coenzyme A [HMG CoA] reductase inhibitors) have broad pleiotropic properties and are used to treat multiple diseases. Objectives: The purpose of this study was to investigate the effect of different doses of atorvastatin (10, 20, and 40 mg/kg) on bleomycin (BLM)-induced pulmonary fibrosis in rats. Methods: Thirty female 8-wk-old Sprague Dawley rats, weighing 200 ± 20 g, were randomly divided into five experimental groups. Group 1 (control) received saline intratracheally (IT), group 2 received a single dose of BLM (7.5 UI/kg/mL, IT) on day 7 and no treatment, and groups 3 - 5 received atorvastatin orally at doses of 10, 20, and 40 mg/kg, respectively, one week before and again three weeks after BLM administration. The rats were sacrificed 21 days after the administration of BLM. Blood and lungs were collected for plasma malondialdehyde (MDA), lung hydroxyproline, and histopathological examination. Results: The results showed that lung hydroxyproline and plasma MDA levels were significantly reduced in the atorvastatin-treated groups, especially the 40 mg/kg group, compared to the BLM untreated group (P < 0.05). Furthermore, atorvastatin prevented infiltration of inflammatory cells, proliferation of fibroblasts, and alveolar thickening due to BLM. Conclusions: Atorvastatin may play a protective role in pulmonary fibrosis, with its effects mediated via the station’s antioxidant and anti-inflammatory properties. Atorvastatin may be a potential agent for the treatment of lung injury and fibrosis.

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Available abstract

Background: Pulmonary fibrosis is an idiopathic and chronic inflammatory interstitial lung disease, with a negligible response to available medical therapies and potentially fatal prognosis. Statins (3-hydroxy-3-methylglutaryl-coenzyme A [HMG CoA] reductase inhibitors) have broad pleiotropic properties and are used to treat multiple diseases. Objectives: The purpose of this study was to investigate the effect of different doses of atorvastatin (10, 20, and 40 mg/kg) on bleomycin (BLM)-induced pulmonary fibrosis in rats. Methods: Thirty female 8-wk-old Sprague Dawley rats, weighing 200 ± 20 g, were randomly divided into five experimental groups. Group 1 (control) received saline intratracheally (IT), group 2 received a single dose of BLM (7.5 UI/kg/mL, IT) on day 7 and no treatment, and groups 3 - 5 received atorvastatin orally at doses of 10, 20, and 40 mg/kg, respectively, one week before and again three weeks after BLM administration. The rats were sacrificed 21 days after the administration of BLM. Blood and lungs were collected for plasma malondialdehyde (MDA), lung hydroxyproline, and histopathological examination. Results: The results showed that lung hydroxyproline and plasma MDA levels were significantly reduced in the atorvastatin-treated groups, especially the 40 mg/kg group, compared to the BLM untreated group (P < 0.05). Furthermore, atorvastatin prevented infiltration of inflammatory cells, proliferation of fibroblasts, and alveolar thickening due to BLM. Conclusions: Atorvastatin may play a protective role in pulmonary fibrosis, with its effects mediated via the station’s antioxidant and anti-inflammatory properties. Atorvastatin may be a potential agent for the treatment of lung injury and fibrosis.

Key concepts: Atorvastatin, Medicine, Hydroxyproline, Bleomycin, Pulmonary fibrosis, Malondialdehyde, Saline, Fibrosis

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