Zingerone ameliorates oxidative stress and inflammation in bleomycin-induced pulmonary fibrosis: modulation of the expre
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ORIGINAL ARTICLE
Zingerone ameliorates oxidative stress and inflammation in bleomycin-induced pulmonary fibrosis: modulation of the expression of TGF-β1 and iNOS Huseyin Gungor 1 & Mehmet Ekici 2 & Mehmet Onder Karayigit 3 & Nergiz Hacer Turgut 4 Emre Arslanbas 1,5
&
Haki Kara 1 &
Received: 5 January 2020 / Accepted: 22 April 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with limited treatment options. Zingerone found in ginger (Zingiber officinale L.) has many pharmacological effects, especially antiinflammatory and antioxidant activity. However, the effect of zingerone on pulmonary fibrosis (PF) is not fully known. The aim of this study was to investigate the effect of zingerone on bleomycin (BLM)-induced PF and its underlying mechanisms. Wistar-albino rats were given single dose of BLM (5 mg/kg, intratracheal) or vehicle (saline). In treatment groups, zingerone (50 and 100 mg/kg, p.o.) was administered orally for 14 days after BLM administration. Rats and lung tissue were weighed to determine lung index. Antioxidant, antiinflammatory effects, and hydroxyproline content of zingerone were determined by ELISA method. Pulmonary inflammation, collagen deposition, and fibrosis score were determined with Hematoxylin-Eosin (HxE) and Masson’s trichrome staining. Transforming growth factorbeta 1 (TGF-β1) and inducible nitric oxide synthase (iNOS) expressions were detected immunohistochemically. BLM administration increased lipid peroxidation (MDA) and decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. In addition, BLM caused increased levels of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF) and accumulation of collagen bundles. Zingerone administration decreased collagen accumulation, TNF-α and IL-1β levels, MDA level, TGF-β1, and iNOS expression and increased SOD and GPx activity. Histopathological findings supported the results. These results show that zingerone (50 and 100 mg/kg) at both doses significantly contributes to healing of PF by improving inflammation, oxidative stress, and histopathological alterations and by affecting TGF-β1 and iNOS signaling pathways. Keywords Zingerone . Pulmonary fibrosis . Antifibrotic effect . Transforming growth factor-beta 1 (TGF-β1) . Inducible nitric oxide synthase (iNOS)
* Nergiz Hacer Turgut [email protected] 1
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Cumhuriyet University, 58140 Sivas, Turkey
2
Department of Physiology, Faculty of Veterinary Medicine, Cumhuriyet University, 58140 Sivas, Turkey
3
Department of Pathology, Faculty of Veterinary Medicine, Cumhuriyet University, 58140 Sivas, Turkey
4
Department of Pharmacology, Faculty of Pharmacy, Izmir Katip Celebi University, 35620 Izmir, Turkey
5
Present address: Department of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ataturk University, 25240 Erzurum, Turkey
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