Sinapic acid ameliorates bleomycin-induced lung fibrosis in rats
Authors: Altaf Khan
Fahad I Al-Jenoobi
Abdullah M Al-Mohizea
Abdul Ahad
Ajaz Ahmad
Naushad Ali
Mushtaq Ahmad Ansari
Mohammad Raish
Journal: Biomedicine & Pharmacotherapy (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Extracellular matrix deposition; Inflammation; Lung fibrosis; Sinapic acid.
Affiliations: Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address: ., Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Quality Research Unit, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

Abstract:  Background: Pulmonary fibrosis is a multifaceted disease with high mortality and morbidity, and it is commonly nonresponsive to conventional therapy. Purpose: We explore the possible discourse of sinapic acid (SA) against the prevention of bleomycin (BLM)-instigated lung fibrosis in rats through modulation of Nrf2/HO-1 and NF-κB signaling pathways. Design/methods: Lung fibrosis was persuaded in Sprague-Dawley rats by a single intratracheal BLM (6.5 U/kg) injection. Then, these rats were treated with SA (10 and 20 mg/kg, p.o.) for 28 days. The normal control rats provided saline as a substitute of BLM. The lung function and biochemical, histopathological, and molecular alterations were studied in serum, bronchoalveolar lavage fluid (BALF), and the lungs tissues. Results: SA treatment significantly restored BLM-induced alterations in body weight index and serum biomarkers [lactate dehydrogenase (LDH) and alkaline phosphatase (ALP)]. SA (10 and 20 mg/kg) treatment appeared to show a pneumoprotective effect through upregulation of antioxidant status, downregulation of inflammatory cytokines and MMP-7 expression, and reduction of collagen accumulation (hydroxyproline). Nrf2, HO-1, and TGF-β expression was downregulated in BLM-induced fibrosis model, while the reduced expression levels were significantly and dose-dependently upregulated by SA (10 and 20 mg/kg) treatment. We demonstrated that SA ameliorates BLM-induced lung injuries through inhibition of apoptosis and induction of Nrf2/HO-1-mediated antioxidant enzymes via NF-κB inhibition. The histopathological findings also revealed that SA treatment (10 and 20 mg/kg) significantly ameliorated BLM-induced lung injury. Conclusion: The present results showed the ability of SA to restore the antioxidant system and to inhibit oxidative stress, proinflammatory cytokines, extracellular matrix, and TGF-β. This is first report demonstrating that SA amoleriates BLM induced lung injuries through inhibition of apoptosis and induction of Nrf2 and HO-1 mediated antioxidant enzyme via NF-κB inhibition. The histopathological finding reveals that SA treatment (10 and 20 mg/kg) significantly ameliorates BLM induced lung injuries. 

Retracted: No

PubPeer comments:
 Would the authors be so kind as to post the original uncropped scans of the western blot in Figure 5B? The upper band appears very different from the images in the rest of the figure. *** ![file] *** ![file] ,