Hesperidin ameliorates bleomycin-induced experimental pulmonary fibrosis via inhibition of TGF-β1/Smad3/AMPK and IκBα/NF-κB pathways
| dc.contributor.author | Zhou, Zheng | |
| dc.contributor.author | Kandhare, Amit D. | |
| dc.contributor.author | Kandhare, Anwesha A. | |
| dc.contributor.author | Bodhankar, Subhash L. | |
| dc.date.accessioned | 2020-03-06T12:30:36Z | |
| dc.date.available | 2020-03-06T12:30:36Z | |
| dc.date.issued | 2019-08-29 | |
| dc.description.abstract | Bleomycin (BLM) is a chemotherapeutic agent which is associated with Idiopathic pulmonary fibrosis (IPF) due to its chronic administration. Hesperidin, a bioflavonoid has been reported to possess antioxidant, anti-inflammatory, wound healing, and antiapoptotic potential. To eval uate the therapeutic potential of hesperidin against BLM-induced pulmonary fibrosis and deciph er its possible mechanism of action. Intraperitoneal administration of BLM (6 IU/kg) caused induction of IPF in Sprague-Dawley rats. Rats were treated with hesperidin (25, 50, and 100 mg/kg, p.o.) for 28 days, followed by estimation of various parameters in ronchoalveolar lavage fluid (BALF) and lung. Hesperidin (50 and 100 mg/kg) administration significantly meliorated (p < 0.05) alterations induced by BLM in lung index, percent oxygen saturation, serum ALP and LDH levels, BALF differential cell count, and lung function test. Elevated levels of oxido-nitrosative stress, hydroxyproline, and myeloperoxidase levels in BALF and lung were significantly decreased by hesperid in on day 14. Hesperidin significantly inhibited BLM-induced down-regulated lung Nrf2 an d HO-1 as well as up-regulated TNF-α, IL-1β, IL-6, collagen-1, TGF-β, and Smad-3 mRNA expressions. Western blot analysis showed that alteration in lung NF-κ B, Iκ B α , AMPK, and PP2C-α protein expressions were ameliorated by hesperidin on day 28. Furthermore, BLM induced histological and ultrastructural aberrations in the lung which were attenuated by hesperidin treatment. Hesperidin alleviates BLM-induced IPF via inhibition of TGF-β1/Smad3/AMPK and IκBα/NF-κB pathways which in turn ameliorate the modulation of oxido-inflammatory markers (Nrf2 and HO-1) and pro-inflammatory markers (TNF-α, IL-1β, and IL-6) to reduce collagen deposition during pulmonary fibrosis. | en |
| dc.identifier.issn | 1611-2156 | |
| dc.identifier.uri | http://hdl.handle.net/2003/39042 | |
| dc.identifier.uri | http://dx.doi.org/10.17877/DE290R-20961 | |
| dc.language.iso | en | |
| dc.relation.ispartofseries | EXCLI Journal;Vol. 18 2019 | |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
| dc.subject | AMPK | en |
| dc.subject | bleomycin | en |
| dc.subject | hesperidin | en |
| dc.subject | IκBα | en |
| dc.subject | NF-κB | en |
| dc.subject | Nrf2 | en |
| dc.subject | pulmonary fibrosis | en |
| dc.subject | Smad3 | en |
| dc.subject | TGF- β 1 | en |
| dc.subject.ddc | 610 | |
| dc.title | Hesperidin ameliorates bleomycin-induced experimental pulmonary fibrosis via inhibition of TGF-β1/Smad3/AMPK and IκBα/NF-κB pathways | en |
| dc.type | Text | |
| dc.type.publicationtype | article | |
| dcterms.accessRights | open access | |
| eldorado.dnb.zdberstkatid | 2132560-1 | |
| eldorado.secondarypublication | true |