Kandhare, Amit D.
Kandhare, Anwesha A.
Bodhankar, Subhash L.
|Title:||Hesperidin ameliorates bleomycin-induced experimental pulmonary fibrosis via inhibition of TGF-β1/Smad3/AMPK and IκBα/NF-κB pathways|
|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.|
TGF- β 1
|Appears in Collections:||Original Articles|
Files in This Item:
|Bodhankar_29082019_proof.pdf||DNB||3.43 MB||Adobe PDF||View/Open|
This item is protected by original copyright
This item is licensed under a Creative Commons License