Background: Pulmonary Fibrosis is a chronic lung disease characterized by scar formation and respiratory insufficiency. Metformin is an antidiabetic drug that has recently been shown to prevent lung fibrosis via NADPH oxidase-4 suppression. Flaxseed oil has been shown to be a potent antioxidant that attenuates oxidative damage by inhibition of lipid peroxidation and the proinflammatory cytokine production of IL-6 and TNF-alpha.
Aim: To investigate whether metformin and/or flaxseed oil could protect against bleomycin-induced pulmonary fibrosis and if this protection is mediated by inhibiting NOX-4 signaling pathway and the synthesis and release of inflammatory and oxidative stress markers.
Material and Methods: Fifty adult male rats were randomized into 5 groups/10 rats each.Pulmonary fibrosis was induced by Bleomycin, delivered intratracheally at a concentration of 1.5mg/kg body weight once in group PF, MET, Flax and combined MET& Flax. Both metformin and Flaxseed oil were administered orally for 21 day after induction of PF. Withdrawal of blood samples for chemical and spectral assay of antioxidant markers was done. Histopathology and assessment of inflammatory and fibrotic markers and PCR expression of NOX4 gene were done.
Results: There was a significant reduction in inflammatory cell count, histopathological score of inflammation and fibrosis in the three treatment groups. Also there was marked improvement in inflammatory (IL-6, TNF-a) and fibrotic markers (TGF-B and Col-1) in metformin group rather than flaxseed and combined group.Nox4 gene expression was significantly reduced in metformin treated group rather than other 2 groups