Resveratrol potentiates the effect of dexamethasone in rat model of acute lung inflammation

• Resveratrol reinstated effectiveness of dexamethasone in lung inflammation induced by cigarette smoke & lipopolysaccharide.
• Resveratrol + dexamethasone combination reduced leukocyte count, MMP-9, TNF-α, IL-8 in BALF, MPO & lipid peroxidation in lung.
• Combination therapy may serve as a potential approach for treating lung inflammatory conditions like COPD.

Cigarette smoking is considered to be the main etiological factor in Chronic Obstructive Pulmonary Disease (COPD). In this study, we explored the potential of resveratrol, to reinstate the effectiveness of dexamethasone when administered as an adjunct in acute lung inflammation induced by cigarette smoke (CS) and lipopolysaccharide (LPS). CS and LPS instillation produced acute inflammatory response exhibited by increased leukocyte count, particularly neutrophils, total protein, MMP-9 activity, cytokines like TNF-α, IL-8 in bronchoalveolar lavage fluid (BALF) as well as elevated myeloperoxidase activity, and lipid peroxidation in lung. These alterations were not abated by dexamethasone (2.5 mg/kg & 10 mg/kg) and resveratrol (50 mg/kg) alone. Combination of resveratrol (50 mg/kg) and dexamethasone (2.5 mg/kg) significantly reduced all inflammatory parameters. The protective effect of the combination was abolished when co-administered with sirtinol, a SIRT1 inhibitor. The results indicate that the combination therapy may serve as a potential approach for treating lung inflammatory conditions like COPD.