Resveratrol inhibits oxidative damage in lungs of heat-stressed broilers by activating Nrf2 signaling pathway and autophagy

The purpose of this study was to investigate the effects of resveratrol on heat stress-induced lung injury in broilers and the mechanism underlying this process. Sixty two-week-old SPF BWEL broilers were randomly divided into the heat stress group (HS), resveratrol group (heat stress + 400 mg/kg resveratrol), and the control group after one week of feeding, with 20 chickens in each group. Broilers in the control group were reared at 23 ± 2 ℃. Those in the HS and resveratrol group were reared under heat stress (35 ℃ ± 2 ℃) for 8 h/day for seven days. Broilers in the resveratrol group were fed a diet supplemented with 400 mg/kg resveratrol two days before the start of the experiment. The feeding was continued for nine days. The results showed that HS decreased body weight (BW), average daily feed intake (ADFI), average daily gain (ADG), and lung weight. It, however, increased the lung index, induced lung congestion, and promoted infiltration of inflammatory cells to the lung. Resveratrol improved growth performance and inhibited heat stress-induced lung damage. Compared with broilers in the control group, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), Beclin-1, LC3 Ⅰ, and LC3 Ⅱ genes in the lung of heat-stressed broilers was significantly lower. The levels of kelch-like ECH-associated protein 1 (Keap1), NQO1, and HO-1 showed a similar trend with gene expressions. Immunofluorescence indicated that HS inhibited the expression of Nrf2 and LC3B proteins. Finally, the ratio of LC3 Ⅱ/LC3 Ⅰ was also significantly lower in the HS group. Further analyses revealed that resveratrol supplements in feeds enhanced antioxidation in the lung by activating the Nrf2 signaling pathway and autophagy. In conclusion, HS causes oxidative damage and inhibits autophagy in broilers. However, resveratrol protects against lung injury by alleviating oxidative stress and enhancing autophagy.