Protective effect of resveratrol against endotoxemia-induced lung injury involves the reduction of oxidative/nitrative stress.
BACKGROUND
Resveratrol, a natural plant polyphenol, has received increasing attention because its varied bioactivities, including the inhibition of tumorigenesis, lipid modification and calorie-restriction. We aimed to investigate the effect of resveratrol on oxidative/nitrative stress in endotoxemia-associated acute lung injury.


METHODS
Mice were injected with lipopolysaccharide (LPS, 5 mg/kg, ip). Resveratrol at a dose of 0.3 mg/kg was administered alone or immediately before injection of LPS. Twenty four hours later, lung tissues were collected for histopathologic examination, and determination of malondialdehyde (MDA), H2O2, reduced/oxidized glutathione (GSH/GSSG) ratio, total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity, inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) and peroxynitrite production.


RESULTS
Resveratrol treatment improves histopathological changes in the lung during endotoxemia. Increased oxidative stress in endotoxemic lung was reversed by resveratrol treatment, as evidenced by the decreases of pro-oxidant biomarker (MDA and H2O2), and the increases of anti-oxidant biomarkers (GSH/GSSG ratio, T-AOC, CAT and SOD activity). Treatment with resveratrol inhibited endotoxemia-induced iNOS expression and NO production. Moreover, peroxynitrite formation in endotoxemic lung was significantly attenuated after resveratrol treatment.


CONCLUSIONS
Resveratrol exerts protective effects against acute endotoxemia-associated lung injury. These beneficial effects may be due to both the anti-oxidant and anti-nitrative properties of resveratrol. These findings support the potential for resveratrol as a possible pharmacological agent to reduce acute lung injury resulting from oxidative/nitrative damage.
Department of Physiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China; Department of Respiration, Kongjiang Hospital, Shanghai 200093, China.
Hong-Xia
HX
Zhang
The Eight-year Program on Clinical Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Guo-Li
GL
Duan
Department of Physiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
Chang-Nan
CN
Wang
Department of Physiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
Yun-Qian
YQ
Zhang
Department of Physiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. Electronic address: xiaoyanzhu@smmu.edu.cn.
Xiao-Yan
XY
Zhu
Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. Electronic address: liuyujianz@yahoo.com.cn.
Yu-Jian
YJ
Liu
D055371:Acute Lung Injury / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000150:complications / Q000188:drug therapy; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects*; D030421:Peroxynitrous Acid / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D008070:Lipopolysaccharides; D013267:Stilbenes; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D000077185:Resveratrol
Endotoxemia; Lung; Nitrative stress; Oxidative stress; Resveratrol