title: Resveratrol alleviates endotoxemia-associated adrenal insufficiency by suppressing oxidative/nitrative stress.
abstract: We have recently demonstrated that endotoxin causes oxidative stress and overproduction of nitric oxide in adrenal glands, thereby leading to adrenocortical insufficiency. The aim of this study is to investigate the effects of resveratrol, a natural plant polyphenol with anti-oxidant and anti-nitrative properties, on endotoxemia-associated adrenocortical insufficiency. Resveratrol was administered immediately before injection of lipopolysaccharide (LPS). Twenty four hours later, the adrenocorticotropic hormone (ACTH) stimulation tests was been performed to measure the plasma corticosterone level and the adrenal gland tissues were collected for histopathologic examination, and determination of malondialdehyde (MDA), total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity, inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) and peroxynitrite production. Treatment with resveratrol significantly inhibited endotoxemia-induced iNOS expression, NO production, and peroxynitrite formation and also attenuated LPS-induced oxidative stress in the adrenal gland, as evidenced by the decrease of pro-oxidant biomarker (MDA), and the increases of anti-oxidant biomarkers (T-AOC, CAT and SOD activity). H&E staining demonstrated that administration of LPS resulted in increased into the adrenal gland. H&E-stained sections of adrenal glands demonstrated signs of leukocyte infiltration and hemorrhage during endotoxemia, which were significantly improved by resveratrol treatment. In addition, resveratrol reversed the LPS-induced downregulation of ACTH receptor and silent information regulator 1 (SIRT1) in adrenal gland, as well as adrenocortical hyporesponsiveness to ACTH. Resveratrol exerts protective effects against endotoxemia-associated adrenocortical insufficiency by suppressing oxidative/nitrative stress. These findings support the potential for resveratrol as a possible pharmacological agent to improve adrenocortical insufficiency resulting from oxidative/nitrative damage.
authors.affiliation: Department of Physiology and The Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai 200433, China.
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Duan
authors.forename: Chang-Nan
authors.initials: CN
authors.lastname: Wang
authors.forename: Yu-Jian
authors.initials: YJ
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.forename: Xiao-Lu
authors.initials: XL
authors.lastname: Tang
authors.forename: Xin
authors.initials: X
authors.lastname: Ni
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhu
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000309:Adrenal Insufficiency / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects*; D019446:Endotoxemia / Q000139:chemically induced / Q000150:complications* / Q000517:prevention & control; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013267:Stilbenes; D009569:Nitric Oxide; D008315:Malondialdehyde; D000077185:Resveratrol