Overproduction of nitric oxide by endothelial cells and macrophages contributes to mitochondrial oxidative stress in adrenocortical cells and adrenal insufficiency during endotoxemia

Resveratrol alleviates endotoxemia-associated adrenal insufficiency by suppressing oxidative/nitrative stress

“…We have previously shown that the increases in adrenal iNOS expression and NO production contribute to LPS-induced adrenal insufficiency [15]. In the present study, it was found that treatment of resveratrol significantly attenuated the elevated iNOS expression in adrenal glands of endotoxemic mice in a dosedependent manner (Fig.…”

“…Total NO production by adrenal glands was determined by measuring the concentration of nitrite, a stable metabolite of NO in vitro, with a modified Griess (sigma-Aldrich) reaction method [15]. The absorbance was measured at 550 nm using a Bio-Rad (Hercules, CA) microplate reader and nitrite concentration was assessed by reference to the sodium nitrite standard curve.…”

“…The adrenal steroidogenic cells are particularly vulnerable to oxidative stress due to their unique ultramicrostructure and function [7]. In the adrenocortical cells, excessive amounts of molecular oxygen are used not only for aerobic energy production (ATP synthesis) in mitochondria but also for steroid biosynthesis, which generates reactive oxygen species (ROS) such as oxygen-centered free radicals and peroxides as by-products of oxidative metabolism [7,14,15]. Moreover, since the adrenocortical cells contain a high content of unsaturated membrane lipids, lipid peroxidationmediated oxidative damage of cellular membranes can adversely affect cholesterol processing and steroidogenesis [7,14,15].…”

“…In the adrenocortical cells, excessive amounts of molecular oxygen are used not only for aerobic energy production (ATP synthesis) in mitochondria but also for steroid biosynthesis, which generates reactive oxygen species (ROS) such as oxygen-centered free radicals and peroxides as by-products of oxidative metabolism [7,14,15]. Moreover, since the adrenocortical cells contain a high content of unsaturated membrane lipids, lipid peroxidationmediated oxidative damage of cellular membranes can adversely affect cholesterol processing and steroidogenesis [7,14,15]. Our previous studies have shown that LPS treatment results in mitochondrial oxidative damage in the adrenal gland, which probably leads to the decline of corticosterone responsiveness to exogenous ACTH [14,15].…”

“…Moreover, since the adrenocortical cells contain a high content of unsaturated membrane lipids, lipid peroxidationmediated oxidative damage of cellular membranes can adversely affect cholesterol processing and steroidogenesis [7,14,15]. Our previous studies have shown that LPS treatment results in mitochondrial oxidative damage in the adrenal gland, which probably leads to the decline of corticosterone responsiveness to exogenous ACTH [14,15]. In addition, oxidative stress has also been implicated in adrenocortical dysfunction associated with aging, metal toxicity, and side-effects of anesthetic agents such as etomidate [2,22,23].…”