Chronic stress-induced oxidative damage and hyperlipidemia are accompanied by atherosclerotic development in rats

Abstract

Although stress-induced hyperlipidemia and increased oxidative stress have been reported and implicated in etiology of atherosclerosis, experimental evidence for stress-induced atherosclerotic development concomitant with these alterations is lacking. In this study, exposure of adult male albino Wistar rats (Rattus norvegicus) to restraint for 1 h and after a gap of 4 h to forced swimming for 15 min every day for 2, 4, or 24 weeks resulted in a duration of exposure-dependent hyperlipidemia as shown by significant increases in concentrations of blood cholesterol, low-density lipoproteins, and triglycerides and decrease in high-density lipoprotein concomitant with increased oxidative stress as indicated by decrease in hepatic antioxidant enzyme activities and increase in lipid peroxidation in the liver, kidney, and heart. These alterations were accompanied by development of fibrous layer, formation of foam cells, reduction in elastic fibers, and accumulation of Oil-Red-O-positive lipid droplets in the intima of thoracic aorta following 24 weeks of stress exposure, but not after 4 weeks. The study demonstrates for the first time that (i) chronic stress-induced hyperlipidemia and oxidative damage are coupled with atherosclerotic development in rats fed with normal diet and (ii) chronic stress effects prevail even after the cessation of stress exposure as indicated by high concentration of blood cholesterol and reduced hepatic superoxide dismutase activity 20 weeks after 2 or 4 weeks of stress. This study exemplifies long-term allostatic regulation leading to a pathological state, with long-term hyperlipidemia and oxidative damage from chronic stress resulting in atherosclerosis.

Chronic psychological stress and high-fat high-fructose diet disrupt metabolic and inflammatory gene networks in the brain, liver, and gut and promote behavioral deficits in mice

“…In addition, Feng et al demonstrated that forced swim stress elevates cholesterol content in the brain (Feng et al, 2015). Another study using 1 h of restraint in association with forced swim found significant increases in blood cholesterol with stress in rats (Devaki et al, 2013). Herein we show that 15 min a day of psychological stress for 14 days is sufficient to affect circulating cholesterol levels in an obesogenic environment.…”

Sociodemographic, behavioral and genetic determinants of allostatic load in a Swiss population-based study

“…adrenaline, noradrenaline) as they were not available in SKIPOGH. Moreover, we decided to include an oxidative stress axis as chronic oxidative stress has also been linked to generalized physiological dysregulation (Devaki et al, 2013;Nicod et al, 2014). Further, we separated the lipids from the metabolism axes contrary to previous studies.…”

Chronic stress impacts the cardiovascular system: animal models and clinical outcomes

“…However, some have questioned the relevance of this behavior (floating), since it may be an acquired lifesaving behavior for preserving energy (292,362). Atherosclerosis-promoting effects of forced swimming haves been shown in a stress protocol consisting of restrain and forced swimming in rats fed a normal diet (73). This chronic stress model enhanced different aspects of atherosclerosis including increases in cholesterol and triglycerides blood levels, decreased HDL, increased oxidative stress, reduction of vascular elastic fibers, and boosted foam cell formation.…”