Dietary docosahexaenoic acid supplementation prevents the formation of cholesterol oxidation products in arteries from orchidectomized rats

Abstract

Testosterone deficiency has been correlated with increased cardiovascular diseases, which in turn has been associated with increased oxidative stress. Several studies have considered cholesterol oxidation products (COPs) as oxidative stress biomarkers, since some of them play pro-oxidant and pro-inflammatory roles. We have previously described the cardioprotective effects of a dosahexaenoic acid (DHA) supplemented diet on the aortic and mesenteric artery function of orchidectomized rats. The aim of this study was to investigate whether impaired gonadal function alters the formation of COPs, as well as the potential preventive role of a DHA-supplemented diet on that effect. For this purpose, aortic and mesenteric artery segments obtained from control and orchidectomized rats, fed with a standard or supplemented with DHA, were used. The content of the following COPs: 7α-hydroxycholesterol, 7β-hydroxycholesterol, 7-ketocholesterol, 5,6α-epoxycholesterol, 5,6β-epoxycholesterol, cholestanetriol and 25-hydroxycholesterol, were analyzed by gas chromatography. The results showed that orchidectomy increased the formation of COPs in arteries from orchidectomized rats, which may participate in the orchidectomy-induced structural and functional vascular alterations already reported. The fact that the DHA-supplemented diet prevented the orchidectomy-induced COPs increase confirms the cardiovascular protective actions of DHA, which could be of special relevance in mesenteric arterial bed, since it importantly controls the systemic vascular resistance.

7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity

“…There are now several lines of evidence that 7KC and 7β-OHC have major impacts on the metabolism of cancer cells [250], supporting the concept that chemotherapies targeting metabolism offer promising perspectives for cancer treatment. The rat model has been used to study the metabolism of 7KC [26,50,251], to identify molecules capable of preventing cardiovascular injuries [252] and to determine the impact of some nutrients and aliments on the biogenesis of oxysterols formed by auto-oxidation including 7KC and 7β-OHC [253][254][255]. In addition, using 7KC-containing implants inserted into the anterior chamber of the rat eye, it has been demonstrated that the cytokinic inflammation induced by 7KC mostly occurs through the TLR4 receptor [169].…”