Oxidative Stress and Molecular Reactions in Arteriogenic Erectile Dysfunction

Abstract

Vascular disorders are the leading causes of organic erectile dysfunction (ED). Most cases of arteriogenic ED are associated with vascular risk factors such as hypercholesterolemia, atherosclerosis, diabetes mellitus, hypertension, and smoking. These conditions impair vascular structure directly or indirectly by facilitating oxidative damage due to accumulation of reactive oxygen and nitrogen species such as superoxide (O 2 − ), hydrogen peroxide (H 2 O 2 ), hydroxyl radicals and peroxynitrite (O=NOO − ). Clinical studies have shown that the degree of arteriogenic ED cannot be predicted exclusively by the arterial integrity, suggesting that it involves local changes within penile smooth muscle cells, endothelium, nerves, and microvasculature. It is thought that arterial occlusion and subsequent lack of erectile tissue perfusion, nutrient deficiency, hypoxia, and accumulation of waste products constitute an environment hospitable to free radical formation and detrimental to nitric oxide (NO) bioavailability. Studies of animal and cell culture models have revealed that exposure to ischemia and hypoxia triggers a cascade of cellular and molecular changes in the erectile tissue with devastating impact on its structure and function. These alterations involve cytotoxic radicals, nitric oxide synthase (NOS), eicosanoids, neurotoxic elements, and growth factors and lead to impairment of NO/cGMP pathway, smooth muscle dysfunction, microvascular damage, and neurodegeneration. Ultimately, these events lead to erectile tissue fibrosis and the failure of penile veno-occlusive mechanism. These local changes in the hypoxic erectile tissue may explain the failure of revascularization surgery to completely cure arteriogenic ED and imply the need for newer therapeutic strategies to remove cytotoxic and neurotoxic elements from the chronically ischemic penis.

Seed extracts from Myristica fragrans (Nutmeg) and Moringa oleifera (Drumstick tree) inhibits enzymes relevant to erectile dysfunction and metal-induced oxidative damage in rats' penile tissues

“…Overproduction of free radicals may contribute to lipid peroxidation, penile tissue fibrosis, microvascular damage, and disruption of penile erection mechanisms which may lead to vasculogenic ED (Azadzoi & Siroky, ; Prathapan, Vineetha, Abhilash, & Raghu, ). The inhibition of MDA production by the extracts was assessed in rats' penile homogenates using Fe 2+ as pro‐oxidant.…”

Effects of water extractable phytochemicals of mahogany (Swietenia macrophylla) and axlewood (Anogeissus leiocarpus) stem bark on some enzymes implicated in erectile dysfunction and type-2 diabetes

“…Radical, especially reactive oxygen species are capable of reacting with NO causing endothelial cell damage (Moreland, 2013). Thus, prevention of radical generation and reducing power of phenolic compounds through redox property are highly desirable in ED management (Amic, Davidovic-Amic, Beslo, & Trinajstic, 2003;Azadzoi & Mike, 2009). Polyphenols have gained the interest in food and drug manufacturers due to their promising health benefits (Scalbert, Manach, Morand, & Remesy, 2005).…”

Erectogenic, Antihypertensive, Antidiabetic, Anti-Oxidative Properties and Phenolic Compositions of Almond Fruit (Terminalia catappaL.) Parts (Hull and Drupe) -in vitro

“…5, 6 and 7). Thus, prevention of radical species is highly desirable in the management of ED (Azadzoi and Mike 2009). 5 and 6).…”

“…Peroxynitrite (O 5 NOO 2 ) formation from the combination of singlet oxygen or superoxide radical in an elevated NO environment may attack the endothelial cells causing neuronal damage, vascular rigidity, decreased bioavailability of endothelial and neuronal NO (Moreland 2013). Thus, prevention of radical species is highly desirable in the management of ED (Azadzoi and Mike 2009). The reducing powers of the phenolic compounds are also based on their redox property (Amic et al 2003).…”