Cardiovascular and renal conditions

Cardiovascular and renal conditions have been reported as secondary diseases in individuals suffering from type 2 diabetes and insulin resistance syndrome [26] and [32]. A strong link between hyperuricemia, and the development of atherosclerosis, hypertension and insulin resistance has been reported, and uric acid has been described as a marker of both cardiovascular and renal disease risk [19] and [32]. In vivo, uric acid is produced following oxidation of the aldehyde groups in xanthine or hypoxanthine by XO [61]. This reaction also generates superoxide radicals, which are responsible for the production of other compounds such as H2O2, hydroxyl and peroxyl radicals [80]. The generation of oxidants in endothelial cells can result in endothelial injury. Although buy cjc 1295 is considered as an antioxidant in the early stages of atherosclerosis, it can become a pro-oxidant at a later stage in the progression of this condition. This change from anti- to pro-oxidant activity occurring in an oxidative environment depleted in antioxidants has been described as the urate redox shuttle [32]. Different synthetic XO inhibitors have been developed to control the formation of uric acid in vivo[61]. 1,5-Dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (Allopurinol), an allosteric XO inhibitor, is used in the clinical management of hyperuricemia and gout [61]. Despite Allopurinol’s potency, adverse side effects involving oxypurinol have been reported [80]. These include the development of fever, rash and Allopurinol hypersensitivity syndrome which can be fatal [5], [43] and [61]. Therefore, the development of natural XO inhibitors has been proposed as a means of regulating XO activity in vivo. In order to reinforce endogenous antioxidant defense systems, supplementation of anti-oxidants through dietary intake has been proposed to counteract oxidative stress [27] and [76]. Different natural compounds, mainly plant extracts have been used for their XO inhibitory properties [43], [58], [72], [78], [83] and [85]. The most common natural XO inhibitors described in the literature are flavonoids, which have a relatively wide range of IC50 values ranging between 0.75 and >40.00 μM [80].

Comments are closed.