“…Mechanisms of hyperglycemia induced production of oxygen free radicals: Hyperglycemia is known to cause elevation in plasma free radical concentrations (Hammes et al, 1997;Cimato et al, 2008). The production of free radicals is engendered by uncontrolled hyperglycemia, which may occur via several routes (Rolo and Palmeira, 2006;Giacco et al, 2010;Bajaj and Khan, 2012): (1) increased glycolysis (Vaag et al, 1992), (2) intercellular activation of sorbitol (polyol) pathway (Williamson et al, 1993;Di Naso et al, 2011), (3) autoxidation of glucose (Wolff et al, 1991), (4) protein kinase C (PKC) dependent activation of NAD(P)H oxidase (Inoguchi et al, 2003), (5) increased hexosamine pathway flux (Rolo and Palmeira, 2006), 6increased intracellular formation of AGEs (Giacco et al, 2010), 7increased expression of receptor for AGEs and its activating ligands (Giacco et al, 2010) and 8non-enzymatic protein glycation (Ceriello et al, 1992).…”