Previous studies examining the involvement of oxidative stress in the substantia nigra in Parkinson's disease have measured terminal products of lipid peroxidation or the function of antioxidant defense systems. We report a more specific early marker of lipid peroxidation, lipid hydroperoxides, in a high-performance liquid chromatography (HPLC) and electron spin resonance (ESR) investigation. HPLC-chemiluminescent detection revealed two classes of lipid hydroperoxides in brain tissue extracts--free fatty acid hydroperoxides and cholesterol lipid hydroperoxides. Only cholesterol lipid hydroperoxides were consistently detected in all tissue extracts. Cholesterol lipid hydroperoxides had a 10-fold increase in the Parkinson's disease substantia nigra compared to control subjects. ESR detection of radical degradation products, including those of lipid hydroperoxides, in nigral homogenates incubated with the spin trap N-t-butyl-alpha-phenyl nitrone (PBN) showed a marked variation in ESR signal between tissues. Despite the increased levels of lipid hydroperoxides in parkinsonian substantia nigra, there was no overall difference in ESR signal intensity between nigral tissues from controls and from patients with Parkinson's disease. The increased levels of an early component of the peroxidation chain in substantia nigra in Parkinson's disease support the hypothesis of a continuous toxic process involving oxygen radical activity. However, using previously frozen tissue, ESR evidence for increased radical formation could not be demonstrated.
In this prospective, randomized, double-blind, placebo-controUed study, the clinical, biochemical, and hemodynamic effects of xanthine oxidase inhibition in patients undergoing coronary artery bypass grafting were assessed. AUopurinol pretreatment significantly reduced the use of inotropic support after the operation (5 of 25 patients versus 13 of 25 patients, p < 0.01) and increased the rate of peripheral warming (11.4 ± 0.85 hours versus 14.4 ± 1 hours, p < 0.02). Twenty patients (9 in the aUopurinol group and 11 in the placebo group) underwent invasive hemodynamic monitoring and intraoperative coronary sinus cannulation. The cardiac indexes of both groups were similar before the operation and for the first postoperative hour; thereafter, the cardiac index increased significantly in only the active treatment group (F = 3.33 and df= 5,90, p < 0.004). Products of lipid peroxidation (thiobarbituric acid reactive substances) increased significantly in only the placebo group, with increases being evident both in the systemic circulation (9.5 ± 3.2 nmol/gm albumin, p < 0.007, and 24 ± 5 nmoljgm albumin, p < 0.001, at 30 seconds and 2 minutes of reperfusion, respectively) and the coronary sinus (19.4 ± 5.8 nmol/gm albumin, p < 0.004, and 28 ± 4 nmol/gm albumin, p < 0.001, at 2 and 5 minutes of reperfusion, respectively. No significant difference was evident between the groups with respect to cardiac enzyme or vitamin E release. It is proposed that xanthine oxidase inhibition exerts its beneficial effects by reducing the level of free radical activity associated with reperfusion during coronary artery bypass grafting.
In the presence of physiological concentrations of iron(III) salts, superoxide radical and hydrogen peroxide can interact to form the highly‐damaging hydroxyl radical. No specific added ‘chelator’ of iron salts is necessary for this reaction to occur.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.