New conjugates of β-cyclodextrin with manganese(iii) salophen and porphyrin complexes as antioxidant systems

Oxidative stress has become widely viewed as an underlying condition in a number of diseases, such as ischemia-reperfusion disorders, central nervous system disorders, cardiovascular conditions, cancer, and diabetes. Thus, natural and synthetic antioxidants have been actively sought. Superoxide dismutase is a first line of defense against oxidative stress under physiological and pathological conditions. Therefore, the development of therapeutics aimed at mimicking superoxide dismutase was a natural maneuver. Metalloporphyrins, as well as Mn cyclic polyamines, Mn salen derivatives and nitroxides were all originally developed as SOD mimics. The same thermodynamic and electrostatic properties that make them potent SOD mimics may allow them to reduce other reactive species such as peroxynitrite, peroxynitrite-derived CO(3)(*-), peroxyl radical, and less efficiently H(2)O(2). By doing so SOD mimics can decrease both primary and secondary oxidative events, the latter arising from the inhibition of cellular transcriptional activity. To better judge the therapeutic potential and the advantage of one over the other type of compound, comparative studies of different classes of drugs in the same cellular and/or animal models are needed. We here provide a comprehensive overview of the chemical properties and some in vivo effects observed with various classes of compounds with a special emphasis on porphyrin-based compounds.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Western world. Its incidence has been increasing lately in developing countries. Several lines of evidence support a role for oxidative stress in atherogenesis. Growing evidence indicates that chronic and acute overproduction of reactive oxygen species (ROS) under pathophysiologic conditions is integral in the development of cardiovascular diseases (CVD). ROS mediate various signaling pathways that underlie vascular inflammation in atherogenesis from the initiation of fatty streak development through lesion progression to ultimate plaque rupture. Various animal models of oxidative stress support the notion that ROS have a causal role in atherosclerosis and other cardiovascular diseases. Human investigations also support the oxidative stress hypothesis of atherosclerosis. Oxidative stress is the unifying mechanism for many CVD risk factors, which additionally supports its central role in CVD. A main source of ROS in vascular cells is the reduced nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase system. This is a membrane-associated enzyme, composed of five subunits, catalyzing the one-electron reduction of oxygen, using NADH or NADPH as the electron donor. This system is an important target for genetic investigations. Identification of groups of patients with genetically prone or resistant of oxidative stress is therefore an obvious target of investigation. A better understanding of the complexity of cellular redox reactions, development of a new class of antioxidants targeted to specific subcellular sites, and the phenotype-genotype linkage analysis for oxidative stress will likely be avenues for future research with regards to the broader use of pharmacological therapies in the treatment and prevention of CVD.

Oxidative damage is a major feature in the pathophysiology of Alzheimer's disease (AD). In this review, we discuss free radical-mediated damage to the biochemical components involved in the pathology and clinical symptoms of AD. We explain how amyloid beta-protein (Abeta), microtubule-associated protein tau, presenilins, apolipoprotein E, mitochondria and proteases play a role in increasing oxidative stress in AD. Abeta not only can induce oxidative stress, but its generation is also increased as a result of oxidative stress. Finally, a hypothetical model linking oxidative stress with beta-amyloid and neurofibrillary tangle pathology in AD is proposed.