Alcohol-induced oxidative stress is linked to the metabolism of ethanol. Three metabolic pathways of ethanol have been described in the human body so far. They involve the following enzymes: alcohol dehydrogenase, microsomal ethanol oxidation system (MEOS) and catalase. Each of these pathways could produce free radicals which affect the antioxidant system. Ethanol per se, hyperlactacidemia and elevated NADH increase xanthine oxidase activity, which results in the production of superoxide. Lipid peroxidation and superoxide production correlate with the amount of cytochrome P450 2E1. MEOS aggravates the oxidative stress directly as well as indirectly by impairing the defense systems. Hydroxyethyl radicals are probably involved in the alkylation of hepatic proteins. Nitric oxide (NO) is one of the key factors contributing to the vessel wall homeostasis, an important mediator of the vascular tone and neuronal transduction, and has cytotoxic effects. Stable metabolites--nitrites and nitrates--were increased in alcoholics (34.3 +/- 2.6 vs. 22.7 +/- 1.2 micromol/l, p < 0.001). High NO concentration could be discussed for its excitotoxicity and may be linked to cytotoxicity in neurons, glia and myelin. Formation of NO has been linked to an increased preference for and tolerance to alcohol in recent studies. Increased NO biosynthesis also via inducible NO synthase (NOS, chronic stimulation) may contribute to platelet and endothelial dysfunctions. Comparison of chronically ethanol-fed rats and controls demonstrates that exposure to ethanol causes a decrease in NADPH diaphorase activity (neuronal NOS) in neurons and fibers of the cerebellar cortex and superior colliculus (stratum griseum superficiale and intermedium) in rats. These changes in the highly organized structure contribute to the motor disturbances, which are associated with alcohol abuse. Antiphospholipid antibodies (APA) in alcoholic patients seem to reflect membrane lesions, impairment of immunological reactivity, liver disease progression, and they correlate significantly with the disease severity. The low-density lipoprotein (LDL) oxidation is supposed to be one of the most important pathogenic mechanisms of atherogenesis, and antibodies against oxidized LDL (oxLDL) are some kind of epiphenomenon of this process. We studied IgG oxLDL and four APA (anticardiolipin, antiphosphatidylserine, antiphosphatidylethanolamine and antiphosphatidylcholine antibodies). The IgG oxLDL (406.4 +/- 52.5 vs. 499.9 +/- 52.5 mU/ml) was not affected in alcoholic patients, but oxLDL was higher (71.6 +/- 4.1 vs. 44.2 +/- 2.7 micromol/l, p < 0.001). The prevalence of studied APA in alcoholics with mildly affected liver function was higher than in controls, but not significantly. On the contrary, changes of autoantibodies to IgG oxLDL revealed a wide range of IgG oxLDL titers in a healthy population. These parameters do not appear to be very promising for the evaluation of the risk of atherosclerosis. Free radicals increase the oxidative modification of LDL. This is one of the most i...

Biocompatible DNA origami nanostructures (DONs) attract significant interest as potential targeted drug carriers. Their sensitivity to various environmental triggers is beneficial as a drug release or decomposition mechanism, but it also hinders their stability; therefore, they require some extent of cross-linking. Using cisplatin, we demonstrate that a molecule can both act as a therapeutic and cross-linking agent for DONs. In this work, triangular two-dimensional DONs are loaded with ∼1000 cisplatin molecules per nanostructure as confirmed by ICP-MS and STEM-EDS. Time dependence of the loading shows a saturation point and gradual cisplatin release. Above ∼1000 cisplatin molecules loaded per nanostructure, structural distortion occurs as analyzed by AFM and gel electrophoresis. Cross-linking persists even after thermal treatment of cisplatin-loaded DONs above typical DON denaturing temperatures preventing complete separation into DON components (scaffold and staples). Cisplatin-loaded DON cytotoxicity is tested on FaDu cells and compared to that of free cisplatin using MTT assays. Nanomolar quantities of cisplatin-loaded DONs reduce cell viability to 50% after 48–72 h. Considering the low dose required of cisplatin-loaded DONs to exhibit cytotoxic behavior and the known tumor-targeting properties of DONs, this system can be a promising drug carrier for cancer therapy worthy of further exploration.

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