Agnieszka Augustyniak

Natural and synthetic antioxidants: An updated overview

Abstract The current understanding of the complex role of ROS in the organism and pathological sequelae of oxidative stress points to the necessity of comprehensive studies of antioxidant reactivities and interactions with cellular constituents. Studies of antioxidants performed within the COST B-35 action has concerned the search for new natural antioxidants, synthesis of new antioxidant compounds and evaluation and elucidation of mechanisms of action of both natural and synthetic antioxidants. Representative studies presented in the review concern antioxidant properties of various kinds of tea, the search for new antioxidants of herbal origin, modification of tocopherols and their use in combination with selenium and properties of two promising groups of synthetic antioxidants: derivatives of stobadine and derivatives of 1,4-dihydropyridine.

l-Carnitine in the lipid and protein protection against ethanol-induced oxidative stress.

Chronic ethanol intoxication induces oxidative stress participating in the development of many diseases. Nutrition and the interaction of food nutrients with ethanol metabolism may modulate alcohol toxicity. One such compound is l-carnitine (l-3-hydroxy-4-N,N,N-trimethylaminobutyrate), which also reveals antioxidant abilities. The present study has been designed to investigate the effect of l-carnitine as an antioxidant on the serum and liver of rats chronically intoxicated with ethanol. Rats received l-carnitine solution (1.5g/1L) for 5 weeks and/or were treated intragastrically with ethanol for 4 weeks. In the serum and liver, the level of nonenzymatic antioxidants and lipid and protein oxidation markers were determined. It was shown that alcohol caused the increase in the level of lipid peroxidation products-conjugated dienes (by about 70% and 60% in the liver and blood serum, respectively), malondialdehyde (MDA) (by about 60% and 30% in the liver and blood serum, respectively), 4-hydroxynonenal (4-HNE) (by about 35% and 25% in the liver and blood serum, respectively), and changes in the level of protein oxidative markers-increase in dityrosine and decrease in tryptophan (by about 40%) in the serum and liver of rats. Moreover, the decrease in vitamin E level (by about 30%) and the level of glutathione (GSH) (by about 20% in the liver and blood serum) was also observed. Administration of l-carnitine to rats intoxicated with ethanol significantly protects lipids and proteins against oxidative modifications in the serum and liver. The level of conjugated dienes, MDA, and 4-HNE was decreased by about 30%, 30%, and 20% in the liver, respectively, and by about 20%, 10%, and 10% in the blood serum in comparison to the ethanol group. Moreover, the level of tryptophan was increased and dityrosine decreased by about 10% and 20% in the liver, respectively, and by about 30% and 10% in the blood serum in comparison to the ethanol group. l-carnitine partially protects nonenzymatic antioxidants against oxidative stress. The level of vitamin E was increased by about 20% and the level of GSH was increased by about 25% in the liver and blood serum in comparison to the ethanol group. It is possible that beneficial effect of l-carnitine is connected with its abilities to scavenge free radicals and to chelate metal ions.

The Influence of L-Carnitine on Oxidative Modification of LDL In Vitro

ABSTRACT Owing to their structure and function, low-density lipoproteins (LDLs) are particularly susceptible to the oxidative modifications. To prevent against oxidative modification of LDL, L-carnitine, with endogenous small water-soluble quaternary amine possessing antioxidative properties, was used. The aim of this paper was to prove the in vitro influence of L-carnitine on the degree of oxidative modification of the lipid part (estimated by conjugated dienes, lipid hydroperoxides, and malondialdehyde levels) and the protein part (estimated by dityrosine and tryptophan levels) of LDL native and oxidized by cooper ions. The level of lipophylic LDL antioxidant—α-tocopherol was also measured. Oxidation of LDL by Cu2+ enhanced lipid peroxidation. That was manifested by a statistically significant increase in the content of malondialdehyde (threefold), conjugated dienes (up to about 30%), and lipid hydroperoxides (up to about 50%). Cu2+ ions were also the cause of oxidative modifications of the protein part of LDLs. It was manifested by a significant increase in dityrosine (by about 50%), whereas the level of tryptophan was significantly decreased threefold in relation to native LDL. Incubation of LDL with Cu2+ ions also caused a significant sixfold decrease of α-tocopherol content in oxidized LDL. However, L-carnitine caused a decrease in the level of conjugated dienes, lipid hydroperoxide, malondialdehyde, and dityrosine by about 20% to 30%, and a significant increase (by about 50%) in the content of tryptophan in comparison with oxidative LDL and in a smaller degree significant changes with native LDL. Additionally, L-carnitine caused a significant twofold increase in α-tocopherol content in oxidized LDL. The above results indicate that L-carnitine protects the lipid as well as protein part of LDL particles against oxidative modifications, and this natural antioxidant might be used to prevent against diseases of oxidative origin.

Black-Currant Protection Against Oxidative Stress Formation

The aim of this study was to investigate the influence of black-currant juice on chronic ethanol-induced oxidative stress and its consequences in liver, brain, and serum of rats. Data demonstrated that administration of black-currant juice to rats improved antioxidant abilities in the examined tissues as evidenced by measurement of activities of Cu,Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GSSG-R), as well as levels of glutathione (GSH) and vitamins C, E, and A. Ethanol intoxication produced a decrease in the activities and levels of the antioxidants just listed, and the decrease was accompanied by a reduction in levels of arachidonic acid (AA) and docosahexaenoic acid (DHA). Further results showed enhanced lipid peroxidation as determined by malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and neuroprostanes and elevated protein levels such as carbonyl groups and dityrosine. Ethanol intoxication altered liver metabolism as evidenced by a decrease in peroxisome proliferator-activated-receptor (PPARα), AMP-dependent protein kinase (AMPK), and nuclear factor kappa B cells (NFκB) and by an increase in tumor necrosis factor (TNF-α) expression. Administration of black-currant juice to ethanol-intoxicated rats exerted an antioxidant response by restoring to normal quantities the antioxidant levels and enzyme activities and prevented lipid and protein oxidative effects. The activities of alanine transaminase and aspartate transaminase, biomarkers of liver damage, returned to normal after black-currant treatment of ethanol-administered animals. In addition, the expression of PPARα, AMPK, TNF-α, and NFκB confirmed the protective effect of the juice. Data thus indicate the extensive antioxidant metabolic effects of black-currant juice that may be beneficial for humans.

Chapter 25 – Green and Black Tea in Brain Protection

Several lines of evidence suggest that enhanced reactive oxygen species (ROS) generation and a decrease in antioxidative abilities are the reasons for oxidative stress (OS) followed by subsequent inflammation, which plays a pivotal role in neurodegenerative disorders such as Parkinsons disease (PD) and Alzheimers disease (AD). Thus, antioxidative defense is critically important in nervous tissue protection. Several potent antioxidants, especially those belonging to natural products, have been investigated. One such potentially health promoting beverage is tea, especially green tea whose components, mainly catechins and catechin derivates, have proven antioxidant properties. The protective effects of green tea extract on the central nervous system tissue expression in decreased levels of lipid peroxidation products have been shown. A large study investigating PD found a moderate risk reduction in tea consumers compared to non-tea drinkers. However, the investigations of the past few years show that black tea components also possess antioxidative properties, which have been proven in vitro as well as in vivo experiments. The specific mechanisms by which tea polyphenols exert their neuroprotective action are not clearly defined. However, recent evidence indicates that besides their antioxidant and iron chelating properties, polyphenols have a profound effect on cell survival/death genes and signal transduction. The revelation of novel molecular targets possibly implicated in their neuroprotective action include calcium homeostasis, the extracellular mitogen-activated protein kinases (MAPK), protein kinase C (PKC), antioxidant enzymes, antioxidant regulatory element (ARE) survival genes, and processing of the amyloid precursor protein (APP) pathway.

Age-dependent changes in the proteolytic-antiproteolytic balance after alcohol and black tea consumption.

Aging is accompanied by changes in the redox balance that is additionally modified by alcohol. Ethanol metabolism is connected with generation of free radicals which can damage cell components especially when antioxidant mechanisms are not able to neutralize them. In connection with the necessity of prevention against oxidative consequences, natural antioxidants are looked for. A natural and commonly used component of the diets with antioxidant properties are teas, especially the black tea. This study provides evidence of the role of black tea in the protection of rat plasma proteins and lipids against oxidative stress caused by aging and ethanol intoxication. For 5 weeks, the rats (2-, 12-, and 24-months old) used for the experiment received a black tea beverage (3 g/l) without or with alcohol (given for 4 weeks). The decrease in antioxidant abilities determined as total antioxidant status during aging and ethanol intoxication resulted in enhanced lipid and protein oxidation (determined as malondialdehyde, carbonyl groups, dityrosine, tryptophan and sulfhydryl groups level). In consequence the decrease in anti-proteases (alpha-1-antitrypsin, alpha-2-macroglobulin) activity and the increase in proteases (elastase and cathepsin G) activity were observed. Black tea protected the plasma antioxidants and prevented oxidative modifications of lipid and protein observed during aging as well as ethanol intoxication. The results indicate that a shift into plasma proteolytic activity results from a decrease in antioxidant abilities, so the use of black tea appears to be beneficial in reducing oxidative stress caused by ethanol and/or aging.

Tea and Liver Antioxidant Capabilities in Ethanol Toxicity

It is known that ethanol intoxication leads to oxidative stress formation, because its metabolism is accompanied by free radical generation. This can damage cell components, especially when antioxidant mechanisms cannot neutralize the radicals. Among natural antioxidants, the most popular beverage consumed worldwide is tea. Tea polyphenols possess proven antioxidant properties that are shown by their ability to inhibit free radical generation, scavenge free radicals, chelate transition metal ions and protect the antioxidant system. It has been shown that green tea prevents changes in antioxidant enzyme activity (superoxide dismutase, glutathione peroxidase and catalase), while black tea protects glutathione peroxidase and catalase in the liver of rats intoxicated with ethanol. Moreover, both kinds of tea protect the liver’s non-enzymatic antioxidants including GSH and vitamins C and E, against alcohol action. In consequence, tea prevents ethanol-induced oxidative modifications of cellular components of the liver, such as lipids. Tea is consumed throughout the world, and is believed to be not only a popular beverage but also an antioxidative agent available in everyday life.