Cobalt intoxication can occur after its release from metal-based prostheses, which is generally clinically severe. Therefore, there is a need for the development of a cobalt chelator since there are currently no approved drugs for cobalt intoxication. As flavonoids are known for their metal chelating properties and safety, the screening of cobalt chelating properties was performed in a total of 23 flavonoids by our recently developed new spectrophotometric assay. Further assessment of positive or negative consequences of cobalt chelation was performed both in vitro and ex vivo. Six and thirteen flavonoids significantly chelated cobalt ions at pH 7.5 and 6.8, respectively. Baicalein demonstrated a significant activity even at pH 5.5; however, none of the flavonoids showed chelation at pH 4.5. In general, baicalein and 3-hydroxyflavone were the most active. They also mildly decreased the cobalt-triggered Fenton reaction, but baicalein toxicity toward red blood cells was strongly increased by the addition of cobalt. Quercetin, tested as an example of flavonoid unable to chelate cobalt ions significantly, stimulated both the cobalt-based Fenton reaction and the lysis of erythrocytes in the presence of cobalt. Therefore, 3-hydroxyflavone can serve as a potential template for the development of novel cobalt chelators.

• Publikační typ
• časopisecké články MeSH

A physiological level of oxygen/nitrogen free radicals and non-radical reactive species (collectively known as ROS/RNS) is termed oxidative eustress or "good stress" and is characterized by low to mild levels of oxidants involved in the regulation of various biochemical transformations such as carboxylation, hydroxylation, peroxidation, or modulation of signal transduction pathways such as Nuclear factor-κB (NF-κB), Mitogen-activated protein kinase (MAPK) cascade, phosphoinositide-3-kinase, nuclear factor erythroid 2-related factor 2 (Nrf2) and other processes. Increased levels of ROS/RNS, generated from both endogenous (mitochondria, NADPH oxidases) and/or exogenous sources (radiation, certain drugs, foods, cigarette smoking, pollution) result in a harmful condition termed oxidative stress ("bad stress"). Although it is widely accepted, that many chronic diseases are multifactorial in origin, they share oxidative stress as a common denominator. Here we review the importance of oxidative stress and the mechanisms through which oxidative stress contributes to the pathological states of an organism. Attention is focused on the chemistry of ROS and RNS (e.g. superoxide radical, hydrogen peroxide, hydroxyl radicals, peroxyl radicals, nitric oxide, peroxynitrite), and their role in oxidative damage of DNA, proteins, and membrane lipids. Quantitative and qualitative assessment of oxidative stress biomarkers is also discussed. Oxidative stress contributes to the pathology of cancer, cardiovascular diseases, diabetes, neurological disorders (Alzheimer's and Parkinson's diseases, Down syndrome), psychiatric diseases (depression, schizophrenia, bipolar disorder), renal disease, lung disease (chronic pulmonary obstruction, lung cancer), and aging. The concerted action of antioxidants to ameliorate the harmful effect of oxidative stress is achieved by antioxidant enzymes (Superoxide dismutases-SODs, catalase, glutathione peroxidase-GPx), and small molecular weight antioxidants (vitamins C and E, flavonoids, carotenoids, melatonin, ergothioneine, and others). Perhaps one of the most effective low molecular weight antioxidants is vitamin E, the first line of defense against the peroxidation of lipids. A promising approach appears to be the use of certain antioxidants (e.g. flavonoids), showing weak prooxidant properties that may boost cellular antioxidant systems and thus act as preventive anticancer agents. Redox metal-based enzyme mimetic compounds as potential pharmaceutical interventions and sirtuins as promising therapeutic targets for age-related diseases and anti-aging strategies are discussed.

• Klíčová slova
• Aging, Antioxidants, Metals, Oxidative stress, ROS, Signaling pathways, Toxicity,
• MeSH
• antioxidancia * MeSH
• chronická nemoc MeSH
• lidé MeSH
• oxidační stres * MeSH
• reaktivní formy kyslíku MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antioxidancia * MeSH
• reaktivní formy kyslíku MeSH

Data on alkaloid interactions with the physiologically important transition metals, iron and copper, are mostly lacking in the literature. However, these interactions can have important consequences in the treatment of both Alzheimer's disease and cancer. As isoquinoline alkaloids include galanthamine, an approved drug for Alzheimer's disease, as well as some potentially useful compounds with cytostatic potential, 28 members from this category of alkaloids were selected for a complex screening of interactions with iron and copper at four pathophysiologically relevant pH and in non-buffered conditions (dimethyl sulfoxide) by spectrophotometric methods in vitro. With the exception of the salts, all the alkaloids were able to chelate ferrous and ferric ions in non-buffered conditions, but only five of them (galanthine, glaucine, corydine, corydaline and tetrahydropalmatine) evoked some significant chelation at pH 7.5 and only the first two were also active at pH 6.8. By contrast, none of the tested alkaloids chelated cuprous or cupric ions. All the alkaloids, with the exception of the protopines, significantly reduced the ferric and cupric ions, with stronger effects on the latter. These effects were mostly dependent on the number of free aromatic hydroxyls, but not other hydroxyl groups. The most potent reductant was boldine. As most of the alkaloids chelated and reduced the ferric ions, additional experimental studies are needed to elucidate the biological relevance of these results, as chelation is expected to block reactive oxygen species formation, while reduction could have the opposite effect.

• Klíčová slova
• alkaloid, chelation, copper, iron, reduction,
• MeSH
• Alzheimerova nemoc * MeSH
• chelátory chemie   MeSH
• cytostatické látky * MeSH
• dimethylsulfoxid MeSH
• galantamin MeSH
• hydroxylový radikál MeSH
• isochinoliny farmakologie   MeSH
• lidé MeSH
• měď chemie   MeSH
• reaktivní formy kyslíku MeSH
• redukční činidla MeSH
• soli MeSH
• železo chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chelátory MeSH
• cytostatické látky * MeSH
• dimethylsulfoxid MeSH
• galantamin MeSH
• hydroxylový radikál MeSH
• isochinoliny MeSH
• měď MeSH
• reaktivní formy kyslíku MeSH
• redukční činidla MeSH
• soli MeSH
• železo MeSH