The chronic exposure of skin to ultraviolet (UV) radiation causes adverse dermal reactions, such as erythema, sunburn, photoaging, and cancer, by altering several signalling pathways associated with oxidative stress, inflammation, and DNA damage. One of the possible UV light protection strategies is the use of dermal photoprotective preparations. The plant hormone kinetin (N6-furfuryladenine; KIN) exhibits antioxidant and anti-senescent effects in human cells. Topically applied KIN also reduced some of the clinical signs of photodamaged skin. To improve the biological activities of KIN, several derivatives have been recently prepared and their beneficial effects on cell viability of skin cells exposed to UVA and UVB light were screened. Two potent candidates, 6-(tetrahydrofuran-2-yl)methylamino-9-(tetrahydrofuran-2-yl)purine (HEO) and 6-(thiophen-2-yl)methylamino-9-(tetrahydrofuran-2-yl)purine (HEO6), were identified. Here the effects of KIN, its N9-substituted derivatives the tetrahydropyran-2-yl derivative of KIN (THP), tetrahydrofuran-2-yl KIN (THF), HEO and HEO6 (both THF derivatives) on oxidative stress, apoptosis and inflammation in UVA- or UVB-exposed skin cell was investigated. Human primary dermal fibroblasts and human keratinocytes HaCaT pre-treated with the tested compounds were then exposed to UVA/UVB light using a solar simulator. All compounds effectively prevented UVA-induced ROS generation and glutathione depletion in both cells. HEO6 was found to be the most potent. All compounds also reduced UVB-induced caspase-3 activity and interleukin-6 release. THP and THF exhibited the best UVB protection. In conclusion, our results demonstrated the UVA- and UVB-photoprotective potential of KIN and its derivatives. From this point of view, they seem to be useful agents for full UV spectrum protective dermatological preparations.
- MeSH
- antioxidancia farmakologie MeSH
- keratinocyty * metabolismus MeSH
- kinetin metabolismus farmakologie MeSH
- kůže * účinky záření MeSH
- lidé MeSH
- ultrafialové záření škodlivé účinky MeSH
- zánět metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Cytokinins modulate a number of important developmental processes, including the last phase of leaf development, known as senescence, which is associated with chlorophyll breakdown, photosynthetic apparatus disintegration and oxidative damage. There is ample evidence that cytokinins can slow down all these senescence-accompanying changes. Here, we review relationships between the various mechanisms of action of these regulatory molecules. We highlight their connection to photosynthesis, the pivotal process that generates assimilates, however may also lead to oxidative damage. Thus, we also focus on cytokinin induction of protective responses against oxidative damage. Activation of antioxidative enzymes in senescing tissues is described as well as changes in the levels of naturally occurring antioxidative compounds, such as phenolic acids and flavonoids, in plant explants. The main goal of this review is to show how the biological activities of cytokinins may be related to their chemical structure. New links between molecular aspects of natural cytokinins and their synthetic derivatives with antisenescent properties are described. Structural motifs in cytokinin molecules that may explain why these molecules play such a significant regulatory role are outlined.
- MeSH
- antioxidancia chemie metabolismus MeSH
- cytokininy chemie metabolismus MeSH
- flavonoidy analýza MeSH
- fotosyntéza MeSH
- listy rostlin chemie růst a vývoj fyziologie MeSH
- molekulární struktura MeSH
- rostliny chemie MeSH
- vývoj rostlin MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
UV záření (UVA a UVB), které je složkou slunečního světla dopadajícího na zemský povrch, má vysokou energii. Díky této skutečnosti může přímo reagovat s biomolekulami (DNA, lipidy nebo proteiny), případně vyvolávat tvorbu reaktivních forem kyslíku (ROS), které mohou tyto biomolekuly poškozovat, což se projeví nevratnými změnami kůže vedoucími k jejímu předčasnému stárnutí, v horším případě ke karcinogenezi. Ve snaze potlačit nežádoucí účinky slunečního záření se využívají různé přístupy ochrany kůže. Kromě anorganických a organických UV filtrů jsou zkoumány přirozeně se vyskytující nízkomolekulární látky rostlinné povahy, které mohou eliminovat nežádoucí účinky slunečního záření. Rostlinné hormony cytokininy, zejména kinetin (Kin), který je N6-substituovaným derivátem adeninu, jsou známy pro svou schopnost zpomalovat přirozené stárnutí buněk, to znamená, že vykazují tzv. antisenescenční vlastnosti. Nedávno bylo prokázáno, že některé cytokininy a jejich deriváty mají ochranné vlastnosti vůči UVA i UVB záření. Jejich využití při zpomalení předčasného stárnutí kůže působením slunečního záření je předmětem intenzivního studia.
UV radiation (UVA and UVB), is an integral part of the sunlight reaching the earth's surface containing high energy photons. Owning to the high energy, the photons they can directly interact with biomolecules like DNA, lipids, and proteins and/or generate reactive oxygen species (ROS) causing oxidative damage and irreversible changes in the skin. The changes can lead to premature skin ageing (photoageing) and even skin cancer. Adequate protection of the skin is hence of paramount importance. Exogenous protection approaches that are being developed include organic and inorganic sunscreens as well as various naturally occurring low molecular weight compounds of plant-origin. The plant hormones, cytokinins, especially kinetin (Kin), which is a N6-substituted adenine derivative, are known for their antisenescence and antioxidant effects. Some cytokinins and their derivatives, in addition, have been shown to have photoprotective properties against UVA and UVB radiation. Their application in the prevention of photoageing is being intensively studied.
Eleven 6-furfurylaminopurine (kinetin, Kin) derivatives were synthesized to obtain biologically active compounds. The prepared compounds were characterized using 1H NMR, mass spectrometry combined with HPLC purity determination and elemental C, H, N analyses. The biological activity of new derivatives was tested on plant cells and tissues in cytokinin bioassays, such as tobacco callus, detached wheat leaf chlorophyll retention bioassay and Amaranthus bioassay. The selected compounds were subsequently tested on normal human dermal fibroblasts (NHDF) and keratinocyte cell lines (HaCaT) to exclude possible phototoxic effects and, on the other hand, to reveal possible UVA and UVB photoprotective activity. The protective antioxidant activity of the prepared cytokinin derivatives was further studied and compared to previously prepared antisenescent compound 6-furfurylamino-9-(tetrahydrofuran-2-yl)purine (Kin-THF) using induced oxidative stress (OS) on nematode Caenorhabditis elegans damaged by 5-hydroxy-1,4-naphthoquinone (juglone), a generator of reactive oxygen species. The observed biological activity was interpreted in relation to the structure of the prepared derivatives. The most potent oxidative stress protection of all the prepared compounds was shown by 6-(thiophen-2-ylmethylamino)-9-(tetrahydrofuran-2-yl)purine (6) and 2-chloro-6-furfurylamino-9-(tetrahydrofuran-2-yl)purine (9) derivatives and the results were comparable to Kin-THF. Compounds 6 and 9 were able to significantly protect human skin cells against UV radiation in vitro. Both the derivatives 6 and 9 showed higher protective activity in comparison to previously known structurally similar compounds Kin and Kin-THF. The obtained results are surprising due to the fact that the prepared compounds showed to be inactive in the ORAC assay which proved that the compounds did not act as direct antioxidants as they were unable to directly scavenge oxygen radicals.
- MeSH
- cytokininy chemická syntéza chemie farmakologie MeSH
- kůže účinky léků MeSH
- lidé MeSH
- molekulární struktura MeSH
- ochranné látky chemická syntéza chemie farmakologie MeSH
- oxidační stres účinky léků MeSH
- ultrafialové záření * MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Isoprenoid cytokinins play a number of crucial roles in the regulation of plant growth and development. To study cytokinin receptor properties in plants, we designed and prepared fluorescent derivatives of 6-[(3-methylbut-2-en-1-yl)amino]purine (N6-isopentenyladenine, iP) with several fluorescent labels attached to the C2 or N9 atom of the purine moiety via a 2- or 6-carbon linker. The fluorescent labels included dansyl (DS), fluorescein (FC), 7-nitrobenzofurazan (NBD), rhodamine B (RhoB), coumarin (Cou), 7-(diethylamino)coumarin (DEAC) and cyanine 5 dye (Cy5). All prepared compounds were screened for affinity for the Arabidopsis thaliana cytokinin receptor (CRE1/AHK4). Although the attachment of the fluorescent labels to iP via the linkers mostly disrupted binding to the receptor, several fluorescent derivatives interacted well. For this reason, three derivatives, two rhodamine B and one 4-chloro-7-nitrobenzofurazan labeled iP were tested for their interaction with CRE1/AHK4 and Zea mays cytokinin receptors in detail. We further showed that the three derivatives were able to activate transcription of cytokinin response regulator ARR5 in Arabidopsis seedlings. The activity of fluorescently labeled cytokinins was compared with corresponding 6-dimethylaminopurine fluorescently labeled negative controls. Selected rhodamine B C2-labeled compounds 17, 18 and 4-chloro-7-nitrobenzofurazan N9-labeled compound 28 and their respective negative controls (19, 20 and 29, respectively) were used for in planta staining experiments in Arabidopsis thaliana cell suspension culture using live cell confocal microscopy.
- MeSH
- 4-chlor-7-nitrobenzofurazan farmakologie MeSH
- adenin analogy a deriváty chemie MeSH
- Arabidopsis metabolismus MeSH
- barvicí látky chemie MeSH
- cytokininy chemie farmakologie MeSH
- fluorescenční barviva chemie MeSH
- isopentenyladenosin chemická syntéza chemie farmakologie MeSH
- karbocyaniny chemie MeSH
- konfokální mikroskopie MeSH
- kukuřice setá metabolismus MeSH
- molekulární struktura MeSH
- proteiny huseníčku metabolismus MeSH
- puriny chemie MeSH
- receptory cytokinové antagonisté a inhibitory chemie MeSH
- regulace genové exprese u rostlin MeSH
- regulátory růstu rostlin metabolismus MeSH
- rhodaminy chemie MeSH
- semenáček metabolismus MeSH
- terpeny metabolismus MeSH
- vývoj rostlin MeSH
- Publikační typ
- časopisecké články MeSH
Perioperative ulnar neuropathies attributed to inappropriate arm positioning and padding during surgical procedures are commonly found in adults. However, their extremely rare incidence in the pediatric population may cause absent awareness of the risk of nerve injury in anesthetized pediatric patients. Furthermore, young patients respond to conservative treatment of neuropathy less favorably than adults and their response also depends on the pathomechanism of the ulnar nerve injury. A surgeon's or anesthetist's failure to recognize all of these specifics in children may result in substantial morbidity of young patients leading to lawsuits. Fortunately, with an adequate knowledge of surgical anatomy and types of procedures and positions in which the ulnar nerve is particularly vulnerable, and familiarity with measures to minimize the potential for neuropathy, this serious complication can be prevented. The aims of this review are to highlight personal experience and current knowledge of the rare position-related ulnar neuropathy, both from a clinical and anatomical-pathophysiological perspective, and to raise awareness about this rare but serious complication in the pediatric population.
Problematika pasivní bezpečnosti motocyklu a biomechaniky poranění motocyklisty se v posledních letech dostává do popředí zájmu a stává se postupně jedním z hlavních témat motocyklových výrobců. Snaha omezit závažné následky motocyklových dopravních nehod dvou víceméně nekompatibilních kolizních partnerů (motocykl – automobil) dnes vyúsťuje do evropských projektů, které mají za úkol zlepšit pasivní ochranu motocyklistů.
The problem of the passive safety of motorcycles and the biomechanics of the injuries of motorcyclists is recently gaining ground and is becoming one of the main themes of the motorcycle producers. The effort to limit the substantial consequences of the motorcycle traffic accidents of two more or less incompatible collision partners (motorcycle – car) leads to the current European projects having the task to improve the passive protection of motorcyclists.
