Tapinarof (3,5-dihydroxy-4-isopropylstilbene) is a therapeutic agent used in the treatment of psoriasis (VTAMA®). In this study, we examined the redox behaviour, (photo)stability, (photo)toxicity and (bio)transformation of tapinarof in the context of a structure-activity relationship study. Selected derivatives of the structurally related tapinarof were investigated, namely resveratrol, pterostilbene, pinosylvin and its methyl ether. Tapinarof undergoes electrochemical oxidation in a neutral aqueous medium at a potential of around +0.5 V (vs. Ag|AgCl|3M KCl). The anodic reaction of this substance is a proton-dependent irreversible and adsorption-driven process. The pKa value of tapinarof corresponds to 9.19 or 9.93, based on empirical and QM calculation approach, respectively. The oxidation potentials of tapinarof and its analogues correlate well with their HOMO (highest occupied molecular orbital) energy level. The ability to scavenge the DPPH radical decreased in the order trolox ≥ resveratrol > pterostilbene > tapinarof > pinosylvin ≫ pinosylvin methyl ether. It was also confirmed that tapinarof, being a moderate electron donor, is able to scavenge the ABTS radical and inhibit lipid peroxidation. The 4'-OH group plays a pivotal role in antioxidant action of stilbenols. During the stability studies, it was shown that tapinarof is subject to spontaneous degradation under aqueous conditions, and its degradation is accelerated at elevated temperatures and after exposure to UVA (315-399 nm) radiation. In aqueous media at pH 7.4, we observed an ∼50 % degradation of tapinarof after 48 h at laboratory temperature. The main UVA photodegradation processes include dihydroxylation and hydration. In conclusion, the phototoxic effect of tapinarof on a human keratinocytes cell line (HaCaT) was evaluated. Tapinarof exhibited a clear phototoxic effect, similar to phototoxic standard chlorpromazine. The IC50 values of the cytotoxicity and phototoxic effects of tapinarof correspond to 27.6 and 3.7 μM, respectively. The main HaCaT biotransformation products of tapinarof are sulfates and glucuronides.
- MeSH
- antioxidancia farmakologie chemie MeSH
- buněčné linie keratinocytů HaCaT MeSH
- fototoxická dermatitida MeSH
- keratinocyty * účinky léků metabolismus účinky záření MeSH
- kůže účinky léků metabolismus účinky záření patologie MeSH
- lidé MeSH
- oxidace-redukce * MeSH
- resveratrol farmakologie analogy a deriváty chemie MeSH
- stilbeny * farmakologie chemie MeSH
- ultrafialové záření MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
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
Ultrafialové (UV) záření společně s infračerveným (IR) zářením a zářením ve viditelné oblasti spektra (VIS) jsou součástí elektromagnetického záření dopadajícího na zemský povrch. UV světlo má kromě pozitivních (zejm. tvorba vitaminu D3) také nepříznivé účinky na lidský organismus. Vůči UV záření si lidská kůže během evoluce vytvořila různé obranné mechanismy, avšak jejich kapacita je, obzvláště při intenzivní expozici na slunci, omezená. Cílem tohoto článku je proto stručně představit, charakterizovat a klasifikovat (kosmetické) přípravky aktivně zamezující působení UV záření na lidskou pokožku. Tento článek dále popisuje nezbytné kroky a základní principy správné aplikace přípravků chránicích pokožku před UV zářením.
Ultraviolet (UV) radiation among with infrared (IR) radiation and the visible region of the spectrum (VIS) are part of the electromagnetic radiation reaching the Earth's surface. In addition to positive effects (e.g., synthesis of vitamin D), UV radiation also has an adverse impact on the human body, such as cancerous proliferation. During evolution, human skin has developed various protecting mechanisms against UV (e.g., melanin pigment), but their capacity is limited (especially during intensive exposure to the sun). Therefore, this article aims to present, characterize, and classify (cosmetic) products that actively prevent the effects of UV radiation on human skin. This article also describes the necessary steps and basic principles for the proper application of these products.
- MeSH
- kůže účinky záření MeSH
- lidé MeSH
- ochranný sluneční faktor MeSH
- přípravky chránící proti slunci * chemie terapeutické užití MeSH
- ultrafialové záření MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- hojení ran účinky záření MeSH
- kontraindikace MeSH
- kůže účinky záření MeSH
- lidé MeSH
- obvazy klasifikace MeSH
- radiační poranění * etiologie farmakoterapie klasifikace MeSH
- radioterapie škodlivé účinky MeSH
- sloučeniny stříbra * terapeutické užití MeSH
- vztah dávky záření a odpovědi MeSH
- Check Tag
- lidé MeSH
Some vegetable oils are currently being promoted as a safe alternative to commercial sunscreens. The true UVB photoprotective efficacy of 14 virgin vegetable oils and the suitability of the dilution method for determining their SPF value were evaluated. Oils and standard sunscreens were investigated in vitro by the Mansur's method in Slovakia and in vivo by the ISO method in the Czech Republic. SPF values in vitro (0.1; 0.0; 0.4; 0.2 and 0.2) and in vivo (2.5; 1.2; 2.6; 2.6; and 2.8) of the five most promoted oils (from carrot seed, coconut, raspberry seed, rosehip seed, and wheat germ) were significantly lower than the values reported in the controversial studies. We have shown that the overestimated SPF values of these oils were determined by authors who did not strictly follow Mansur's original methodology. The other eight vegetable oils also provide no or negligible SPF values. Only the in vitro SPF value of 11.2 tamanu oil is worth mentioning, probably due to high proportion of calophyllolides. In vitro and in vivo SPF ratios from 1.14 to 0.94 obtained by two methods in two laboratories for six commercial sunscreen oils used as controls confirm the correctness of performing the Mansur's method in this study. However, this dilution method has proven to be fundamentally flawed in determining the SPF value of substances with such negligible photoprotection as most vegetable oils can provide. An SPF value of less than 1, which can be determined by this Mansur's method, is physiologically impossible and meaningless.
- MeSH
- benzimidazoly chemie MeSH
- dospělí MeSH
- kůže účinky záření MeSH
- lidé středního věku MeSH
- lidé MeSH
- ochranný sluneční faktor MeSH
- oleje rostlin chemie MeSH
- přípravky chránící proti slunci chemie MeSH
- Rubus chemie metabolismus MeSH
- semena rostlinná chemie metabolismus MeSH
- senioři MeSH
- ultrafialové záření * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Adjuvantní radioterapie je velmi častou součástí léčby non-metastatického nádoru prsu. Přestože je tato léčba velmi účinná, je zatížena nežádoucími účinky, které u části pacientek mohou vést zejména k neakceptovatelnému zvýšení kardiovaskulárního rizika, ale také k rostoucímu riziku rozvoje sekundární malignity. Protonová radioterapie díky svým dozimetrickým výhodám přináší možnost snížení integrální dávky, dávky na rizikové orgány a současně umožňuje zachovat optimální pokrytí cílového objemu. Tato výhoda stoupá s rostoucí komplexností cílového objemu (např. při indikaci k ozáření vnitřních mamárních uzlin) a u mladších pacientek s levostranným karcinomem prsu. Dostupná klinická data prokazují její proveditelnost i absenci neočekávaných nežádoucích účinků. Probíhající klinické studie a sběr dat v rámci follow-up potom nabídnou možnost upřesnění kritérií, na základě kterých by měly být pacientky k protonové radioterapii referovány.
Adjuvant iradiation is frequently used for treatment of non-metastatic breast cancer patients. Althought photon irradiation improved local control and overal survival, its use could lead to unacceptable increas of cardiovascular toxicity or secondary cancer risk. Proton therapy due to its dosimetric advanatages compared to photon radioterapy decreases the integral dose, dose to organs at risk and at the same time allows optimal coverage of the treatment volume. This advantage is more evident in more complex volumes, like in cases where internal mammary nodes have to be irradiated, and in younger patients with left-sided breast cancer. Available early clinical data confirms that proton irradiation is feasbile and not connected with unacceptable or unexpected risk of complications. Ongoing clinical trials and data collection during the follow-up will lead to identification of prognostic factors, which could help in identifying of patients, who will most benefit from proton radioterapy use.
- MeSH
- dávka záření MeSH
- fotony terapeutické užití MeSH
- karcinom radioterapie MeSH
- kůže účinky záření MeSH
- lidé MeSH
- nádory prsu * radioterapie MeSH
- protonová terapie * ošetřování škodlivé účinky MeSH
- radioterapie metody ošetřování škodlivé účinky MeSH
- riziko MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- srdce účinky záření MeSH
- výběr pacientů MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
The harmful effects of low energy UVA photons (315-400 nm) are associated with the massive production of reactive oxygen species resulting in oxidative stress. In response to oxidative damage, NF-E2-related factor 2 (Nrf2) is translocated to the nucleus and drives the expression of detoxication and antioxidant enzymes. UVA's effect on Nrf2 has been quite well characterised in dermal fibroblasts. However, there is a dearth of such information for keratinocytes. This study aimed to evaluate and compare the effect of UVA radiation on the Nrf2 pathway and oxidative stress related proteins in primary human dermal fibroblasts (NHDF), epidermal keratinocytes (NHEK) and human keratinocyte cell line HaCaT. NHDF were exposed to doses of 2.5-7.5 J/cm2, NHEK and HaCaT to 10-20 J/cm2 using a solar simulator. Effects on Nrf2 translocation were evaluated after 1, 3 and 6 h and Nrf2-controlled proteins (heme oxygenase 1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione reductase (GSR), glutathione-S-transferase (GST), interleukine-6 (IL-6), and matrix metalloproteinases (MMP-1, MMP-2)) after 3, 6 and 24 h. The results showed the fastest Nrf2 translocation was in UVA-irradiated HaCaT (1 h), persisting until the subsequent time interval (3 h), while in primary keratinocytes the effect of radiation was minimal. In NHDF, UVA-stimulated Nrf2 translocation was conspicuous 3 h after UVA treatment. In NHDF, most of the studied proteins (NQO1, HO-1, GSR, GSTM1 and MMP-1) showed the highest level 24 h after UVA exposure, except for MMP-2 and IL-6 which had their highest level at a shorter time incubation interval (3 h). In NHEK, NQO1, HO-1 and GST were increased 6 h after UVA exposure, GSR and MMP-2 level was slightly below or above the control level, and MMP-1 and IL-6 increased at shorter time intervals. When comparing NHEK and HaCaT, these cells displayed contrary responses in most of the Nrf2-controlled proteins. Thus, primary keratinocytes cannot be replaced with HaCaT when studying cell signalling such as the Nrf2 driven pathway and Nrf2-controlled proteins.
- MeSH
- faktor 2 související s NF-E2 metabolismus MeSH
- keratinocyty metabolismus účinky záření MeSH
- kultivované buňky MeSH
- kůže cytologie metabolismus účinky záření MeSH
- lidé MeSH
- signální transdukce účinky záření MeSH
- transport proteinů MeSH
- ultrafialové záření * MeSH
- viabilita buněk účinky záření MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
AIMS: The aim of this investigator-initiated prospective randomized open-label single institutional trial is to evaluate the role of acupuncture in the treatment of acute skin and mucosal toxicity, xerostomia, and perception of taste, pain, and nausea related to curative and adjuvant (chemo)radiotherapy of head and neck cancer. This paper reports pilot data of the first 30 enrolled patients. METHODS: Patients were randomized to undergo standard of care radiotherapy ± chemotherapy and support care defined by our institutional standard operating procedures alone or in the combination with acupuncture which was initiated with the first signs of any toxicity. RESULTS: Fifteen patients were enrolled in both arms and all finished the treatment as planned.The median pain was significantly lower in the acupuncture arm (median 1.6 points vs. 2.5 points on a 10-item Likert scale; P=0.035) as well as duration of acute pain (median 31 days vs. 54 days; P=0.031). Patients with acupuncture had significantly shorter duration of acute skin (median 44 days vs. 109 days; P<0.001) and mucosal toxicity (median 34 days vs. 109 days; P<0.001) with no difference in grading of toxicity (median grade 1.6 vs. 1.5; P=0.701 and median grade 1.4 vs. 1.6; P=0.204 for skin and mucosa, respectively). No significant difference was found for other toxicity domains, with the exception of salivation toxicity which was significantly lower in acupuncture arm (median grade 1.3 vs. 1.7; P=0.048). CONCLUSION: In this interim analysis, acupuncture leads to lower pain andfaster disappearance of skin and mucosal toxicity after (chemo)radiotherapy of head and neck cancer. Description and validation of acupuncture using scientific approaches will further enhance acceptance of this method by both patients and health care providers. TRIAL REGISTRATION: Clinicaltrials.gov - NCT03751566.
- MeSH
- akupunkturní terapie metody MeSH
- kožní nemoci etiologie terapie MeSH
- kůže účinky záření MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory hlavy a krku radioterapie MeSH
- prospektivní studie MeSH
- radioterapie škodlivé účinky MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Onkologická léčba je léčbou komplexní. Její protinádorová účinnost se zvyšuje díky po-užívání moderních metod léčby, nicméně s tím se ruku v ruce zvyšují její nežádoucí účinky, které se mohou projevit též na kůži v podobě kožních poškození různého stupně. Nežádoucí účinky onkologické léčby je možné mírnit, léčit a někdy řešit již v profylaxi díky zlepšující se podpůrné terapii. Velkým problémem onkologie však zůstávají maligní rány, jejichž léčba je velmi obtížná až nemožná a je zaměřená většinou na průvodní symptomy.
Anticancer treatment is a complex therapy. Its anticancer efficacy inreases thank to using of modern methods of tretment but adverse effects including dermatological also grow. We can find derma-tological injury of different grades. It is possible to treat, cure or prevent them with methods of supporive care. Malignant ulcerations (injuries) stays big problems in onkology becouse their treatment is targeted to symptoms.
- Klíčová slova
- radiokurabilita, deskvamace,
- MeSH
- biologická terapie škodlivé účinky MeSH
- cytostatické látky škodlivé účinky MeSH
- kožní manifestace MeSH
- krev účinky záření MeSH
- kůže patologie účinky záření MeSH
- lidé MeSH
- nádory * farmakoterapie radioterapie MeSH
- nežádoucí účinky léčiv * farmakoterapie patofyziologie patologie prevence a kontrola MeSH
- radiodermatitida chemicky indukované farmakoterapie patofyziologie patologie prevence a kontrola MeSH
- radioterapie metody škodlivé účinky MeSH
- rány a poranění chemicky indukované patologie terapie MeSH
- syndrom ruka-noha MeSH
- tolerance záření MeSH
- tyrosinkinasy antagonisté a inhibitory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
