Dual Role of Stratum Corneum Carotenes/Lycopene Against the Development of Chemotherapy-induced PPE in Patients With Cancer.

Palmar-plantar erythrodysaesthesia (PPE) is a common side effect of chemotherapy treatment in patients with cancer. The exact pathophysiologic mechanisms of the development of PPE remain unclear. Here, we report two important physiological functions of carotenoids without hydroxyl groups (α-carotene, ß-carotene, γ-carotene, ξ-carotene, lycopene, phytoene, phytofluene and their isomers) in the stratum corneum (SC) of glabrous skin: The powerful antioxidant protection of the integrity of the SC components against the destructive action of free radicals and maintaining the skin barrier function by the creation of an orthorhombic organization of intercellular lipids within lamellae using carotenoids as a skeleton. The dual protective role of carotenoids without hydroxyl groups is important for both healthy skin and, in the authors' opinion, for the skin of chemotherapy-treated patients against the development of PPE, as the chemotherapy-induced reduction of the carotenoid concentration in the stratum corneum considerably weakens the skin resistance to cytotoxic and other adverse reactions.

Two-Photon-Excited FLIM of NAD(P)H and FAD-Metabolic Activity of Fibroblasts for the Diagnostics of Osteoimplant Survival.

Bioinert materials such as the zirconium dioxide and aluminum oxide are widely used in surgery and dentistry due to the absence of cytotoxicity of the materials in relation to the surrounding cells of the body. However, little attention has been paid to the study of metabolic processes occurring at the implant-cell interface. The metabolic activity of mouse 3T3 fibroblasts incubated on yttrium-stabilized zirconium ceramics cured with aluminum oxide (ATZ) and stabilized zirconium ceramics (Y-TZP) was analyzed based on the ratio of the free/bound forms of cofactors NAD(P)H and FAD obtained using two-photon microscopy. The results show that fibroblasts incubated on ceramics demonstrate a shift towards the free form of NAD(P)H, which is observed during the glycolysis process, which, according to our assumptions, is related to the porosity of the surface of ceramic structures. Consequently, despite the high viability and good proliferation of fibroblasts assessed using an MTT test and a scanning electron microscope, the cells are in a state of hypoxia during incubation on ceramic structures. The FLIM results obtained in this work can be used as additional information for scientists who are interested in manufacturing osteoimplants.

Impact of e-cigarette liquid on porcine lung tissue-Ex vivo confocal Raman micro-spectroscopy study.

Ex vivo porcine lung immersed in e-liquid was investigated in-depth using confocal Raman micro-spectroscopy to assess the e-liquid influence on the lung. It was found that lung-related Raman band intensities at 1002, 1548, 1618 and 1655 cm-1 increased after first and second treatments except the surface, which was attributed to the well-known optical clearing (OC) effect due to alveoli filling with e-liquid resulting in light scattering reduction. The autofluorescence enhancement was explained by oxidative stress induced in lung during exposure to e-liquid. Moreover, e-liquid induced collagen dehydration was revealed by the I937 /I926 Raman band intensity ratio change. The effect was enhanced after the second treatment of the same lung tissue that indicates the possibility of multi-step OC treatment. We hypothesize that the nicotine-flavour-free e-liquids containing glycerol and propylene glycol could potentially be used in clinical protocols as OC agent for enhanced in-depth Raman-guided bronchoscopy.

Atopic Dermatitis: Molecular Alterations between Lesional and Non-Lesional Skin Determined Noninvasively by In Vivo Confocal Raman Microspectroscopy.

Atopic dermatitis (AD)/atopic eczema is a chronic relapsing inflammatory skin disease affecting nearly 14% of the adult population. An important pathogenetic pillar in AD is the disrupted skin barrier function (SBF). The atopic stratum corneum (SC) has been examined using several methods, including Raman microspectroscopy, yet so far, there is no depth-dependent analysis over the entire SC thickness. Therefore, we recruited 21 AD patients (9 female, 12 male) and compared the lesional (LAS) with non-lesional atopic skin (nLAS) in vivo with confocal Raman microspectroscopy. Our results demonstrated decreased total intercellular lipid and carotenoid concentrations, as well as a shift towards decreased orthorhombic lateral lipid organisation in LAS. Further, we observed a lower concentration of natural moisturising factor (NMF) and a trend towards increased strongly bound and decreased weakly bound water in LAS. Finally, LAS showed an altered secondary and tertiary keratin structure, demonstrating a more folded keratin state than nLAS. The obtained results are discussed in comparison with healthy skin and yield detailed insights into the atopic SC structure. LAS clearly shows molecular alterations at certain SC depths compared with nLAS which imply a reduced SBF. A thorough understanding of these alterations provides useful information on the aetiology of AD and for the development/control of targeted topical therapies.

Red- and Near-Infrared-Excited Autofluorescence as a Marker for Acute Oxidative Stress in Skin Exposed to Cigarette Smoke Ex Vivo and In Vivo.

Air pollution is increasing worldwide and skin is exposed to high levels of pollution daily, causing oxidative stress and other negative consequences. The methods used to determine oxidative stress in the skin are invasive and non-invasive label-free in vivo methods, which are severely limited. Here, a non-invasive and label-free method to determine the effect of cigarette smoke (CS) exposure on skin ex vivo (porcine) and in vivo (human) was established. The method is based on the measurement of significant CS-exposure-induced enhancement in red- and near-infrared (NIR)-excited autofluorescence (AF) intensities in the skin. To understand the origin of red- and NIR-excited skin AF, the skin was exposed to several doses of CS in a smoking chamber. UVA irradiation was used as a positive control of oxidative stress in the skin. The skin was measured with confocal Raman microspectroscopy before CS exposure, immediately after CS exposure, and after skin cleaning. CS exposure significantly increased the intensity of red- and NIR-excited skin AF in a dose-dependent manner in the epidermis, as confirmed by laser scanning microscopy AF imaging and fluorescence spectroscopy measurements. UVA irradiation enhanced the intensity of AF, but to a lower extent than CS exposure. We concluded that the increase in red- and NIR-excited AF intensities of the skin after CS exposure could clearly be related to the induction of oxidative stress in skin, where skin surface lipids are mainly oxidized.

Tattoo Pigments Are Localized Intracellularly in the Epidermis and Dermis of Fresh and Old Tattoos: In vivo Study Using Two-Photon Excited Fluorescence Lifetime Imaging.

BACKGROUND: The knowledge about the location and kinetics of tattoo pigments in human skin after application and during the recovery is restricted due to the limitation of in vivo methods for visualizing pigments. Here, the localization and distribution of tattoo ink pigments in freshly and old tattooed human skin during the regeneration of the epidermis and dermis were investigated in vivo. METHODS: Two-photon excited fluorescence lifetime imaging (TPE-FLIM) was used to identify tattoo ink pigments in human skin in vivo down to the reticular dermis. One subject with a freshly applied tattoo and 10 subjects with tattoos applied over 3 years ago were investigated in the epidermal and dermal layers in vivo. One histological slide of tattooed skin was used to localize skin-resident tattoo pigment using light microscopy. RESULTS: The carbon black particles deposited around the incision have still been visible 84 days after tattoo application, showing delayed recovery of the epidermis. The TPE-FLIM parameters of carbon black tattoo ink pigments were found to be different to all skin components except for melanin. Distinction from melanin in the skin was based on higher fluorescence intensity and agglomerate size. Using TPE-FLIM in vivo tattoo pigment was found in 75% of tattoos applied up to 9 years ago in the epidermis within keratinocytes, dendritic cells, and basal cells and in the dermis within the macrophages, mast cells, and fibroblasts. Loading of highly fluorescent carbon black particles enables in vivo imaging of dendritic cells in the epidermis and fibroblasts in the dermis, which cannot be visualized in native conditions. The collagen I structures showed a higher directionality similar to scar tissue resulting in a greater firmness and decreased elasticity of the tattooed skin. CONCLUSIONS: Here, we show the kinetics and location of carbon black tattoo ink pigment immediately after application for the first time in vivo in human skin. Carbon black particles are located exclusively intracellularly in the skin of fresh and old tattoos. They are found within macrophages, mast cells, and fibroblasts in the dermis and within keratinocytes, dendritic cells, and basal cells in the continuously renewed epidermis even in 9-year-old tattoos in skin showing no inflammation.

Label-free imaging of M1 and M2 macrophage phenotypes in the human dermis in vivo using two-photon excited FLIM.

Macrophages (ΜΦs) are important immune effector cells that promote (M1 ΜΦs) or inhibit (M2 ΜΦs) inflammation and are involved in numerous physiological and pathogenic immune responses. Their precise role and relevance, however, are not fully understood for lack of noninvasive quantification methods. Here, we show that two-photon excited fluorescence lifetime imaging (TPE-FLIM), a label-free noninvasive method, can visualize ΜΦs in the human dermis in vivo. We demonstrate in vitro that human dermal ΜΦs exhibit specific TPE-FLIM properties that distinguish them from the main components of the extracellular matrix and other dermal cells. We visualized ΜΦs, their phenotypes and phagocytosis in the skin of healthy individuals in vivo using TPE-FLIM. Additionally, machine learning identified M1 and M2 MФs with a sensitivity of 0.88±0.04 and 0.82±0.03 and a specificity of 0.89±0.03 and 0.90±0.03, respectively. In clinical research, TPE-FLIM can advance the understanding of the role of MФs in health and disease.

Carotenoids in Human SkinIn Vivo: Antioxidant and Photo-Protectant Role against External and Internal Stressors.

The antioxidant system of the human body plays a crucial role in maintaining redox homeostasis and has an important protective function. Carotenoids have pronounced antioxidant properties in the neutralization of free radicals. In human skin, carotenoids have a high concentration in the stratum corneum (SC)-the horny outermost layer of the epidermis, where they accumulate within lipid lamellae. Resonance Raman spectroscopy and diffuse reflectance spectroscopy are optical methods that are used to non-invasively determine the carotenoid concentration in the human SC in vivo. It was shown by electron paramagnetic resonance spectroscopy that carotenoids support the entire antioxidant status of the human SC in vivo by neutralizing free radicals and thus, counteracting the development of oxidative stress. This review is devoted to assembling the kinetics of the carotenoids in the human SC in vivo using non-invasive optical and spectroscopic methods. Factors contributing to the changes of the carotenoid concentration in the human SC and their influence on the antioxidant status of the SC in vivo are summarized. The effect of chemotherapy on the carotenoid concentration of the SC in cancer patients is presented. A potential antioxidant-based pathomechanism of chemotherapy-induced hand-foot syndrome and a method to reduce its frequency and severity are discussed.

In vivo Skin Penetration, Radical Protection, and Structural Changes after Topical Application of a Herbal Oil Cream Compared to Topical Calcipotriol in Mild to Moderate Psoriasis.

BACKGROUND: The chronicity of psoriasis often requires continuous topical treatment. MATERIALS AND METHODS: Here, the radical protection of a cream containing various herbal oils was evaluated in vivo by electron paramagnetic resonance (EPR) spectroscopy and its skin penetration by Raman microscopy in intact and barrier-disturbed skin. Changes in skin barrier properties were evaluated after 4 weeks of daily topical application using in vivo laser scanning microscopy (LSM) and transepidermal water loss in 26 healthy volunteers. A randomized, controlled, double-blind, three-arm parallel clinical study evaluated the efficacy of the herbal oil cream compared to a 0.05% calcipotriol-containing cream and to a vehicle cream, in 135 patients with mild to moderate plaque psoriasis with the change in Psoriasis Area and Severity Index (PASI) from baseline to week 12 as the primary endpoint. RESULTS: EPR spectroscopy disclosed a significantly higher radical formation in untreated than skin treated with the herbal oil cream (p ≤ 0.05). LSM measurements indicated a protective skin barrier effect in treated compared to untreated skin. In the clinical trial, the topical application of herbal oils showed a significant reduction of the PASI score compared to topical calcipotriol at week 12 (p = 0.016). The mean reduction in PASI was 49% for the herbal oil cream, 38% for calcipotriol, and 55% for the vehicle cream. The percentage of patients, who reached PASI 50 and 75 at any time point, was 55.9% and 29.4% for the herbal oil cream, 47.4% and 15.8% for calcipotriol, and 23 (60.5%) and 13 (34.2%) for the vehicle, respectively (p > 0.05). The vehicle, originally designed as a placebo, contained a main ingredient of the herbal oil cream and therefore showed corresponding results. CONCLUSION: The herbal oil cream demonstrated effectiveness in the treatment of mild to moderate plaque psoriasis.

Release of the model drug SR101 from polyurethane nanocapsules in porcine hair follicles triggered by LED-derived low dose UVA light.

Hair follicles (HFs) are important drug delivery targets for the therapy of miscellaneous skin diseases and for skin antisepsis. Furthermore, HFs significantly contribute to drug delivery of topically applied substances. Nanoparticulate systems are excellently suited for follicular drug delivery as they entail the opportunity of directed drug transport into HFs. Moreover, they involve the possibility of an intrafollicular drug release initiated by extrinsic or intrinsic trigger mechanisms. In this study, we present a novel preclinical model for an anatomically and temporally targeted intrafollicular drug release. In vitro release kinetics of the model drug sulforhodamine 101 (SR101) from newly synthesized ultraviolet A (UVA)-responsive polyurethane nanocapsules (NCs) were investigated by fluorescence spectroscopy. Low power density UVA radiation provided by a UVA light emitting diode (LED) induced a drug release of over 50% after 2 min. We further utilized confocal laser scanning microscopy (CLSM) to investigate follicular penetration as well as intrafollicular drug release on an ex vivo porcine ear skin model. UVA-responsive degradation of the NCs at a mean follicular penetration depth of 509 ± 104 µm ensured liberation of SR101 in the right place and at the right time. Thus, for the first time a UVA-triggered drug release from NCs within HFs was demonstrated in the present study. Cytotoxicity tests revealed that NCs synthesized with isophorone diisocyanate show sufficient biocompatibility after UVA-induced cleavage. A considerable and controllable release of various water-soluble therapeutics could be reached by means of the presented system without risking any radiation-related tissue damage. Therefore, the implementation of the presented system into clinical routine, e.g. for preoperative antisepsis of HFs, appears very promising.

Kinetics of the carotenoid concentration degradation of smoothies and their influence on the antioxidant status of the human skin in vivo during 8 weeks of daily consumption.

The antioxidant status of the skin shows constant alterations depending on nutrition and other lifestyle factors. Carotenoids can serve as marker substances for the antioxidant status of the epidermis in vivo. The carotenoid concentration of 2 homemade green smoothies and a commercial green smoothie, all containing fruits and vegetables, was assessed by resonance Raman spectroscopy. Furthermore, a pilot study was conducted to investigate changes of the cutaneous carotenoid concentration of 20 healthy volunteers under the daily intake of either a homemade smoothie or the commercial smoothie in vivo using reflectance spectroscopy. We hypothesized that higher carotenoid concentrations in the homemade smoothies compared to those of the commercial one would lead to a faster increase of the cutaneous carotenoid concentration in healthy volunteers. The measurements of the homemade smoothies showed notably higher initial carotenoid concentrations (7.6 ±0.8)*10-4arbitrary units (a.u.) (smoothie A) and (10.4 ± 0.6)*10-4 a.u. (smoothie B) compared to the commercial smoothie (5.8 ± 0.2)*10-4 a.u. Nevertheless, the commercial smoothie showed a higher stability of carotenoids over 24 hours. 8 weeks after daily consumption of the homemade smoothies, volunteers showed an insignificant increase of cutaneous carotenoids from (4.5 ± 0.1)*10-4 a.u. at baseline to (4.8 ± 0.3)*10-4 a.u. (means ± standard error of the mean). The volunteers consuming the commercial smoothie showed an insignificant increase of cutaneous carotenoids from (4.3 ± 0.2)*10-4 a.u. to (4.7 ± 0.2)*10-4 a.u. after 8 weeks. The observed increase of cutaneous carotenoid concentrations could be classified as a strong tendency. Fresh homemade smoothies can exhibit a higher carotenoid concentration compared to commercial smoothies but need to be consumed immediately after preparation.

Determination of the pH Gradient in Hair Follicles of Human Volunteers Using pH-Sensitive Melamine Formaldehyde-Pyranine Nile Blue Microparticles.

Nanoparticles can be applied to the hair follicles, which can serve as reservoirs for triggered drug release. A valid measurement method for the determination of the pH within the hair follicle in vivo has not been shown yet. Here, melamine formaldehyde particles up to 9 µm in size were applied on 40 freshly plucked scalp hairs of eight individuals to determine the pH along the hair shaft down to the root area of the hair. For fluorescent pH indicators, pyranine and Nile blue were incorporated into the particles. Measurements were conducted using confocal laser scanning microscopy. A pH decay gradient could be found from the hair sheath towards the external hair shaft (p = 0.012) with pH values at the hair sheath of 6.63 ± 0.09, at the hair sheath end at 6.33 ± 0.11, and at the external hair shaft at 6.17 ± 0.09 (mean ± SE). The pH difference between the hair sheath end and the external hair shaft was found to be significant (p = 0.036). The results might be comparable with the pH within the hair follicle in vivo indicating a pH increase towards the hair root.

In vivo non-invasive staining-free visualization of dermal mast cells in healthy, allergy and mastocytosis humans using two-photon fluorescence lifetime imaging.

Mast cells (MCs) are multifunctional cells of the immune system and are found in skin and all major tissues of the body. They contribute to the pathology of several diseases including urticaria, psoriasis, atopic dermatitis and mastocytosis where they are increased at lesional sites. Histomorphometric analysis of skin biopsies serves as a routine method for the assessment of MC numbers and their activation status, which comes with major limitations. As of now, non-invasive techniques to study MCs in vivo are not available. Here, we describe a label-free imaging technique to visualize MCs and their activation status in the human papillary dermis in vivo. This technique uses two-photon excited fluorescence lifetime imaging (TPE-FLIM) signatures, which are different for MCs and other dermal components. TPE-FLIM allows for the visualization and quantification of dermal MCs in healthy subjects and patients with skin diseases. Moreover, TPE-FLIM can differentiate between two MC populations in the papillary dermis in vivo-resting and activated MCs with a sensitivity of 0.81 and 0.87 and a specificity of 0.85 and 0.84, respectively. Results obtained on healthy volunteers and allergy and mastocytosis patients indicate the existence of other MC subpopulations within known resting and activated MC populations. The developed method may become an important tool for non-invasive in vivo diagnostics and therapy control in dermatology and immunology, which will help to better understand pathomechanisms involving MC accumulation, activation and degranulation and to characterize the effects of therapies that target MCs.

Response to comment by Puppels et al. on "A modification for the calculation of water depth profiles in oil-treated skin by in vivo Raman microscopy".

The presence of penetrated oils in the stratum corneum (SC), oil-induced occlusion of the SC and formation of occluding homogeneous film on the skin surface are discussed in relation to their influence on results of water profile calculations using conventional and newly proposed extended methods. It is shown that the conventional method does not determine the water profiles in treated skin correctly due to the superposition of Raman bands of SC's proteins and penetrated and remnant oils.

In vivo detection of changes in cutaneous carotenoids after chemotherapy using shifted excitation resonance Raman difference and fluorescence spectroscopy.

BACKGROUND: Various cutaneous toxicities under chemotherapy indicate a local effect of chemotherapy by secretion after systemic application. Here, changes in the fluorescence and Raman spectral properties of the stratum corneum subsequent to intravenous chemotherapy were assessed. METHODS: Twenty healthy subjects and 20 cancer patients undergoing chemotherapy were included. Measurement time points in cancer patients were before the first cycle of chemotherapy (Tbase ) and immediately after intravenous application of the chemotherapy (T1 ). Healthy subjects were measured once without any further intervention. Measurements were conducted using an individually manufactured system consisting of a handheld probe and a wavelength-tunable diode laser-based 488 nm SHG light source. Hereby, changes in both skin fluorescence and shifted excitation resonance Raman difference spectroscopy (SERRDS) carotenoid signals were assessed. RESULTS: Healthy subjects showed significantly (P < .001) higher mean concentrations of carotenoids compared to cancer subjects at Tbase . An increase in fluorescence intensity was detected in almost all patients after chemotherapy, especially after doxorubicin infusion. Furthermore, a decrease in the carotenoid concentration in the skin after chemotherapy was found. CONCLUSION: The SERRDS based noninvasive detection can be used as an indirect quantitative assessment of fluorescent chemotherapeutics. The lower carotenoid SERRDS intensities at Tbase might be due to cancerous diseases and co-medication.

A modification for the calculation of water depth profiles in oil-treated skin by in vivo confocal Raman microscopy.

In this study, an extended calculation method for the determination of the water profiles in oil-treated skin is proposed, which is based on the calculation of the ratio between the Raman band intensities of water (3350-3550 cm-1 ) and keratin Amide I at 1650 cm-1 . The proposed method is compared with the conventional method based on the ratio of the Raman band intensities of water (3350-3550 cm-1 ) and keratin at 2930 cm-1 . The conventional method creates artifacts in the depth profiles of the water concentration in oil-treated skin, showing a lower amount of water in the upper and intermediate layers of the stratum corneum, which is due to the superposition of oil- and keratin-related Raman bands at 2930 cm-1 . The proposed extended method shows no artifacts and has the potential to determine the water depth profiles after topical application of formulations on the skin.

Nonscanning large-area Raman imaging for ex vivo/in vivo skin cancer discrimination.

Imaging Raman spectroscopy can be used to identify cancerous tissue. Traditionally, a step-by-step scanning of the sample is applied to generate a Raman image, which, however, is too slow for routine examination of patients. By transferring the technique of integral field spectroscopy (IFS) from astronomy to Raman imaging, it becomes possible to record entire Raman images quickly within a single exposure, without the need for a tedious scanning procedure. An IFS-based Raman imaging setup is presented, which is capable of measuring skin ex vivo or in vivo. It is demonstrated how Raman images of healthy and cancerous skin biopsies were recorded and analyzed.

Keratin-water-NMF interaction as a three layer model in the human stratum corneum using in vivo confocal Raman microscopy.

The secondary and tertiary structure of keratin and natural moisturizing factor (NMF) are of great importance regarding the water regulating functions in the stratum corneum (SC). In this in vivo study, the depth-dependent keratin conformation and its relationship to the hydrogen bonding states of water and its content in the SC, are investigated using confocal Raman microscopy. Based on the obtained depth-profiles for the ß-sheet/α-helix ratio, the stability of disulphide bonds, the amount of cysteine forming disulphide bonds, the buried/exposed tyrosine and the folding/unfolding states of keratin, a "three layer model" of the SC, regarding the keratin-water-NMF interaction is proposed. At the uppermost layers (30-0% SC depth), the keratin filaments are highly folded, entailing limited water binding sites, and NMF is mostly responsible for binding water. At the intermediate layers (70-30% SC depth), the keratin filaments are unfolded, have the most water binding sites and are prone to swelling. At the bottom layers (100-80% SC depth), the water binding sites are already occupied with water and cannot swell substantially. The hydrogen bonding states of water molecules can only be explained by considering both, the molecular structure of keratin and the contribution of NMF as a holistic system.

A Randomized Controlled Trial of Green Tea Beverages on the in vivo Radical Scavenging Activity in Human Skin.

BACKGROUND: Oxidative stress plays an important role in the pathogenesis of various skin diseases. Thus, the antioxidant network of the skin relies on the uptake of exogenous antioxidants to ensure cell protection against radical formation. Green tea is one of the main sources of polyphenolic antioxidant compounds, but only few data are available on its cutaneous antioxidant effects. METHODS: The radical scavenging properties of Benifuuki and Yabukita green tea were investigated in the human skin. Thirty-two participants who met the inclusion criteria were randomized to consume 3 cups per day of either Benifuuki tea, Yabukita tea, or water (control group) for 2 weeks. Electron paramagnetic resonance (EPR) spectroscopy was applied to measure the radical scavenging capacity of the skin in vivo before and after the intervention. RESULTS: Both Yabukita and Benifuuki tea led to an increase in the radical scavenging activity of the skin by 28 and 29%, respectively, and the difference was significant when compared to the control group. Benifuuki tea, previously reported to be superior in bioavailability due to a highly absorbable methylated catechin, did not prove to be more effective than the common Yabukita tea. CONCLUSION: The results show that green tea enhances the radical scavenging capacity of the skin and support the hypothesis that green tea may offer protection against cutaneous oxidative stress.

Influence of Chemotherapy on the Antioxidant Status of Human Skin.

BACKGROUND: Palmoplantar erythrodysesthesia is a frequent dermal side-effect during chemotherapy. Previous investigations showed radical formation subsequent to doxorubicin infusion and preventative and therapeutic effects of an antioxidant-containing ointment. PATIENTS AND METHODS: Using a non-invasive vivomeasuring system (Biozoom®; Biozoom Services GmbH, Kassel, Germany) changes in the antioxidant status (as measured by relative carotenoid concentration) of the skin prior to and after intravenous administration of paclitaxel, docetaxel and 5-fluorouracil were investigated in 42 patients with cancer. RESULTS: A significant decrease of antioxidant concentration subsequent to intravenous administration was found for all investigated chemotherapeutic agents. The mean concentration of carotenoids decreased from 3.59±1.26 arbitrary units (a.u.) to 3.41±1.28 a.u. (p<0.001) after paclitaxel administration, from 6.33±2.43 to 5.63±2.29 a.u. after docetaxel (p=0.027) and from 4.26±1.81 to 3.98±1.53 a.u. (p=0.042) after 5-fluorouracil infusion. CONCLUSION: Oxidative stress might play a significant role in the pathomechanism of palmoplantar erythrodysesthesia associated with paclitaxel, docetaxel and 5-fluorouracil. Therefore, an antioxidant-containing ointment might serve as preventative and therapeutic option.