Cyanobacteria Secondary Metabolites as Biotechnological Ingredients in Natural Anti-Aging Cosmetics: Potential to Overcome Hyperpigmentation, Loss of Skin Density and UV Radiation-Deleterious Effects.

The loss of density and elasticity, the appearance of wrinkles and hyperpigmentation are among the first noticeable signs of skin aging. Beyond UV radiation and oxidative stress, matrix metalloproteinases (MMPs) assume a preponderant role in the process, since their deregulation results in the degradation of most extracellular matrix components. In this survey, four cyanobacteria strains were explored for their capacity to produce secondary metabolites with biotechnological potential for use in anti-aging formulations. Leptolyngbya boryana LEGE 15486 and Cephalothrix lacustris LEGE 15493 from freshwater ecosystems, and Leptolyngbya cf. ectocarpi LEGE 11479 and Nodosilinea nodulosa LEGE 06104 from marine habitats were sequentially extracted with acetone and water, and extracts were analyzed for their toxicity in cell lines with key roles in the skin context (HaCAT, 3T3L1, and hCMEC). The non-toxic extracts were chemically characterized in terms of proteins, carotenoids, phenols, and chlorophyll a, and their anti-aging potential was explored through their ability to scavenge the physiological free radical superoxide anion radical (O2•−), to reduce the activity of the MMPs elastase and hyaluronidase, to inhibit tyrosinase and thus avoid melanin production, and to block UV-B radiation (sun protection factor, SPF). Leptolyngbya species stood out for anti-aging purposes: L. boryana LEGE 15486 presented a remarkable SPF of 19 (at 200 µg/mL), being among the best species regarding O2•− scavenging, (IC50 = 99.50 µg/mL) and also being able to inhibit tyrosinase (IC25 = 784 µg/mL), proving to be promising against UV-induced skin-aging; L. ectocarpi LEGE 11479 was more efficient in inhibiting MMPs (hyaluronidase, IC50 = 863 µg/mL; elastase, IC50 = 391 µg/mL), thus being the choice to retard dermal density loss. Principal component analysis (PCA) of the data allowed the grouping of extracts into three groups, according to their chemical composition; the correlation of carotenoids and chlorophyll a with MMPs activity (p < 0.01), O2•− scavenging with phenolic compounds (p < 0.01), and phycocyanin and allophycocyanin with SPF, pointing to these compounds in particular as responsible for UV-B blockage. This original survey explores, for the first time, the biotechnological potential of these cyanobacteria strains in the field of skin aging, demonstrating the promising, innovative, and multifactorial nature of these microorganisms.

Radioprotective Effect of Nigella Sativa Oil on Heart Tissues of Rats Exposed to Irradition

Abstract Background Various studies are ongoing related to the radioprotective agents. Herbal preparations are currently becoming popular because of their beneficial effects with fewer side effects compared to the synthetic/semi-synthetic medicines, and Nigella sativa oil (NSO) is only one of them. Objective To investigate NSO for its antioxidant effects on the heart tissue of rats exposed to ionizing radiation (IR). Methods Thirty six male albino Wistar rats, divided into four groups, were designated to group I (IR plus NSO group) that received both 5 Gray of gamma IR to total cranium and NSO; group II (IR alone group) that received IR plus saline, group III (control group of NSO) that received saline and did not receive NSO or IR; group IV (control group) that received only sham IR. Alterations in Total antioxidant status (TAS) and Total oxidant status (TOS), Oxidative stres index (OSI), Sulhydryl group (SH), Lipid hydroperoxide (LOOH), Paraoxonase (PON) levels, Arylesterase (ARE) and Ceruloplasmin (CER) activities in homogenized heart tissue of rats were measured by biochemical methods. Results In heart tissue of the rats in the IR alone group (group II) LOOH, TOS and OSI levels were found to be higher, ARE activity and TAS level were found to be lower than all of the other groups (p < 0.01). These results also support that IR increases oxidative stress and NSO's protective effect. Conclusion NSO would reduce the oxidative damage in the irradiated heart tissue in the experimental rat model.

A collagen extraction and deuterium oxide stable isotope tracer method for the quantification of bone collagen synthesis rates in vivo.

The development of safe and practical strategies to prevent weakening of bone tissue is vital, yet attempts to achieve this have been hindered by a lack of understanding of the short-term (days-weeks) physiology of bone collagen turnover. To address this, we have developed a method to quantify bone collagen synthesis in vivo, using deuterium oxide (D2 O) tracer incorporation techniques combined with gas chromatography pyrolysis isotope-ratio mass spectrometry (GC-pyrolysis-IRMS). Forty-six male and female rats from a selectively bred model ingested D2 O for 3 weeks. Femur diaphyses (FEM), tibia proximal (T-PRO), and distal (T-DIS) epiphyses-metaphyses and tibia mid-shaft diaphyses (T-MID) were obtained from all rats after necropsy. After demineralisation, collagen proteins were isolated and hydrolysed and collagen fractional synthetic rates (FSRs) determined by incorporation of deuterium into protein-bound alanine via GC-pyrolysis-IRMS. The collagen FSR for the FEM (0.131 ± 0.078%/day; 95% CI [0.106-0.156]) was greater than the FSR at T-MID (0.055 ± 0.049%/day; 95% CI [0.040-0.070]; p < 0.001). The T-PRO site had the highest FSR (0.203 ± 0.123%/day; 95% CI [0.166-0.241]) and T-DIS the lowest (0.027 ± 0.015%/day; 95% CI [0.022-0.031]). The three tibial sites exhibited different FSRs (p < 0.001). Herein, we have developed a sensitive method to quantify in vivo bone collagen synthesis and identified site-specific rates of synthesis, which could be applicable to studies of human bone collagen turnover.

Evaluation of a method for measuring the radioprotective metabolite WR-1065 in plasma using chemical derivatization combined with UHPLC-MS/MS.

Hypotension is the dose-limiting side effect of the radio-protective drug Amifostine and results from relaxation of the vascular smooth muscle, which is directly mediated by the active metabolite, WR-1065, of Amifostine. The route of administration (currently FDA-approved only for intravenous administration) and the rapid metabolic conversion of Amifostine combine to yield high systemic levels of WR-1065 and facilitate the onset of hypotension. Research efforts aiming to optimize the delivery of WR-1065 to maintain efficacy while reducing its peak, systemic concentration below levels that induce hypotension are underway. To fully characterize the effect of reduced dose levels and alternative routes of administration of Amifostine on systemic WR-1065 concentrations, improved analytical techniques are needed. We have developed and evaluated a highly sensitive method for measuring WR-1065 in rat plasma that employs chemical derivatization, protein precipitation and UPLC-MS/MS analysis. The method exhibits a limit of quantification (LOQ) of 7.4 nM in plasma, which is a significant improvement over conventional approaches that utilize LC-electrochemical detection (ECD) (LOQ 150 nM or higher). The method was assessed in a pharmacokinetics study in rats administered Amifostine intravenously and via direct jejunal injection (10 mg/kg each route). The bioavailability of WR-1065 was 61.5% after direct jejunal injection indicating rapid conversion and absorption of the metabolite in the intestinal tract. This demonstrates that an oral formulation of Amifostine designed for site-specific release of the drug in the upper GI tract can deliver systemic absorption/conversion to WR-1065, provided that the formulation protects the therapeutic from gastric decomposition in the stomach.

The potential roles of bacteria to improve radiation treatment outcome

Many combined therapies have been proposed to enhance radiotherapy outcome, but they have several limitations. As a new feasible strategy, combination of radiotherapy with bacteria showed a significant positive impact on the tumor treatment and metastasis inhibition. Although probiotic bacteria and radiotherapy alone can be effective in the treatment of different cancers, the combination of these two therapies seems to enhance therapeutic outcome and is cost-effective. Bacterial cells can act as therapeutic/gene/drug delivery vehicles as well as theranostic agents. In this communication, we reviewed current evidences, studies, suggestions, and future-based directions on combination of radiotherapy and bacteria. In another sections, an overview on tumor hypoxia, bacteria in cancer therapy, and combination of radiotherapy and bacteria is presented. A brief overview on trials and animal studies which used bacteria to protect normal tissues against radiotherapy-induced complications is also included (AU)

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The SOS Chromotest applied for screening plant antigenotoxic agents against ultraviolet radiation.

In this work, we investigated the usefulness of the SOS Chromotest for screening plant antigenotoxic agents against ultraviolet radiation (UV). Fifty Colombian plant extracts obtained by supercritical fluid (CO2) extraction, twelve plant extract constituents (apigenin, carvacrol, ß-caryophyllene, 1,8-cineole, citral, p-cymene, geraniol, naringenin, pinocembrin, quercetin, squalene, and thymol) and five standard antioxidant and/or photoprotective agents (curcumin, epigallocatechin gallate, resveratrol, α-tocopherol, and Trolox®) were evaluated for their genotoxicity and antigenotoxicity against UV using the SOS Chromotest. None of the plant extracts, constituents or agents were genotoxic in the SOS Chromotest at tested concentrations. Based on the minimal extract concentration that significantly inhibited UV-genotoxicity (CIG), five plant extracts were antigenotoxic against UV as follows: Baccharis nítida (16 µg mL-1) = Solanum crotonifolium (16 µg mL-1) > Hyptis suaveolens (31 µg mL-1) = Persea caerulea (31 µg mL-1) > Lippia origanoides (62 µg mL-1). Based on CIG values, the flavonoid compounds showed the highest antigenotoxic potential as follows: apigenin (7 µM) > pinocembrin (15 µM) > quercetin (26 µM) > naringenin (38 µM) > epigallocatechin gallate (108 µM) > resveratrol (642 µM). UV-genotoxicity inhibition with epigallocatechin gallate, naringenin and resveratrol was related to its capability for inhibiting protein synthesis. A correlation analysis between compound antigenotoxicity estimates and antioxidant activity evaluated by the oxygen radical absorbance capacity (ORAC) assay showed that these activities were not related. The usefulness of the SOS Chromotest for bioprospecting of plant antigenotoxic agents against UV was discussed.

In vitro screening of radioprotective properties in the novel glucosylated flavonoids.

Novel glucosyl flavonoids are developed by the addition of glucose to naturally occurring flavonoids. Flavonoids are known antioxidants that possess radioprotective properties. In order to investigate the radioprotective properties of novel glucosyl flavonoids, in vitro DNA double-strand breaks (DSBs) analysis was carried out. In the present study, Quercetin, Naringenin, and Hesperetin groups of flavonoids included in the natural and novel glucosyl 13 flavonoids were investigated. Flavonoids were mixed with Lambda DNA, and subsequently exposed to gamma­rays. Furthermore, DNA DSB yields were visualized by gel electrophoresis. Quercetin derivatives displayed reduced DNA DSB formation at 10 µM. At a high concentration, the majority of flavonoids displayed radioprotective properties as a reduction of DSB yields. Suppression of DSB formation was confirmed via the molecular combing assay for Quercetin, and three monoglucosyl flavonoids. Glucosylation showed positive effects for radioprotection and monoglucosyl-Rutin showed superior radioprotective properties when compared to monoglucosyl-Naringin and Hesperidin. In addition, Quercetin derivatives had greater total antioxidant capacities and DPPH radical scavenging ability than other flavonoid groups. Since Quercetin, Isoquercetin, and Rutin display poor water solubility, monoglucosyl-Rutin, maltooligosyl-Isoquercetin, and maltooligosyl-Rutin may be better radioprotective agents and easily bioavailable with increased water solubility.

Radioprotective properties of sodium humate in radiation-induced mutagenesis in cultured lymphocytes of thyroid cancer patients.

UNLABELLED: To investigate the effect of sodium humate on the level of cytogenetic damage in culture of lymphocytes of patients with thyroid cancer after γ-irradiation. MATERIALS AND METHODS: Metaphase analysis of chromosome aberrations in cultured peripheral blood lymphocytes of 10 individuals with thyroid cancer was performed after irradiation of lymphocytes in vitro at a dose of 1 Gy from (137)Cs source at the early G0 phase of cell cycle. Sodium humate was added to cell culture for 30 ± 15 min after phytohemagglutinin stimulation at concentrations of 10 and 100 µg/ml. RESULTS: Sodium humate exhibited antimutagenic properties. The preparation at a concentration of 10 µg/ml was more effective than at a concentration of 100 µg/ml, reducing the average incidence of radiation-induced chromosome aberrations by 51.88 and 38.77%, respectively. The most pronounced antimutagenic effect of sodium humate was the reduction of the frequency of chromosomal type aberrations, however, such efficiency varied between individual patients with thyroid cancer. CONCLUSIONS: Sodium humate could be considered as a potential therapeutic modifier of radiation damage.

In situ growth and phenyl functionalization of titania nanoparticles coating for solid-phase microextraction of ultraviolet filters in environmental water samples followed by high performance liquid chromatography-UV detection.

Based on TiO2-nanoparticles coating fabricated by a one-step anodization method on titanium wire substrate, a novel phenyl functionalized solid-phase microextraction (SPME) fiber coating was prepared by simple and rapid in situ chemical assembling technique between the fiber surface titanol groups and trichlorophenylsilane reaction. The as-fabricated fiber exhibited good extraction capability for some UV filters and was employed to determine the ultraviolet (UV) filters in combination with high performance liquid chromatography-UV detection (HPLC-UV). The main parameters affecting extraction performance were investigated and optimized. Under the optimized conditions, the developed method was applied to detect several UV filters at trace concentration levels with only 8 mL of sample volume. They were determined in the range from 0.005 to 25 µg L(-1) with detection limits (S/N=3) from 0.1 to 50 ng L(-1). The relative standard deviations (RSDs) for single fiber repeatability varied from 4.6 to 6.5% (n=5) and fiber-to-fiber reproducibility (n=5) ranged from 5.5 to 9.1%. The linear ranges spanned two-four magnitudes with correlation coefficients above 0.9990. Five real water samples including four Yellow River water samples and one rain water sample were determined sensitively with good recoveries ranging from 86.2 to 105.5%. The functionalized fiber coating performed good reproducible manner, high mechanical strength, good stability and long service life. Moreover, this study proposed an efficient sample pretreatment method for the determination of UV filters from environmental water samples.

Natural UV-protective organic matter in thermal water.

Medical significance of the organic fractions of natural waters is still poorly understood. Nevertheless, there are putative biologically active organic compounds found in natural medical waters and related clay or mud samples. Organic fractions of five thermal (spa) water samples of different geochemical origin were tested for photo-biological effects. To study possible effects on the UV sensitivity of Salmonella typhimurium TA strains, the organic isolates were applied in the "plate incorporation" Ames test combined with UV-irradiation. Four samples showed measurable survival of TA100 his+ revertants following exposure to a normally lethal UV dose. Metabolic activation with a mammalian microsomal fraction (S9) elevated the effect detected (up to 61% survival). This is the first study to demonstrate the UV-protective property of organic matter in natural thermal water samples used in balneotherapy.

The high-energy radiation protectant extracellular sheath pigment scytonemin and its reduced counterpart in the cyanobacterium Scytonema sp. R77DM.

A cyanobacterial extracellular sheath pigment from Scytonema sp. R77DM was partially characterized and investigated for its increased production under abiotic factors, and UV-screening function. HPLC with PDA detection, and ion trap liquid chromatography/mass spectrometry analysis revealed the presence of a pigment scytonemin and its reduced counterpart. Ultraviolet radiation showed more stimulative effects on scytonemin production. A significant synergistic enhancement of scytonemin synthesis was observed under combined stress of heat and UV radiation. Scytonemin also exhibited efficient UV-screening function by reducing the in vivo production of reactive oxygen species (ROS) and cyclobutane thymine dimer. UV-induced formation of ROS and thymine dimer was also reduced upon exposure of cyanobacterial cells to exogenous antioxidant, ascorbic acid; however, the effect was more significant when both scytonemin and ascorbic acid were applied in combination. Moreover, the results indicate the potential role of scytonemin pigment as natural photoprotectant against high energy solar insolation.

Quantitative analysis of hindered amine light stabilizers by CZE with UV detection and quadrupole TOF mass spectrometric detection.

The current work describes the development of a CZE method with quadrupole QTOF-MS detection and UV detection for the quantitation of Cyasorb 3529, a common hindered amine light stabilizer (HALS), in polymer materials. Analysis of real polymer samples revealed that the oligomer composition of Cyasorb 3529 changes during processing, a fact hampering the development of a straightforward method for quantitation based on calibration with a Cyasorb 3529 standard. To overcome this obstacle in-depth investigations of the oligomer composition of this HALS using QTOF-MS and QTOF-MS/MS had to be performed whereby 22 new oligomer structures, in addition to the ten structures already described, were identified. Finally, a CZE method for quantitative analysis of this HALS was developed starting with a comprehensive characterization of a Cyasorb 3529 standard using CZE-QTOF-MS, subsequently allowing the correct assignment of most Cyasorb 3529 oligomers in an electropherogram with UV detection. Employing the latter detection technique and hexamethyl-melamine as internal standard, peak areas obtained for the melamine could be correlated with those from the triazine ring, the UV-absorbing unit present in the HALS. This approach finally allowed proper quantitation of the single oligomers of Cyasorb 3529, an imperative for the quantitative assessment of this HALS in real polymer samples.

Analysis of UV-absorbing photoprotectant mycosporine-like amino acid (MAA) in the cyanobacterium Arthrospira sp. CU2556.

Mycosporine-like amino acids (MAAs) are ecologically important biomolecules with great photoprotective potential. The present study aimed to investigate the biosynthesis of MAAs in the cyanobacterium Arthrospira sp. CU2556. High-performance liquid chromatography (HPLC) with photodiode-array detection studies revealed the presence of a UV-absorbing compound with an absorption maximum at 310 nm. Based on its UV absorption spectrum and ion trap liquid chromatography/mass spectrometry (LC/MS) analysis, the compound was identified as a primary MAA mycosporine-glycine (m/z: 246). To the best of our knowledge this is the first report on the occurrence of MAA mycosporine-glycine (M-Gly) in Arthrospira strains studied so far. In contrast to photosynthetic activity under UV-A radiation, the induction of the biosynthesis of M-Gly was significantly more prominent under UV-B radiation. The content of M-Gly was found to increase with the increase in exposure time under UV-B radiation. The MAA M-Gly was highly stable under UV radiation, heat, strongly acidic and alkaline conditions. It also exhibited good antioxidant activity and photoprotective ability by detoxifying the in vivo reactive oxygen species (ROS) generated by UV radiation. Our results indicate that the studied cyanobacterium may protect itself by synthesizing the UV-absorbing/screening compounds as important defense mechanisms, in their natural brightly-lit habitat with high solar UV-B fluxes.

Synthesis of analogs of the radiation mitigator JP4-039 and visualization of BODIPY derivatives in mitochondria.

JP4-039 is a lead structure in a series of nitroxide conjugates that are capable of accumulating in mitochondria and scavenging reactive oxygen species (ROS). To explore structure-activity relationships (SAR), new analogs with variable nitroxide moieties were prepared. Furthermore, fluorophore-tagged analogs were synthesized and provided the opportunity for visualization in mitochondria. All analogs were tested for radioprotective and radiomitigative effects in 32Dcl3 cells.

Mechanism of radioprotection by δ-tocotrienol: pharmacokinetics, pharmacodynamics and modulation of signalling pathways.

OBJECTIVE: The objective of this study was to investigate the correlation between in vivo δ-tocotrienol (DT3) pharmacokinetics, pharmacodynamics and radiation protection, and to evaluate the effect of DT3 pre-treatment on radiation-induced alterations in apoptotic and autophagic pathways. METHODS: We evaluated pharmacokinetics (plasma, 0.5 to 12 h) and pharmacodynamics (peripheral blood indices; day 3, 7, 10 and 14) after a single subcutaneous injection of 300 mg kg(-1) DT3 in unirradiated CD2F1 mice. Next, we monitored 30-day post-irradiation survival (9.25 Gy) and haematopoietic recovery of DT3-treated mice (7 Gy) exposed to cobalt-60 γ-irradiation. The effects of DT3 on irradiated bone marrow apoptosis and autophagy were determined by analyses of key caspases (3, 7, 9 and 8), beclin-1 and light chain 3 conversion. RESULTS: Plasma concentration of DT3 reached ∼195 µM (Cmax) 1 h after injection (Tmax), and DT3 was eliminated from plasma 12 h later. In unirradiated mice, DT3 significantly increased white blood cells (WBCs), neutrophils, lymphocytes (day 3 post DT3 injection) and platelets (day 7) by 1.5- to 2-fold, over vehicle-treated control. DT3 pre-treatment improved 30-day survival to 100% (∼15% in control) and accelerated recovery of reticulocytes, platelets, WBCs, neutrophils, lymphocytes and monocytes in peripheral blood. DT3 reduced activation of caspase-8, caspase-3 and caspase-7, inherent to apoptosis, while increasing autophagy-related beclin-1 expression in irradiated bone marrow. CONCLUSION: These data indicate that DT3 stimulates multilineage haematopoiesis, protects against radiation-induced apoptosis downstream of the mitochondria and stimulates cytoprotective autophagy. Apart from a potent antioxidant activity, DT3 may elicit survival advantage following irradiation by enhancing haematopoiesis and modulating signalling pathways.

Medidas de radioprotección empleadas por alumnos de odontología / Radiation protection measures used by dental students

A raíz del descubrimiento de la radiactividad y los rayos X finales del siglo XIX, se pusieron de manifiesto los daños producidos por las radiaciones ionizantes. El uso de dos técnicas adecuadas para la protección del operador reduce a un mínimo la dosis de radiación que recibe el radiólogo. La cantidad de radiación X utilizada en la radiografía dental es pequeña, pero causa daños biológicos. La exposición a los rayos X se inicia al cursar la materia de radiología y puede persistir durante toda la vida profesional del odontólogo. Con el objetivo de conocer cuáles son las medidas empleadas por los alumnos de odontología se realizó un estudio observacional descriptivo de corte transverso en 10 alumnos del cuarto curso de la Facultad de Odontología de la Universidad Nacional de Asunción en el cual mediante un cuestionario se observó que el 100% no utiliza delantal de plomo, la clínica en la cual trabajan no posee paredes de plomo y no cumple con la distancia mínima de exposición a la hora de realizar las tomas radiográficas. Cumplen con las medidas recomendadas al utilizar placas rápidas (E) y no sujetarlas. Las dosis absorbidas por los alumnos medidas con dosímetros personales TLD (Dosimetría Termoluminiscente) dieron un resultado menor al límite de detección 0,1 mSv/mes

Development of an LC-MS/MS assay to determine plasma pharmacokinetics of the radioprotectant octadecenyl thiophosphate (OTP) in monkeys.

Octadecenyl thiophosphate (OTP), a synthetic analogue of the lysophospholipid growth factor lysophosphatidic acid (LPA), significantly reduces mortality following a lethal dose of LD(80/30) radiation exposure in a mouse model of whole-body irradiation. To facilitate dose scaling between species, we developed a novel liquid chromatography/tandem mass spectrometry (LC-MS/MS) for the preclinical pharmacokinetic characterization of OTP in monkeys. Sample extraction was carried out using a butanol based liquid-liquid extraction method. A partially deuterated OTP analogue was used as internal standard (IS). OTP and IS were separated by reversed-phase liquid chromatography on a C-8 column using 10mM ammonium acetate and acetonitrile. A triple quadrupole mass spectrometer operating in the negative electrospray ionization mode with multiple reaction monitoring was used to detect OTP and IS transitions of m/z 363.1-->95.0 and 403.1-->95.0. The method was applied to determine pharmacokinetic parameters in monkeys receiving a single oral OTP dose (3mg/kg). OTP is readily absorbed with a relatively long half-life which supports further preclinical testing of OTP as a radioprotectant in monkeys.

Combined effects of UVR and temperature on the survival of crab larvae (Zoea I) from Patagonia: the role of uv-absorbing compounds.

The aim of our study was to assess the combined impact of UVR (280-400 nm) and temperature on the first larval stage (Zoea I) of three crab species from the Patagonian coast: Cyrtograpsus altimanus, C. angulatus, and Leucippa pentagona. We determined the survival response of newly hatched Zoea I after being exposed for 8-10 h under a solar simulator (Hönle SOL 1200) at 15 and 20 degrees C. There was no mortality due to Photosynthetic Active Radiation (PAR, 400-700 nm) or ultraviolet-A radiation (UV-A, 315-400 nm), and all the observed mortality was due to ultraviolet-B radiation (UV-B, 280-315 nm). The data of larval mortality relative to exposure time was best fit using a sigmoid curve. Based on this curve, a threshold (Th) and the lethal dose for 50% mortality (LD(50)) were determined for each species. Based on the Th and LD(50), C. altimanus was found to be the most resistant species, while L. pentagona was found to be the most sensitive to UV-B. For both species of Cyrtograpsus, mortality was significantly lower at 20 degrees C than at 15 degrees C; however, no significant differences between the two temperature treatments were found in L. pentagona. Bioaccumulation of UV-absorbing compounds in the gonads and larvae of C. altimanus, and to a lesser extent in C. angulatus, might have contributed for counteracting the impact of UV-B. However, most of the resilience to UV-B observed with the increase in temperature might be due to an increase in metabolic activity caused by a repair mechanism mediated by enzymes.

Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation.

While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome.

Protective effect of Calendula officinalis extract against UVB-induced oxidative stress in skin: evaluation of reduced glutathione levels and matrix metalloproteinase secretion.

BACKGROUND AND PURPOSE: Calendula officinalis flowers have long been employed time in folk therapy, and more than 35 properties have been attributed to decoctions and tinctures from the flowers. The main uses are as remedies for burns (including sunburns), bruises and cutaneous and internal inflammatory diseases of several origins. The recommended doses are a function both of the type and severity of the condition to be treated and the individual condition of each patient. Therefore, the present study investigated the potential use of Calendula officinalis extract to prevent UV irradiation-induced oxidative stress in skin. METHODS: Firstly, the physico-chemical composition of marigold extract (ME) (hydroalcoholic extract) was assessed and the in vitro antioxidant efficacy was determined using different methodologies. Secondly, the cytotoxicity was evaluated in L929 and HepG2 cells with the MTT assay. Finally, the in vivo protective effect of ME against UVB-induced oxidative stress in the skin of hairless mice was evaluated by determining reduced glutathione (GSH) levels and monitoring the secretion/activity of metalloproteinases. RESULTS AND CONCLUSIONS: The polyphenol, flavonoid, rutin and narcissin contents found in ME were 28.6 mg/g, 18.8 mg/g, 1.6 mg/g and 12.2mg/g, respectively and evaluation of the in vitro antioxidant activity demonstrated a dose-dependent effect of ME against different radicals. Cytoxicity experiments demonstrated that ME was not cytotoxic for L929 and HepG2 cells at concentrations less than or equal to of 15 mg/mL. However, concentrations greater than or equal to 30 mg/mL, toxic effects were observed. Finally, oral treatment of hairless mice with 150 and 300 mg/kg of ME maintained GSH levels close to non-irradiated control mice. In addition, this extract affects the activity/secretion of matrix metalloproteinases 2 and 9 (MMP-2 and -9) stimulated by exposure to UVB irradiation. However, additional studies are required to have a complete understanding of the protective effects of ME for skin.