Protective effect of Chromobacterium violaceum and violacein against bone resorption by periodontitis.

OBJECTIVES: The aim of this study was to evaluate the potential protective effect of Chromobacterium violaceum and violacein against periodontitis, in experimental models. MATERIALS AND METHODS: A double-blind experimental study on the exposure to C. violaceum or violacein in experimentally ligature-induced periodontitis, as preventive factors against alveolar bone loss by periodontitis. Bone resorption was assessed by morphometry. Antibacterial potential of violacein was assessed in an in vitro assay. Its cytotoxicity and genotoxicity were evaluated using the Ames test and SOS Chromotest assay, respectively. RESULTS: The potential of C. violaceum to prevent/limit bone resorption by periodontitis was confirmed. Daily exposure to 106 cells/ml in water intake since birth and only during the first 30 days of life significantly reduced bone loss from periodontitis in teeth with ligature. Violacein extracted from C. violaceum was efficient in inhibiting or limiting bone resorption and had a bactericidal effect against Porphyromonas gingivalis in the in vitro assay. CONCLUSIONS: We conclude that C. violaceum and violacein have the potential to prevent or limit the progression of periodontal diseases, in an experimental model. CLINICAL RELEVANCE: The effect of an environmental microorganism with potential action against bone loss in animal models with ligature-induced periodontitis represents the possibility of understanding the etiopathogenesis of periodontal diseases in populations exposed to C. violaceum and the possibility of new probiotics and antimicrobials. This would imply new preventive and therapeutic possibilities.

Cytotoxicity of Extracts from Petiveria alliacea Leaves on Yeast.

Petiveria alliacea L. is a plant used in traditional medicine harboring pharmacological properties with anti-inflammatory, antinociceptive, hypoglycemiant and anesthetic activities. This study assessed the potential cytotoxic, genotoxic and mutagenic effects of ethanolic extract of P. alliacea on Saccharomyces cerevisiae strains. S. cerevisiae FF18733 (wild type) and CD138 (ogg1) strains were exposed to fractioned ethanolic extracts of P. alliacea in different concentrations. Three experimental assays were performed: cellular inactivation, mutagenesis (canavanine resistance system) and loss of mitochondrial function (petites colonies). The chemical analyses revealed a rich extract with phenolic compounds such as protocatechuic acid, cinnamic and catechin epicatechin. A decreased cell viability in wild-type and ogg1 strains was demonstrated. All fractions of the extract exerted a mutagenic effect on the ogg1 strain. Only ethyl acetate and n-butanol fractions increased the rate of petites colonies in the ogg1 strain, but not in the wild-type strain. The results indicate that fractions of mid-polarity of the ethanolic extract, at the studied concentrations, can induce mutagenicity mediated by oxidative lesions in the mitochondrial and genomic genomes of the ogg1-deficient S. cerevisiae strain. These findings indicate that the lesions caused by the fractions of P. alliacea ethanolic extract can be mediated by reactive oxygen species and can reach multiple molecular targets to exert their toxicity.

The stochastic θ -SEIHRD model: Adding randomness to the COVID-19 spread.

In this article we mainly extend a newly introduced deterministic model for the COVID-19 disease to a stochastic setting. More precisely, we incorporated randomness in some coefficients by assuming that they follow a prescribed stochastic dynamics. In this way, the model variables are now represented by stochastic process, that can be simulated by appropriately solving the system of stochastic differential equations. Thus, the model becomes more complete and flexible than the deterministic analogous, as it incorporates additional uncertainties which are present in more realistic situations. In particular, confidence intervals for the main variables and worst case scenarios can be computed.

Nuclear and mitochondrial genome instability induced by fractions of ethanolic extract from Hovenia dulcis Thunberg in Saccharomyces cerevisiae strains.

Hovenia dulcis is a plant commonly used as a pharmaceutical supplement, having displayed important pharmacological properties such antigiardic, antineoplastic and hepatoprotective. The purpose of this work was investigate the cytotoxic, genotoxic and mutagenic potential from fractions of Hovenia dulcis ethanolic extract on Saccharomyces cerevisiae strains FF18733 (wild type) and CD138 (ogg1). Ethanolic extract from Hovenia dulcis leaves was fractioned using organic solvents according to increasing polarity: Hexane (1:1), dichlorometane (1:1), ethyl acetate (1:1) and butanol (1:1). Three experimental assays were performed, such as (i) inactivation of cultures; (ii) mutagenesis (canavanine resistance system) and (iii) loss of mitochondrial function (petites colonies). The findings shown a decrease in cell viability in FF18733 and CD138 strains; all fractions of the extract were mutagenic in CD138 strain; only ethyl acetate and butanol fractions increased the rate of petites colonies for CD138 strains. Ethyl acetate and n-butanol fractions induces mutagenicity, at the evaluated concentrations, in mitochondrial and genomic DNA in CD138 strain, mediated by oxidative lesions. In conclusion, it is possible to infer that the lesions caused by the extract fractions could be mediated by reactive oxygen species and might reach multiple molecular targets to cause cellular damage.

Insights and controversies on sunscreen safety.

Although sunlight provides several benefits, ultraviolet (UV) radiation plays an important role in the development of various skin damages such as erythema, photoaging, and photocarcinogenesis. Despite cells having endogenous defense systems, damaged DNA may not be efficiently repaired at chronic exposure. In this sense, it is necessary to use artificial defense strategies such as sunscreen formulations. UV filters should scatter, reflect, or absorb solar UV radiation in order to prevent direct or indirect DNA lesions. However, the safety of UV filters is a matter of concern due to several controversies reported in literature, such as endocrine alterations, allergies, increased oxidative stress, phototoxic events, among others. Despite these controversies, the way in which sunscreens are tested is essential to ensure safety. Sunscreen regulation includes mandatory test for phototoxicity, but photogenotoxicity testing is not recommended as a part of the standard photosafety testing program. Although available photobiological tests are still the first approach to assess photosafety, they are limited. Some existing tests do not always provide reliable results, mainly due to limitations regarding the nature of the assessed phototoxic effect, cell UV sensitivity, and the irradiation protocols. These aspects bring queries regarding the safety of sunscreen wide use and suggest the demand for the development of robust and efficient in vitro screening tests to overcome the existing limitations. In this way, Saccharomyces cerevisiae has stood out as a promising model to fill the gaps in photobiology and to complete the mandatory tests enabling a more extensive and robust photosafety assessment.

Saccharomyces cerevisiae strains as bioindicators for titanium dioxide sunscreen photoprotective and photomutagenic assessment.

Although several short-term assays are available for cosmetic photosafety assessment, cell models are usually highly sensitive to UV radiation, tending to overestimate both phototoxic and photomutagenic risks. In addition, these assays are performed with UV doses/fluences that do not correspond to actual environmental conditions. In this sense, Saccharomyces cerevisiae has already proved to be an interesting tool to predict photomutagenic potential of several compounds, including sunscreens. Yeast can support environmental UVB doses compatible with human daily sunlight exposure, allowing the use of irradiation sources to faithfully mimic the external conditions of ambient sunlight. Herein, we used a set of S. cerevisiae mutant strains sensitive to UVA, UVB and Solar Simulated Light sources in order to evaluate their potential as bioindicators for sunscreen development. The bioindicator potential of the strains was tested with the widely-used titanium dioxide inorganic sunscreen. The AWP001 (yno1) and LPW002 (ogg1yno1) strains obtained in this study stood out as promising experimental tools for the validation of this assay. Overall, our results evidenced a set of S. cerevisiae strains particularly useful for evaluating both photoprotective (efficacy) and photo/antiphotomutagenic (safety) potential of UV filters, meeting the industries and regulatory agencies demand for robust and efficient in vitro screening tests.

Photoprotection assessment of olive (Olea europaea L.) leaves extract standardized to oleuropein: In vitro and in silico approach for improved sunscreens.

Olive leaves contain higher amount of polyphenols than olive oil and represent a waste product from olive harvest and pruning of olive trees. The most abundant compound in olive leaves is oleuropein. Benefits of the topical application of olive leaves extract were previously reported, but little information is available on its photoprotective potential and the result of the association of this extract with organic UV filters in topical sunscreen formulations. The olive leaves extract photoprotective potential is less explored for both oral and topical photoprotection in comparison with other plants extracts and polyphenols, such as Polypodium leucotomos extract and resveratrol. There are increasing efforts towards developing more efficient sunscreens and a photoprotection assessement along with a better understanding of the photochemistry of naturally occurring sunscreens could aid the design of new and improved commercial sunscreen formulations. This study was designed to investigate the photoprotective potential of olive leaves extract standardized for oleuropein performing a set of in vitro and in silico tools as an innovative approach, highlighting yeast assays, in vitro Sun Protection Factor (SPF) and molecular modelling studies of UV absorption. This study supports the use of olive leaves extract for photoprotection, as an effective photoprotective, anti-mutagenic and antioxidant active, also showing a synergistic effect in association with UV filters with an improvement on in vitro SPF of sunscreen formulations.

Microbiological Decontamination of Water: Improving the Solar Disinfection Technique (SODIS) with the Use of Nontoxic Vital Dye Methylene Blue.

Rational use of water is a major challenge for governments and global organizations, with easy and inexpensive interventions being sought by communities that are not supplied with drinking water. In this context, solar disinfection (SODIS) has shown great efficiency for water disinfection. To speed up the process and improve inactivation, we studied the effects of methylene blue (MB) as a photodynamic agent because of its ability to absorb visible light (red wavelength) and generate singlet oxygen as a reactive species, thereby inactivating bacteria and viruses present in water. In this study, samples of clean mineral water were artificially contaminated with Gram-positive (Staphylococcus epidermidis or Deinococcus radiodurans) or with Gram-negative strains (Escherichia coli or Salmonella typhimurium) and exposed to traditional SODIS or to MB-SODIS. A lethal synergistic effect was observed when cultures were illuminated in the presence of MB. The obtained results indicate that bacterial inactivation can be achieved in a much shorter time when using MB associated with SODIS treatment. Therefore, this technique was able to provide safe water for consumption through the inactivation of microorganisms in general, including pathogens and some strains resistant to the traditional SODIS procedure, thus allowing its use in areas usually less exposed to sunlight.

Impact of violacein from Chromobacterium violaceum on the mammalian gut microbiome.

Violacein is a violet pigment produced by Chromobacterium violaceum that possesses several functions such as antibacterial, antiviral, antifungal, and antioxidant activities. The search for potential compounds and therapies that may interfere with and modulate the gut microbial consortia without causing severe damage and increased resistance is important for the treatment of inflammatory, allergic, and metabolic diseases. The aim of the present work was to evaluate the ability of violacein to change microbial patterns in the mammalian gut by favoring certain groups over the others in order to be used as a therapy for diseases associated with changes in the intestinal microflora. To do this, we used male Wistar rats, and administered violacein orally, in low (50 µg/ml) and high (500 µg/ml) doses for a month. Initially, the changes in the microbial diversity were observed by DGGE analyses that showed that the violacein significantly affects the gut microbiota of the rats. Pyrosequencing of 16S rDNA was then employed using a 454 GS Titanium platform, and the results demonstrated that higher taxonomic richness was observed with the low violacein treatment group, followed by the control group and high violacein treatment group. Modulation of the microbiota at the class level was observed in the low violacein dose, where Bacilli and Clostridia (Firmicutes) were found as dominant. For the high violacein dose, Bacilli followed by Clostridia and Actinobacteria were present as the major components. Further analyses are crucial for a better understanding of how violacein affects the gut microbiome and whether this change would be beneficial to the host, providing a framework for the development of alternative treatment strategies for intestinal diseases using this compound.

Effect of the FE2+ chelation by 2,2'-dipyridyl in the doxorubicin-induced lethality in breast tumor cell lines.

Breast cancer cells may exhibit changes in iron homeostasis, which results in increased labile iron pool (LIP) levels. Several studies highlight the crucial role of high LIP levels in the maintenance of tumor cell physiology. Iron chelators have been tested in anticancer therapy in combination with chemotherapeutic agents, to improve drug efficacy. Thus, the aim of this study was to evaluate the effect of 2,2'-dipyridyl (DIP), a Fe2+ chelator, in combination with doxorubicin (DOX) in breast tumor cells. The maximum concentration of DIP that did not significantly reduce the viability of MDA-MB-231 cells was 10µM and for MCF-7 cells was 50µM. We observed that MCF-7 had higher LIP levels than MDA-MB-231 cells. DIP alone increased ROS generation in MCF-7 cells, and DIP pretreatment reduced ROS generation induced by DOX treatment. In conclusion, the increase in MCF-7 cell viability induced by DIP pretreatment in DOX-treated cells seems to be related to an increase in the cellular antioxidant capacity and the iron chelator did not improve drug efficacy in the two breast tumor cell lines analyzed.

Histological observation of hairless mice skin after exposure to Simulated Solar Light: Comparison between the histological findings with different methodologies and 3R principle correlations.

BACKGROUND: Albino hairless mouse (AHM) has been used as a biological model in photodermatology. However, the experimental landscape is diverse to follow and need particular attention. PURPOSE: Irradiation parameters were investigated for the development of a protocol to assess alterations in the AHM skin using Simulated Solar Light (SSL). The present study was compared with published articles (last 15 years) according to irradiation protocols, morphological findings to minimize animal suffering and UV exposure. MATERIALS AND METHODS: Three groups: Control (G1), experimental - sunburn (G2) and skin photodamage assay (G3). G2 were immobilized and exposed to SSL once for 15, 30 and 45min. G3 were exposed to SSL, without immobilization, for 15min once a day for one week. The dorsal skin was analyzed using hematoxylin and eosin technique. RESULTS: G2 displayed different sunburn degrees. Based on the profile of the observed morphological alterations, a 15min irradiation was chosen as the exposure time to expose G3, without immobilization, for 5 consecutive days. CONCLUSION: These conditions produced the same morphological changes in the AHM with a shorter solar exposure time, without immobilizing the animals but using environmental exposure fluences, conforming to 3R (reduction - refinement - replacement) recommendations.

Phototoxic assessment of a sunscreen formulation and its excipients: An in vivo and in vitro study.

BACKGROUND: Cosmetic preservatives are used to protect cosmetic formulations and improve its shelf-life. However, these substances may exert phototoxic effects when used under sunlight. OBJECTIVE: To assess safety, efficacy and putative phototoxic effects of a sunscreen formulation SPF 30 and its excipients. MATERIALS/METHODS: Irradiation was performed with solar simulated light (SSL) and the sunscreen from the School of Pharmacy/UFRJ/Brazil. We used albino hairless mice in different groups (control (G1), only irradiated (G2), sunscreen plus irradiation (G3) and vehicle plus irradiation (G4) for morphological assessment and immunefluorescence detection to OKL38. In vitro analyses were with a Saccharomyces cerevisiae (SC) strain plus SSL in the presence of methylparaben, propylparaben, imidazolidinyl urea, aminomethyl propanol and their association. RESULTS: G3 and G4 displayed photosensitization leading to thickening of the epidermis and increased dermal cellularity. G4 displayed strong OKL38 labeling when compared with other groups. Aminomethyl propanol, methylparaben and propylparaben are endowed with phototoxic activity against SC. Propylparaben displayed the highest phototoxic effect, followed by excipients association. CONCLUSIONS: The sunscreen's vehicle is endowed with phototoxic activity. Propylparaben was the most phototoxic agent, increasing the overall phototoxicity of excipient association, pointing to a critical concern regarding vehicle associations intended to cosmetic purposes.

In Vitro and In Vivo Evaluation of DMSO and Azone as Penetration Enhancers for Cutaneous Application of Celecoxib.

BACKGROUND: Celecoxib (CXB) has been explored as an anti-inflammatory or chemopreventive drug for topical treatment of skin diseases and cancer. OBJECTIVE: The main aim of this work was to investigate the potential of dimethylsufoxide (DMSO) and Azone (AZ) as penetration enhancers (P.Es) for topical delivery of CXB. METHOD: The in vitro studies, drug release, skin permeability and potential cytotoxicity/genotoxicity were carried out with formulations containing or not DMSO or AZ (5% and 10%). Skin irritation in rabbits and topical anti-inflammatory activity in mice were assayed in vivo. RESULTS: Skin permeation was minimal while higher retention in stratum corneum (SC) and epidermis plus dermis was found (28.0 and 3-fold respectively) from 10.0% AZ compared to the control indicating a localized CXB effect. CXB associated to 5% or 10% DMSO has shown high drug permeation through skin with low retention. Associations of CXB with both enhancers were not cytotoxic or genotoxic, suggesting safety for cutaneous application. In vivo skin irritation assays of all formulations indicated mild irritation effects and, thus, possible use for longer periods. In vivo anti-inflammatory tests showed that ear edema could be inhibited by CXB associated with 5.0% DMSO (53.0%) or 10.0% AZ (40.0%). These inhibition values were almost 2-fold higher when compared to a commercial formula. CONCLUSION: Although DMSO- associated CXB is an efficient edema inhibitor its high skin permeation suggests risks of systemic effects, whereas association to 10% AZ may improve topical delivery of the drug with good anti-inflammatory activity and no cytotoxic/genotoxic or significant skin irritation effects.

Redox homeostasis of breast cancer lineages contributes to differential cell death response to exogenous hydrogen peroxide.

AIMS: Cancer cells produce higher amounts of reactive oxygen species (ROS) than their normal counterparts. It has been suggested that a further increase in ROS concentration in these cells would lead to oxidative damage-driven death. Thus, we aimed to understand how the intra- and extracellular redox homeostasis differences set cell death response to ROS in breast cancer cell lines. MAIN METHODS: Intra- and extracellular ROS generation was evaluated in tumoral (MCF-7 and MDA-MB-231) and non-tumoral (MCF10A) breast epithelial cells, as well as H2O2 concentration in the culture medium, glutathione peroxidase (GPx), total superoxide dismutase (SOD) and catalase activities, extracellular H2O2 scavenging capacity and total thiol content. Cell viability was determined after H2O2 exposure using the MTT assay. KEY FINDINGS: We have found an increased extracellular ROS production in tumor cells when compared to the non-tumoral lineage. MCF10A cells had higher H2O2 concentration in the extracellular medium. Moreover, extracellular H2O2-scavenging activity was higher in MDA-MB-231 when compared to MCF10A and MCF-7. Regarding intracellular antioxidant activity, a lower GPx activity in tumor cell lines and a higher catalase activity in MDA-MB-231 were observed. Thiol content was lower in MDA-MB-231. Additionally, tumor cell lines were more sensitive to H2O2 exposure than the non-tumoral cells. SIGNIFICANCE: The present report shows that the capability to generate and metabolize ROS differ greatly among the breast cancer cell lines, thus suggesting that redox balance is finely regulated during carcinogenesis. Therefore, our data suggest that therapeutic approaches targeting the redox status might be useful in the treatment of breast tumors.

In vitro and in vivo evaluation of efficacy and safety of photoprotective formulations containing antioxidant extracts

ABSTRACT Chronic exposure to solar radiation could contribute to premature skin aging and skin cancer. Skin presents its own antioxidant defense, however when defenses are out of balance, reactive oxygen species could damage biological structures. In the present work, an oil-in-water photoprotective emulsion was developed and Bauhinia microstachya var. massambabensis Vaz, Fabaceae, extracts at 1% (obtained by extraction with different solvents) were added to this emulsion. In vitro and in vivo efficacy and safety of the formulations were evaluated. Spectrophotometric methods and in vivo Colipa test were performed to evaluated efficacy of the formulations, through sun protection factor (SPF) determination and UVA protection factor assessment. To the in vitro safety assessment HET-CAM, CAM-TBS and Red Blood Cell tests were performed. Results showed that both extracts contributed to a higher in vivo photoprotection (SPF 18) when compared to the formulation without extract (SPF 13), this result could be attributed to the antioxidant activity of the plant extracts that act by capturing reactive oxygen species. Concerning safety, all formulations were considered non-irritant according to in vitro tests. Formulations containing extracts could be considered efficient and safe for cosmetic use since they presented higher sun protection factor and passed the toxicity tests.

Mutagenic and genotoxic potential of direct electric current in Escherichia coli and Salmonella thyphimurium strains.

Direct electric current has several therapeutic uses such as antibacterial and antiprotozoal action, tissues scarring and regeneration, as well as tumor treatment. This method has shown promising results in vivo and in vitro, with significant efficacy and almost no side effects. Considering lack of studies regarding direct electric current mutagenic and/or genotoxic effects, the present work evaluated both aspects by using five different bacterial experimental assays: survival of repair-deficient mutants, Salmonella-histidine reversion mutagenesis (Ames test), forward mutations to rifampicin resistance, phage reactivation, and lysogenic induction. In these experimental conditions, cells were submitted to an approach that allows evaluation of anodic, cathodic, and electro-ionic effects generated by 2 mA of direct electric current, with doses ranging from 0.36 to 3.60 Coulombs. Our results showed these doses did not induce mutagenic or genotoxic effects.

Influence of Ogg1 repair on the genetic stability of ccc2 mutant of Saccharomyces cerevisiae chemically challenged with 4-nitroquinoline-1-oxide (4-NQO).

In Saccharomyces cerevisiae, disruption of genes by deletion allowed elucidation of the molecular mechanisms of a series of human diseases, such as in Wilson disease (WD). WD is a disorder of copper metabolism, due to inherited mutations in human copper-transporting ATPase (ATP7B). An orthologous gene is present in S. cerevisiae, CCC2 gene. Copper is required as a cofactor for a number of enzymes. In excess, however, it is toxic, potentially carcinogenic, leading to many pathological conditions via oxidatively generated DNA damage. Deficiency in ATP7B (human) or Ccc2 (yeast) causes accumulation of intracellular copper, favouring the generation of reactive oxygen species. Thus, it becomes important to study the relative importance of proteins involved in the repair of these lesions, such as Ogg1. Herein, we addressed the influence Ogg1 repair in a ccc2 deficient strain of S. cerevisiae. We constructed ccc2-disrupted strains from S. cerevisiae (ogg1ccc2 and ccc2), which were analysed in terms of viability and spontaneous mutator phenotype. We also investigated the impact of 4-nitroquinoline-1-oxide (4-NQO) on nuclear DNA damage and on the stability of mitochondrial DNA. The results indicated a synergistic effect on spontaneous mutagenesis upon OGG1 and CCC2 double inactivation, placing 8-oxoguanine as a strong lesion-candidate at the origin of spontaneous mutations. The ccc2 mutant was more sensitive to cell killing and to mutagenesis upon 4-NQO challenge than the other studied strains. However, Ogg1 repair of exogenous-induced DNA damage revealed to be toxic and mutagenic to ccc2 deficient cells, which can be due to a detrimental action of Ogg1 on DNA lesions induced in ccc2 cells. Altogether, our results point to a critical and ambivalent role of BER mediated by Ogg1 in the maintenance of genomic stability in eukaryotes deficient in CCC2 gene.

Impact of reduced levels of APE1 transcripts on the survival of patients with urothelial carcinoma of the bladder.

Molecular evidence indicates that alterations in genes involved in the maintenance of genome stability may be related to susceptibility to bladder carcinoma. Our goal was to evaluate the prognostic role of base excision repair (BER) genes in a cohort of patients diagnosed with primary urothelial carcinoma of the bladder (UCB). The levels of all APE1, XRCC1 and POLB transcripts were detected by quantitative real-time PCR (qPCR) technique in tumor samples from 52 patients undergoing transurethral resection (TUR) for primary UCB at the Department of Urology, Brazilian National Cancer Institute, Rio de Janeiro. Increased levels of APE1, XRCC1 and POLB transcripts were significantly associated with high-grade tumors when compared to these levels in low-grade tumors (p<0.01) and could be attributed to different mechanisms of transcriptional regulation as a response to tumorigenesis and oxidative stress. By analyzing the collected data in the present study, regardless of pathological grade or stage, univariate analysis revealed that the reduced levels of APE1 transcripts were significantly associated with cancer-specific mortality (p=0.032). Furthermore, the variant genotype (TG/GG) of the APE1 T1349G polymorphism was observed in 75% of a subset of patients who concomitantly experienced reduced levels of the APE1 transcript and death and/or recurrence events. Taken together, our data reinforce the idea that human DNA repair mechanisms must be finely regulated in order to avoid instability leading to tumorigenesis and poor clinical outcomes in UCB patients.

Antioxidant activity stimulated by ultraviolet radiation in the nervous system of a crustacean.

Ultraviolet (UV) radiation can produce biological damage, principally oxidative stress, by increasing the production of reactive oxygen species (ROS). This study evaluated biochemical impairments related to the oxidative stress induced by UVA, UVB and UVA+UVB (solar simulator-SIM) in environmental doses, during five consecutive days of exposure, in the brain and eyestalk of the crab Ucides cordatus. We evaluated these regions by sampling on the 1st, 3rd and 5th days of UV exposure for lipid peroxidation (LPO), antioxidant capacity against the peroxyl radical (ACAP), and the activities of catalase (CAT), glutathione peroxidase (GPX) and glutathione-S-transferase (GST). Immunohistochemical and immunoblotting assays were performed for anti-activated-caspase 3 in the brains. After the first day of exposure, LPO increased in the eyestalks and brains of the UV-exposed animals; ACAP, and CAT, GPX and GST activities also increased in the brains. On the third day, the LPO values in the eyestalk remained high in the UV-exposed groups, while ACAP decreased in the brain and eyestalk and CAT activity remained high in all irradiated groups in both regions. On the fifth day, LPO decreased in the eyestalk and brain of the UV-exposed groups. These results may have been a consequence of the antioxidant defense system (ADS) activity, since CAT activity was high in both regions, ACAP was high in the eyestalks of the SIM group, and GPX activity remained high in the eyestalks of the UVA and UVB groups. Immunohistochemical assays and immunoblotting showed that there was apoptosis in the brains of the UV-exposed crabs. In conclusion, environmental doses of UV can cause oxidative damage to the CNS cells, including apoptosis.

The anabolic androgenic steroid nandrolone decanoate disrupts redox homeostasis in liver, heart and kidney of male Wistar rats.

The abuse of anabolic androgenic steroids (AAS) may cause side effects in several tissues. Oxidative stress is linked to the pathophysiology of most of these alterations, being involved in fibrosis, cellular proliferation, tumorigenesis, amongst others. Thus, the aim of this study was to determine the impact of supraphysiological doses of nandrolone decanoate (DECA) on the redox balance of liver, heart and kidney. Wistar male rats were treated with intramuscular injections of vehicle or DECA (1 mg.100 g(-1) body weight) once a week for 8 weeks. The activity and mRNA levels of NADPH Oxidase (NOX), and the activity of catalase, glutathione peroxidase (GPx) and total superoxide dismutase (SOD), as well as the reduced thiol and carbonyl residue proteins, were measured in liver, heart and kidney. DECA treatment increased NOX activity in heart and liver, but NOX2 mRNA levels were only increased in heart. Liver catalase and SOD activities were decreased in the DECA-treated group, but only catalase activity was decreased in the kidney. No differences were detected in GPx activity. Thiol residues were decreased in the liver and kidney of treated animals in comparison to the control group, while carbonyl residues were increased in the kidney after the treatment. Taken together, our results show that chronically administered DECA is able to disrupt the cellular redox balance, leading to an oxidative stress state.