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Natural bioactive compounds obtained from microorganisms, have awakened particular interest in the industry nowadays. This attention comes when natural resources depletion is pronounced, and the acquisition of both new plant origin resources and bioactive products, represents a challenge for the next generations. In this sense, prospecting for large-scale production and use of bacterial pigments is a necessary strategy for the development of novel products. A wide variety of properties have been attributed to these substances and, among them, their therapeutic potential against important diseases, such as cancer. There is consensus that available chemotherapy protocols are known to detrimentally affect cancer patients fertility. Hence, considerable part of the deleterious effects of chemotherapy is related to the drugs cytotoxicity, which, in addition to cancer cells, also affect normal cells. Therefore, the intrinsic properties of bacterial pigments associated with low cytotoxicity and relevant cell selectivity, certified them as potential anticancer drugs. However, little information is available about reproductive toxicity of these new and promising compounds. Thus, the present review aims to address the main bacterial pigments, their potential uses as anticancer drugs and their possible toxic effects, especially on the female gonad.

Os compostos bioativos naturais obtidos de microrganismos têm despertado especial interesse da indústria nos últimos anos. Esta atenção ocorre em um momento em que o esgotamento de recursos naturais é pronunciado, e a aquisição de novos insumos e produtos bioativos de origem vegetal representa um desafio para as próximas gerações. Neste sentido, a prospecção para a produção e uso em larga escala dos pigmentos bacterianos tem representado uma importante estratégia para o desenvolvimento de novos produtos. Uma grande variedade de propriedades foi atribuída a estas substâncias, entre elas, o potencial terapêutico contra doenças importantes, como o câncer. Existe um consenso de que os protocolos quimioterápicos disponíveis são conhecidos por afetarem negativamente a fertilidade de pacientes com câncer. Grande parte dos efeitos deletérios da quimioterapia está relacionado à citotoxicidade das drogas usadas para este fim, que além das células cancerosas, afetam as células normais. Nesse sentido, as propriedades naturais atribuídas aos pigmentos bacterianos associadas à baixa citotoxicidade e relevante seletividade, os qualificaram como potenciais drogas anticâncer. No entanto, pouco se tem de informação a respeito da toxicidade reprodutiva destes novos e promissores compostos. Dessa forma, a presente revisão tem o objetivo de abordar os principais pigmentos bacterianos, suas utilizações potenciais como drogas anticâncer, bem como os seus possíveis efeitos tóxicos, sobretudo, sobre a gônada feminina.

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A aquicultura moderna é um dos setores de produção de alimentos que mais cresce no mundo. A tilápia, além de possuir grandes vantagens produtivas, origina produtos com grande aceitação pelo mercado. Em sua nutrição, podem ser utilizados aditivos com finalidades zootécnicas, pigmentantes ou antioxidantes. Este estudo objetivou avaliar o efeito da suplementação da dieta de tilápias com biomassa de Rubrivivax gelatinosus sobre o desempenho zootécnico e a saúde dos animais (histologia e hematologia) e sobre as características de qualidade dos filés (pH, composição químico-bromatológica, cor e rancidez). O experimento contou com seis tratamentos, compostos de um grupo controle, sem aditivos, um grupo contendo pigmentante comercial e quatro grupos com a biomassa nas concentrações de 175, 350, 700 e 1400mg/kg. Peixes pesando 21,42±5,65g foram criados por 74 dias em sistema com recirculação de água e, posteriormente, foram abatidos para a realização das análises. Não foram encontradas diferenças para os resultados das análises de desempenho, histológicas e hematológicas. Os filés dos grupos alimentados com os aditivos apresentaram menor umidade que o grupo controle, e os filés dos grupos alimentados com biomassa apresentaram as maiores teores proteicos. Não houve diferenças entre os tratamentos para os valores de pH, lipídeos e cinzas. Quanto à cor dos filés, todos os tratamentos com aditivos aumentaram a intensidade de vermelho. Em todos os tratamentos, a rancidez dos filés foi crescente durante o armazenamento, embora em menores valores nos filés dos grupos tratados com as maiores concentrações de biomassa. A biomassa de R. gelatinosus não promoveu alterações no desempenho nem na saúde animal e mostrou-se capaz de melhorar os aspectos de qualidade e conservação dos filés.

Modern aquaculture is one of the fastest growing food sectors in the world. Beyond having productivity advantages, tilapia fish yields products with great market acceptance. For its nutrition, additives aiming at increasing zootechnical, pigmenting or antioxidant features may be used. This study aimed to evaluate the effect of the supplementation of tilapia diets with Rubrivivax gelatinosus biomass on the performance and the health of animals (histology and hematology), and on the quality of fillets (pH, proximate composition, color and rancidity). The experiment comprised six treatments, made of a control group with no additives, a group containing commercial pigments and four groups with biomass at 175, 350, 700 and 1400 mg/kg. Fish weighing 21.42±5.65g were reared for 74 days in a system with water recirculation and slaughtered for analyzes. No differences were detected for performance, histological and hematological analyzes. Fillets of the groups fed additives had lower moisture content than the control group while the fillets of the groups fed the biomass had the highest protein percentages. No differences were detected among treatments for pH​, lipids and ash values. Regarding to the color of the fillets, all treatments with additives increased redness. For all treatments, rancidity in the fillets increased during storage, although the groups treated with the highest biomass concentrations had the lowest values. R. gelatinosus biomass did not change performance and animal health, and proved to be capable of improving fillets quality features and conservation.

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A aquicultura moderna é um dos setores de produção de alimentos que mais cresce no mundo. A tilápia, além de possuir grandes vantagens produtivas, origina produtos com grande aceitação pelo mercado. Em sua nutrição, podem ser utilizados aditivos com finalidades zootécnicas, pigmentantes ou antioxidantes. Este estudo objetivou avaliar o efeito da suplementação da dieta de tilápias com biomassa de Rubrivivax gelatinosus sobre o desempenho zootécnico e a saúde dos animais (histologia e hematologia) e sobre as características de qualidade dos filés (pH, composição químico-bromatológica, cor e rancidez). O experimento contou com seis tratamentos, compostos de um grupo controle, sem aditivos, um grupo contendo pigmentante comercial e quatro grupos com a biomassa nas concentrações de 175, 350, 700 e 1400mg/kg. Peixes pesando 21,42±5,65g foram criados por 74 dias em sistema com recirculação de água e, posteriormente, foram abatidos para a realização das análises. Não foram encontradas diferenças para os resultados das análises de desempenho, histológicas e hematológicas. Os filés dos grupos alimentados com os aditivos apresentaram menor umidade que o grupo controle, e os filés dos grupos alimentados com biomassa apresentaram as maiores teores proteicos. Não houve diferenças entre os tratamentos para os valores de pH, lipídeos e cinzas. Quanto à cor dos filés, todos os tratamentos com aditivos aumentaram a intensidade de vermelho. Em todos os tratamentos, a rancidez dos filés foi crescente durante o armazenamento, embora em menores valores nos filés dos grupos tratados com as maiores concentrações de biomassa. A biomassa de R. gelatinosus não promoveu alterações no desempenho nem na saúde animal e mostrou-se capaz de melhorar os aspectos de qualidade e conservação dos filés.(AU)

Modern aquaculture is one of the fastest growing food sectors in the world. Beyond having productivity advantages, tilapia fish yields products with great market acceptance. For its nutrition, additives aiming at increasing zootechnical, pigmenting or antioxidant features may be used. This study aimed to evaluate the effect of the supplementation of tilapia diets with Rubrivivax gelatinosus biomass on the performance and the health of animals (histology and hematology), and on the quality of fillets (pH, proximate composition, color and rancidity). The experiment comprised six treatments, made of a control group with no additives, a group containing commercial pigments and four groups with biomass at 175, 350, 700 and 1400 mg/kg. Fish weighing 21.42±5.65g were reared for 74 days in a system with water recirculation and slaughtered for analyzes. No differences were detected for performance, histological and hematological analyzes. Fillets of the groups fed additives had lower moisture content than the control group while the fillets of the groups fed the biomass had the highest protein percentages. No differences were detected among treatments for pH​, lipids and ash values. Regarding to the color of the fillets, all treatments with additives increased redness. For all treatments, rancidity in the fillets increased during storage, although the groups treated with the highest biomass concentrations had the lowest values. R. gelatinosus biomass did not change performance and animal health, and proved to be capable of improving fillets quality features and conservation.(AU)

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The mutagenic activity of garbage originating from a household wax industry was determined by the Salmonella/microsome assay, using the bacterial strains TA100, TA98 and YG1024. The garbage was obtained by sweeping the floor of the factory at the end of the work shift. Organic compounds were extracted by ultrasound for 30 min in dichloromethane or 70% ethanol. After evaporation of solvent, these extracts (HFS: household-wax factory sweepings) were dissolved in DMSO, and were tested for the mutagenic activity at varying concentrations (HFS-ET: 0.08-0.68 mg/plate, HFS-DCM: 0.60-7.31 mg/plate). The colouring agents (pigments) used in the production of the wax were also dissolved in DMSO and tested with the assay. The concentrations tested for each pigment were: Amaranth: 0.46-3.65 mg/plate, Auramine: 0.15-1.2 mg/plate and Rhodamine B: 0.22-1.82 mg/plate. Both ET and DCM organic extracts had mutagenic activity, especially in the YG1024 strain. The pigments behaved in a similar way, demonstrating that YG1024 was the most sensitive strain for the detection of mutagenicity, and that metabolization increased the activity. Human exposure (occupational and non-occupational) to industrial residues generated during the household-wax manufacturing and packaging process should be monitored, since this type of garbage is normally deposited in the environment without any control.

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Oxidative stress induced by ciprofloxacin and pyoverdin, a leukotoxic pigment, was studied by comparing their effect in bacteria and leukocytes. Chemiluminescence (CL) assays with lucigenin or luminol were adapted to measure the stimuli of superoxide anion (O2 -) and other reactive species of oxygen (ROS) in bacteria. Ciprofloxacin principally induced the production of O2 - in the three species studied: Staphylococcus aureus, Enterococcus faecalis and Escherichia coli. Lucigenin CL assay showed high oxidative stress in S. aureus due to its low superoxide dismutase (SOD) activity, whereas E. coli exhibited important SOD activity, responsible for little production of O2 - in absence or presence of ciprofloxacin. Reduction of nitroblue of tetrazolium (NBT) was applied. This assay indicated that there was higher oxidative stress in S. aureus and E. faecalis than in E. coli. The comparison of oxidative stress generated in bacteria and leukocytes was used to check the selective toxicity of ciprofloxacin in comparison with pyoverdin. Ciprofloxacin did not generate significant stimuli of O2 - in neutrophils, while pyoverdin duplicated the production of O2 -. CL and NBT were useful to study the leukotoxicity of ciprofloxacin. Oxidative stress caused by the antibiotic and the leukotoxic pigment was similar in bacteria.

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The effect of three forms pyoverdin on mouse liver was studied. Significant increases of alanine amino transferase (ALT) and aspartate amino transferase (AST) were obtained in mice after ingestion of water with forms A and C. The effect on liver was more evident with A than with C. Pyoverdin was purified by means of salt saturation, solvent extractions and ion-exchange chromatography. Fluorescent peaks obtained in the presence of light were different from those eluted under dark conditions. The relative amounts of pyoverdin A, B and C varied when dark purification procedure was employed. Form A decreased while C increased in the absence of light. Optimum conditions for C were in the dark without iron. When C was exposed to light, it changed to form A. Fast Atom Bombardment (FAB) mass spectrometry of pyoverdin form C gave a form at M+ = 1324 m.u., which is 9 m.u. less than pyoverdin purified in the presence of light. The results suggest that light can influence pyoverdin stability and toxicity.

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Pseudomonas fluorescens PAB strain produced pyoverdine in a synthetic medium, this pigment was purified by solvent extraction and ion exchange, then sterilized by filtration. Where cytotoxic effect on human leukocytes was assayed, death and lysis was observed. Sublytic doses decreased leukocytes phagocytosis and chemotaxis. Bacteria grew and produced pigment in blood stored a 4 degrees C, with a pyoverdine production of 0.13 mg/ml of serum after 5 days of incubation.

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The biosynthetic pigment from Chromobacterium violaceum BB-78, 1,3-dihydro-2H-indol-2-one and its derivatives exhibit biological activities such as antimicrobial action, low hemolytic effects on red blood cells and in vitro trypanocide activity. A relatively high cytotoxicity on V-79 hamster fibroblast cells of the biosynthetic pigment was found, although with the methylol derivative the toxicity was almost eliminated. The methylol derivative exhibited similar toxicity as Nifurtimox, a known, commercial trypanocide compound.

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The biosynthetic pigment from Chromobacterium violaceum BB-78, 1,3-dihydro-2H-indol-2-one and its derivatives exhibit biological activities such as antimicrobial action, low hemolytic effects on red blood cells and in vitro trypanocide activity. A relatively high cytotoxicity on V-79 hamster fibroblast cells of the biosynthetic pigment was found, although with the methylol derivative the toxicity was almost eliminated. The methylol derivative exhibited similar toxicity as Nifurtimox, a known, commercial trypanocide compound

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