RESUMO
Trichomoniasis is the most common non-viral sexually transmitted infection (STI) in the world caused by Trichomonas vaginalis. Failures in the treatment with the 5-nitroimidazole class including parasite resistance to metronidazole elicit new alternatives. Marine natural products are sources of several relevant molecules, presenting a variety of metabolites with numerous biological activities. In this work, we evaluated the anti-T. vaginalis activity of fungi associated with marine invertebrates by mass spectrometry-based metabolomics approaches. After screening of six marine fungi, extract from Penicillium citrinum FMPV 15 has shown to be 100% active against T. vaginalis, and the gel permeation column on Sephadex LH-20® yielded twelve organic fractions which five showed to be active. Metabolomics and statistical analyses were performed with all the samples (extract and fractions), and several compounds were suggested to be related to the activity. These components include citrinin, dicitrinin C, citreoisocoumarin, dihydrocitrinone, decarboxycitrinin, penicitrinone C, and others. The minimum inhibitory concentration (MIC) value of anti-T. vaginalis activity of citrinin was 200 µM. The marine fungi metabolites show potential as new alternatives to overcome drug resistance in T. vaginalis infections.
Assuntos
Produtos Biológicos , Citrinina , Trichomonas vaginalis , Fungos , Espectrometria de Massas , Metronidazol/farmacologia , Extratos VegetaisRESUMO
Breast cancer is one of the most lethal types of cancer and a leading cause of mortality among Women worldwide. Citrinin (CIT), a polyketide extracted from the fungus Penicillium citrinum, exhibits a wide range of biological activities such as antibacterial, antifungal, and cytotoxic effects. The aim of the current study was to evaluate the antitumoral effects of CIT against 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinoma in Swiss mice For this, CIT, DMBA and the standard cyclophosphamide (CPA) induced behavioral changes in experimental animals, and these changes were screened by using the rota rod and open field tests. Additionally, hematological, biochemical, immuno-histochemical, and histopathological analyses were carried out. Results suggest that CIT did not alter behavioral, hematological, and biochemical parameters in mice. DMBA induced invasive mammary carcinoma and showed genotoxic effects in the breasts, bone marrow, lymphocytes, and hepatic cells. It also caused mutagenic effects in the formation of micronuclei, bridges, shoots, and binucleate cells in bone marrow and liver. CIT and CPA genotoxic effects were observed after 3 weeks of therapy, where CIT exhibited a repair capacity and induced significant apoptotic damage in mouse lymphocytes. In conclusion, CIT showed antitumoral effects in Swiss mice, possibly through induction of apoptosis.
Assuntos
Antineoplásicos/farmacologia , Citrinina/farmacologia , Neoplasias Experimentais/tratamento farmacológico , Penicillium/química , 9,10-Dimetil-1,2-benzantraceno , Animais , Apoptose/efeitos dos fármacos , Ciclofosfamida/farmacologia , Dano ao DNA/efeitos dos fármacos , Feminino , Camundongos , Mutagênicos , Neoplasias Experimentais/químicaRESUMO
Citrinin (CIT) is a cytotoxic, hepatotoxic, nephrotoxic and cardiotoxic metabolite obtained from Penicillium citrinum, that has been increasingly searched as an anticancer drug candidate. In this study, we assessed the antitumor effects of citrinin, using cytogenetic biomarkers for genotoxicity in Sarcoma 180 (S-180) ascitic fluid cells of mice. Citrinin, extracted from P. citrinum acetonitrile extract, was characterized by LC-MS. Cytotoxic assessment was done through using comet (alkaline version) and micronucleus assays. In S-180 cells, CI50 of CIT was 3.77 µg/mL, while at 12.5 and 100 µg/mL, CIT was as cytotoxic as doxorubicin (2 µg/mL). At 0.5, 1.0 and 2.0 µg/mL, it induced genotoxicity and mutagenicity in S-180 cells, especially at 2 µg/mL, triggering oxidative damage similar to hydrogen peroxide (10 mM). The antitumor effects were evidenced by a marked increase in S-180 cells apoptosis and necrosis due to clastogenic and/or aneugenic cytogenetic effects (micronucleus formation), as well as by induction of nucleoplasm bridges and nuclear buds, culminating in S-180 apoptosis and necrosis. CIT has potential as drug candidate for antitumor purposesbyinvolving cytogenetic mechanisms.
Assuntos
Antineoplásicos/uso terapêutico , Citrinina/uso terapêutico , Análise Citogenética , Sarcoma 180/tratamento farmacológico , Sarcoma 180/genética , Animais , Antineoplásicos/farmacologia , Ascite/patologia , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citrinina/isolamento & purificação , Citrinina/farmacologia , Modelos Animais de Doenças , Camundongos , Mutagênicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Penicillium/químicaRESUMO
Citrinin (CIT) is a mycotoxin which causes contamination in the food and is associated with different toxic effects. A web search on CIT has been conducted covering the timespan since 1946. The accumulated data indicate that CIT is produced by several fungal strains belonging to Penicillium, Aspergillus and Monascus genera, and is usually found together with another nephrotoxic mycotoxin, ochratoxin A. Although, it is evident that CIT exposure can exert toxic effects on the heart, liver, kidney, as well as reproductive system, the mechanism of CIT-induced toxicity remains largely elusive. It is still controversial what are the genotoxic and mutagenic effects of CIT. Until now, its toxic effect has been linked to the CIT-mediated oxidative stress and mitochondrial dysfunction in biological systems. However, the toxicity strongly depends on its concentration, route, frequency and time of exposure, as well as from the used test systems. Besides the toxic effects, CIT is also reported to possess a broad spectrum of bioactivities, including antibacterial, antifungal, and potential anticancer and neuro-protective effects in vitro. This systematic review presents the current state of CIT research with emphasis on its bioactivity profile.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Citrinina/química , Citrinina/farmacologia , Animais , Citrinina/síntese química , Dano ao DNA/efeitos dos fármacos , Contaminação de Alimentos/análise , Humanos , Estresse Oxidativo/efeitos dos fármacosRESUMO
Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) have been frequently associated with bacterial resistance mechanisms. These mechanisms, in turn, restrict a range of therapeutic opportunities for the treatment of infections caused by these micro-organisms. Faced with this problem, the present study aims to isolate and characterize molecules with antimicrobial activity derived from the fungus Penicillium citrinum isolated from Cerrado soil. Furthermore, we also tested possible antibacterial potential alone and in combination with commercial antimicrobial agents. In this context, citrinin was isolated and characterized by nuclear magnetic resonance and electrospray ionization. Functional analyses showed MIC of 128 µg ml-1 against S. aureus ATCC 25923, E. faecalis ATCC 29212 and a clinical isolate of vancomycin-resistant E. faecium (VRE01). However, for a clinical strain of methicillin-resistant S. aureus (MRSA01), the MIC was 256 µg ml-1. In order to avoid such high concentrations and reduce the collateral effects, additive effects were evidenced by combining citrinin with cefoxitin against MRSA01 (FIC index=0.5) and also citrinin with vancomycin toward VRE01 (FIC index=0.5). In vivo studies with BALB/c-tipe mice (MRSA assay) demonstrated a clinical ineffectiveness of cefoxitin associated with citrinin (9.8 mg kg-1 of cefoxitin +0.2 mg kg-1 of citrinin), with this combination being inefficient to increase animal survival. However, the combination used in the treatment of VRE (23.5 mg kg-1 of citrinin +1.5 mg kg-1 of vancomycin) sepsis model was extremely promising, leading to an animal survival rate of 80 percent. In summary, our data show, for the first time, the possible successful use of citrinin associated with vancomycin for pathogenic bacteria control.
Assuntos
Antibacterianos/farmacologia , Citrinina/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Penicillium/química , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Vancomicina/farmacologia , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/toxicidade , Cefoxitina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Citrinina/isolamento & purificação , Citrinina/toxicidade , Sinergismo Farmacológico , Feminino , Dose Letal Mediana , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Penicillium/citologia , Células RAW 264.7 , Testes de ToxicidadeRESUMO
A study was conducted to determine the incidence and levels of mycotoxins in the main staple foods of three indigenous people of the Colombian Amazon. A total of 20 corn, 24 rice and 59 cassava samples were analysed by a multi-analyte liquid chromatography-tandem mass spectrometry method covering the major classes of mycotoxins. In addition, cassava samples were also analysed for cyanogenic glycosides. The indigenous Amazon communities tested are exposed to potentially carcinogenic mycotoxins (particularly aflatoxins), as well as other mycotoxins, mainly through the intake of locally grown corn. Citrinin content in this corn was unusually high and has not been reported elsewhere. Two cassava samples contained high levels of cyanogenic glycosides. It is strongly recommended not to grow corn in the Amazon but instead purchase it from vendors capable of guaranteeing mycotoxin levels below the maximum allowable concentration in Colombia.
Assuntos
Contaminação de Alimentos/análise , Glicosídeos/análise , Indígenas Sul-Americanos , Manihot/química , Micotoxinas/análise , Oryza/química , Zea mays/química , Carcinógenos/análise , Citrinina/análise , Colômbia , Dieta , Exposição Ambiental , HumanosRESUMO
The efficacy of different concentrations of aqueous neem leaf extract (3.12 to 50 mg/mL) on growth and citrinin production in three isolates of Penicillium citrinum was investigated under laboratory conditions. Mycotoxin production by the isolates was suppressed, depending on the concentration of the plant extract added to culture media at the time of spore inoculation. Citrinin production in fungal mycelia grown for 21 days in culture media containing 3.12 mg/mL of the aqueous extract of neem leaf was inhibited by approximately 80% in three isolates of P. citrinum. High-performance liquid chromatography was performed to confirm the spectrophotometric results. Vegetative growth was assessed, but neem extract failed to inhibit it. Neem leaf extract showed inhibition of toxin production without retardation in fungal mycelia growth.
RESUMO
Avaliou-se o efeito imunotóxico causado por exposição a baixas doses de citrinina (2,5mg kg-1) em camundongos albinos expostos à micotoxina antes (n=15), durante (n=15) e após (n=15) a imunização com antígeno inerte, representado por eritrócitos de carneiro sheep red blood cells (SRBC). Quinze camundongos foram usados como controle (não intoxicados). Sete dias após o tratamento, os animais foram sangrados e os títulos de anticorpos anti-SRBC e de complemento foram determinados. A citrinina diminuiu os títulos de anticorpos primários em todos os grupos intoxicados. A intoxicação antes e após a imunização provocou diminuição em 87,5% nos títulos médios de anticorpos específicos. A exposição simultânea à imunização gerou diminuição de 75%. Houve acentuada redução nos níveis de complemento circulante, detectada nos animais previamente intoxicados (93,8%), ou intoxicados juntamente com a imunização (87,5%).(AU)
The immunotoxic effect caused by citrinin was evaluated in albino mice exposed to a single dose of 2.5mg.kg-1 before (n=15), concomitantly (n=15) and after (n=15) immunization with an inert antigen represented by sheep red blood cells (SRBC). The animals were bleed seven days following the mycotoxin exposure for antibodies anti-SRBC and complement titration and compared to results obtained from non-exposed controls (n=15). It was detected a decreasing antibodies titration in all the intoxicated animals. Those animals that received citrinin before and after SRBC sensitization equally presented a lowering of 87.5% on the primary antibodies level. The exposure to the mycotoxin simultaneously to the SRBC sensitization caused a decrease equivalent to 75%. A remarkable effect was also demonstrated for the circulating complement in both groups of animals, with a decrease of 87.5% on those intoxicated before and of 93.8% on those treated concomitantly to the SRBC sensitization.(AU)
Assuntos
Animais , Citrinina/efeitos adversos , Citrinina/toxicidade , Cumarínicos/toxicidade , Cumarínicos/administração & dosagem , Citrinina/administração & dosagem , Camundongos , Terapia de ImunossupressãoRESUMO
Toxigenic fungi were studied in beans (Phaseolus vulgaris L.) of Classes black and color, cultivated in different regions of the State of Santa Catarina, south region of Brazil. The mean counts of filamentous fungi were 2.8 x 103 and 6.7 x 103 CFU/g for beans Classes black and color, respectively. Penicillium spp., Aspergillus spp. and Phoma spp. were the most frequent genera isolated, followed by Ryzopus spp., Alternaria spp., Helminthosporium spp., Cladosporium spp., Botrytis spp., Fusarium spp., Trichoderma spp., Curvularia spp. and Dreschelera spp. Among beans Class black, 24.6% of the Aspergillus strains produced mycotoxins: 13.1% produced aflatoxins (AFs); 11.5% produced ochratoxin A (OTA) and 28.9% of Penicillium produced citrinin (CTR). On the other hand, 22.1% of Aspergillus strains isolated from beans Class color produced mycotoxins (16.7% produced AFs and 5.4% produced OTA), while Penicillium genera had 35.4% of CTR producing strains. The toxigenic species were A. flavus, A. parasiticus, A. ochraceus and P. citrinum Thom.
Foram estudados fungos toxigênicos em feijão (Phaseolus vulgaris L.), classes preto e cores, cultivados em diferentes regiões do Estado de Santa Catarina, região Sul do Brasil. A média total de fungos filamentosos foi de 2,8x10³ e 6,7x10³ UFC/g para feijão classe preto e cores, respectivamente. Penicillium spp., Aspergillus spp. e Phoma spp. foram os gêneros mais frequentes isolados, seguidos por Ryzopus spp., Alternaria spp., Helminthosporium spp., Cladosporium spp., Botrytis spp., Fusarium spp., Trichoderma spp., Curvularia spp. e Dreschelera spp. No feijão classe preto, 24,6% das cepas de Aspergillus isolados eram toxigenicas: 13.1% eram produtoras de aflatoxinas (AFs) e 11,5% de ocratoxina A (OTA); e 28,9% de Penicillium produziram citrinina (CTR). Por outro lado, 22,1% de cepas de Aspergillus isolados do feijão classe cores, produziram micotoxinas (16,7% produziram AF e 5,4% produziram OTA), já do gênero Penicillium, 35,4% das cepas produziram CTR. As espécies toxigênicas isoladas foram A. flavus, A. parasiticus, A. ochraceus e P. citrinum Thom.
RESUMO
A study on the occurrence of citrinin and citrinin production ability of Penicillium spp. isolated from decaying apples collected from households in Croatia was carried out. Among 100 samples of apples, 37 strains of Penicillium spp. were found, including P. expansum, P. roqueforti, P. implicatum and P. purpurogenum. Citrinin production in liquid yeast medium by 11 strains of P. expansum varied in a range of 0.07 to 9.00 mg.kg-1. Citrinin was isolated from 19% of apple samples in range of 0.05 to 0.24 mg.kg-1. Antimicrobial activity of isolated citrinin, evaluated through tests on Bacillus subtilis, presented inhibitory zones varying from 5 mm to 1 cm. Minimal inhibitory concentrations (MIC) were 0.0072 µg.mL-1 for bacteriostatic effect, and 0.0144 µg.mL-1 for bactericidal effect.
Nesse estudo, foi examinada a ocorrência de citrinina e a capacidade de produção do citrinina por cepas de Penicillum spp. isoladas de maçãs deterioradas, recolhidas em pomares domésticos no território da Croácia. De 100 amostras de maçãs examinadas, foram isoladas 37 cepas de Penicillium spp. incluindo P. expansum, P. roqueforti, P. impicatum e P. purpurogenum. A capacidade de produção de citrinina por 11 cepas de P. expansun foi determinada em meio líquido obtendo-se concentrações variando entre 0,07 e 9,00 mg.kg-¹. A citrinina foi detectada em 19% das amostras de maçãs, com concentração variando entre 0,05 e 0,24 mg.kg-¹. O efeito antimicrobiano da citrinina foi determinado em testes com Bacillus subtilis, com zona de inibição variando entre 5 mm e 1 cm. A concentração mínima inibitória (CMI) foi 0,0072 µg.mL-1 para o efeito bacteriostático e 0,0144 µg.mL-1 para o efeito bactericida.