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1.
Ecotoxicol Environ Saf ; 208: 111725, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396056

RESUMO

Aflatoxin B1 (AFB1) is a potent hepatotoxic and carcinogenic agent. Curcumin possesses potential anti-inflammatory, anti-oxidative and hepatoprotective effects. However, the role of LncRNAs in the protective mechanisms of curcumin against AFB1-induced liver damage is still elusive. Experimental broilers were randomly divided into 1) control group, 2) AFB1 group (1 mg/kg feed), 3) cur + AFB1 group (1 mg/kg AFB1 plus 300 mg/kg curcumin diet) and 4) curcumin group (300 mg/kg curcumin diet). Liver transcriptome analyses and qPCR were performed to identify shifts in genes expression. In addition, histopathological assessment and oxidant status were determined. Dietary AFB1 caused hepatic morphological injury, significantly increased the production of ROS, decreased liver antioxidant enzymes activities and induced inflammation and apoptosis. However, dietary curcumin partially attenuated the abnormal morphological changes, oxidative stress, and apoptosis in liver tissues. Transcriptional profiling results showed that 34 LncRNAs and 717 mRNAs were differentially expressed with AFB1 and curcumin co-treatment in livers of broilers. Analysis of the LncRNA-mRNA network, GO and KEGG enrichment data suggested that oxidative stress, inflammation and apoptosis pathway were crucial in curcumin's alleviating AFB1-induced liver damage. In conclusion, curcumin prevented AFB1-induced oxidative stress, inflammation and apoptosis through LncRNAs. These results provide new insights for unveiling the protective mechanisms of curcumin against AFB1-induced liver damage.


Assuntos
Aflatoxina B1/toxicidade , Curcumina/farmacologia , Fígado/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Galinhas/metabolismo , Dieta , Inflamação/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/farmacologia
2.
Ecotoxicol Environ Saf ; 209: 111823, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33360594

RESUMO

Aflatoxin is a known mycotoxin that pollutes various grains widely in the environment. Aflatoxin B1 (AFB1) and Aflatoxin M1 (AFM1) have been shown to induce cytotoxicity in many cells, yet their effects on mammary epithelial cells remain unclear. In this study, we examined the toxicity and the effects of AFB1 and AFM1 on bovine mammary epithelial cells (BME cells). The cells were treated with AFB1 or AFM1 at a concentration of 0-10 mg/L for 24 or 48 h, followed by cytotoxicity assays, flow cytometry, and transcriptomics. Our results demonstrated that AFB1 and AFM1 induced cell proliferation inhibition, apoptosis and cell cycle arrest. However, the level of intracellular reactive oxygen species has no significant difference. The RNA-Seq results also showed that AFB1 and AFM1 changed many related gene expressions like apoptosis and oxidative stress, cycle, junction, and signaling pathway. Taken together, AFB1 and AFM1 were found to affect cytotoxicity and related gene changes in BME cells. Notably, this study reported that 2 mg/L of AFB1 and AFM1 affected the expression of methylation-related genes, and ultimately altered the rate of m6A methylation in RNA. It may provide a potential direction for toxins to indirectly regulate gene expression by affecting RNA methylation modification. Our research provides some novel insights and data about AFB1 and AFM1 toxicity in BME cells.


Assuntos
Aflatoxina B1/toxicidade , Aflatoxina M1/toxicidade , Testes de Toxicidade , Transcriptoma/fisiologia , Animais , Apoptose/efeitos dos fármacos , Bovinos , Contagem de Células , Proliferação de Células , Células Epiteliais/efeitos dos fármacos , Feminino , Citometria de Fluxo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio
3.
PLoS One ; 15(9): e0239479, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32966310

RESUMO

Mycotoxin management in agriculture is an essential challenge for maintaining the health of both animals and humans. Choosing the right adsorbent is still a question for many breeders and an important criterion for feed manufacturers. New adsorbents are still being sought. Graphene oxide is a promising material in the field of nanotechnology, which excels in its adsorption properties. Presented in vitro study investigates graphene oxide for the binding of mycotoxins from crushed wheat. The results show that graphene oxide has an adsorption capacity for aflatoxin 0.045 mg/g, zearalenone 0.53 mg/g and deoxynivalenol 1.69 mg/g at 37° C. In vitro simulation of crushed wheat digestion showed rapid adsorption during the gastric phase. Of the minerals, Mg, Cu and Zn were the most adsorbed. The applied dose of graphene oxide of 10 mg/g caused only a slight inhibition of the digestive enzymes α-amylase and trypsin compared to pepsin and gastric lipase. In vitro results indicated the suitability of graphene oxide in the adsorption of the aflatoxin, zearalenone and deoxynivalenol.


Assuntos
Grafite/química , Micotoxinas/isolamento & purificação , Adsorção , Aflatoxina B1/isolamento & purificação , Aflatoxina B1/toxicidade , Ração Animal/análise , Ração Animal/toxicidade , Animais , Digestão , Contaminação de Alimentos/análise , Contaminação de Alimentos/prevenção & controle , Absorção Gastrointestinal , Humanos , Técnicas In Vitro , Micotoxinas/toxicidade , Nanoestruturas/química , Tricotecenos/isolamento & purificação , Tricotecenos/toxicidade , Triticum/química , Triticum/toxicidade , Zearalenona/isolamento & purificação , Zearalenona/toxicidade
4.
PLoS One ; 15(9): e0239540, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32966316

RESUMO

Aflatoxin B1 (AFB1), a mycotoxin, is acutely hepatotoxic to many animals including humans. However, there are marked interspecies differences in sensitivity to AFB1-induced toxicity depending on bioactivation by cytochrome P450s (CYPs). In the present study, we examined the applicability of chimeric mice with humanized livers and derived fresh human hepatocytes for in vivo and vitro studies on AFB1 cytotoxicity to human hepatocytes. Chimeric mice with highly humanized livers and SCID mice received daily injections of vehicle (corn oil), AFB1 (3 mg/kg), and carbon tetrachloride (50 mg/kg) for 2 days. Histological analysis revealed that AFB1 promoted hepatocyte vacuolation and inflammatory cell infiltration in the area containing human hepatocytes. A novel human alanine aminotransferase 1 specific enzyme-linked immunosorbent assay demonstrated the acute toxicity of AFB1 to human hepatocytes in the chimeric mouse livers. The sensitivity of cultured fresh human hepatocytes isolated from the humanized liver mice for AFB1 cytotoxicity was comparable to that of primary human hepatocytes. Long-term exposure to AFB1 (6 or 14 days) produced a more severe cytotoxicity. The half-maximal lethal concentration was 10 times lower in the 2-week treatment than after 2 days of exposure. Lastly, the significant reduction of AFB1 cytotoxicity by a pan-CYP inhibitor or transfection with CYP3A4 specific siRNA clearly suggested that bioactivation of AFB1 catalyzed by CYPs was essential for AFB1 cytotoxicity to the human hepatocytes in our mouse model. Collectively, our results implicate the humanized liver mice and derived fresh human hepatocytes are useful models for studies of AFB1 cytotoxicity to human hepatocytes.


Assuntos
Aflatoxina B1/toxicidade , Hepatócitos/efeitos dos fármacos , Ativação Metabólica , Aflatoxina B1/administração & dosagem , Aflatoxina B1/farmacocinética , Animais , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Hepatócitos/patologia , Hepatócitos/transplante , Humanos , Técnicas In Vitro , Dose Letal Mediana , Transplante de Fígado , Masculino , Camundongos , Camundongos SCID , RNA Interferente Pequeno/genética , Quimeras de Transplante , Vacúolos/efeitos dos fármacos , Vacúolos/patologia
5.
Toxicon ; 186: 109-119, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32805295

RESUMO

To investigate the effects of oral administration of probiotics consortium on lipid metabolism in aflatoxin B1 (AFB1) exposed rats, ninety female albino rats were first grouped into two: NC (control fed standard feed) and AF (fed AFB1-contaminated feed at 40 ppb). After eight weeks, baseline animals were sacrificed from both groups while the others further divided into four groups - NC treated with and without the probiotics consortium, aflatoxin treated with and without the probiotics consortium (NCT, NCC, AFT, and AFC respectively). Five animals from each group were sacrificed weekly for four weeks, with the collection of blood, liver, brain, and the small intestine. Administration of probiotics instigated significant (p < 0.05) reductions in the elevated plasma and organ lipids as well as HDL-TAG and VLDL + LDL CHO concentrations of animals exposed to AF. AF-induced hepatic lipogenesis and up-regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity were also significantly (p < 0.05) attenuated following treatment with probiotics in a time-dependent manner. Moreover, neither AF nor probiotics had any effect on glycerol-3-phosphate acyltransferase. Lipid peroxidation was significantly (p < 0.05) reduced in probiotics-treated AF groups, compared to the AF-control groups. This study indicates that the probiotic consortium used synergistically ameliorated the AFB1-induced disruptions in lipid metabolism.


Assuntos
Aflatoxina B1/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Probióticos , Administração Oral , Animais , Feminino , Peroxidação de Lipídeos , Fígado , Ratos
6.
Ecotoxicol Environ Saf ; 203: 110899, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32678747

RESUMO

Liver is the earliest target for AFB1 toxicity in both human and animals. In the last decade, plant derived by-products have been used in animal feed to reduce AFB1 induced toxicity. In the present study we investigated whether the presence of 8% grape seed meal by-product is able to counteract the hepatotoxic effects produced by AFB1 in liver of pig after weaning exposed to the toxin through the contaminated feed for 28 days. Twenty four weaned cross-bred TOPIGS-40 piglets with an average body weight of 9.13±0.03 were allocated to the following experimentally treatments: control diet without AFB1 (normal compound feed for weaned pigs); contaminated diet with 320 mg kg-1 AFB1; GSM diet (compound feed plus 8% grape seed meal) and AFB1+GSM diet (320 mg kg-1 AFB1 contaminated feed plus 8% grape seed meal). Pigs fed AFB1 diet had altered performance, body weight decreasing with 25.1% (b.w.: 17.17 kg for AFB1 vs 22.92 kg for control). Exposure of piglets to AFB1 contaminated diet caused liver oxidative stress as well as liver histological damage, manly characterized by inflammatory infiltrate, fibrosis and parenchyma cells vacuolation when compared to control and GSM meal group. 94.12% of the total analysed genes (34) related to inflammation and immune response was up-regulated. The addition of GSM into the AFB1 diet diminished the gene overexpression and ameliorate histological liver injuries and oxidative stress. The protective effect of GSM diet in diminishing the AFB1 harmful effect was mediated through the decreasing of gene and protein expression of MAPKs and NF-κB signalling overexpressed by AFB1 diet. The inclusion of grape seed by-products in the diet of pigs after weaning might be used as a novel nutritional intervention to reduce aflatoxin toxicity.


Assuntos
Aflatoxina B1/toxicidade , Ração Animal/análise , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fígado/efeitos dos fármacos , Sementes/química , Vitis/química , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Dieta , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Suínos , Desmame
7.
PLoS One ; 15(6): e0235061, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32569334

RESUMO

Aflatoxin B1 aldehyde reductase (AFAR) enzyme activity has been associated to a higher resistance to the aflatoxin B1 (AFB1) toxicity in ethoxyquin-fed rats. However, no studies about AFAR activity and its relationship with tolerance to AFB1 have been conducted in poultry. To determine the role of AFAR in poultry tolerance, the hepatic in vitro enzymatic activity of AFAR was investigated in liver cytosol from four commercial poultry species (chicken, quail, turkey and duck). Specifically, the kinetic parameters Vmax, Km and intrinsic clearance (CLint) were determined for AFB1 dialdehyde reductase (AFB1-monoalcohol production) and AFB1 monoalcohol reductase (AFB1-dialcohol production). In all cases, AFB1 monoalcohol reductase activity saturated at the highest aflatoxin B1 dialdehyde concentration tested (66.4 µM), whereas AFB1 dialdehyde reductase did not. Both activities were highly and significantly correlated and therefore are most likely catalyzed by the same AFAR enzyme. However, it appears that production of the AFB1 monoalcohol is favored over the AFB1 dialcohol. The production of alcohols from aflatoxin dialdehyde showed the highest enzymatic efficiency (highest CLint value) in chickens, a species resistant to AFB1; however, it was also high in the turkey, a species with intermediate sensitivity; further, CLint values were lowest in another tolerant species (quail) and in the most sensitive poultry species (the duck). These results suggest that AFAR activity is related to resistance to the acute toxic effects of AFB1 only in chickens and ducks. Genetic selection of ducks for high AFAR activity could be a means to control aflatoxin sensitivity in this poultry species.


Assuntos
Aflatoxina B1/análogos & derivados , Aldeído Redutase/metabolismo , Aves Domésticas/metabolismo , Aflatoxina B1/química , Aflatoxina B1/toxicidade , Animais , Feminino , Cinética , Masculino
8.
Toxicon ; 184: 152-157, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32531289

RESUMO

Aflatoxicosis is one of the threats that cause severe mortalities in fish farms. The dietary functional additives are a friendly approach attributed to beneficial effects on aquatic animals. The study aimed at evaluating the impact of Spirulina platensis (SP) on the biochemical indices and antioxidative function of Nile tilapia (Oreochromis niloticus) intoxicated with aflatoxin B1 (AFB1). A control diet and 3 test diets were enriched with 0% SP/0 mg AFB1/kg (control), 1% SP (SP), 2.5 mg AFB1/kg diet (AFB1), and 1% SP+2.5 mg AFB1/kg diet (SP/AFB1). The diets were supplied to three aquaria for each group twice daily at the rate of 2.5% for 30 days. The blood alanine transaminase (ALT), alkaline phosphatase (ALP), and aspartate transaminase (AST) were significantly increased by AFB1 toxicity with regards to fish fed the control and SP diets (P < 0.05). The inclusion of SP in the diet of tilapia intoxicated with AFB1 lowered the levels of ALT, AST, and ALP in comparison to fish contaminated with AFB1 without SP (P < 0.05). The total blood protein and albumin were decreased in fish contaminated with AFB1 (P < 0.05); however, the dietary SP resulted in improving the blood protein and albumin with similar levels with the control and SP diets. The urea and creatinine were increased in tilapia fed AFB1 diet without SP (P < 0.05); however, the inclusion of SP reduced the levels of urea and creatinine with similar levels with the control and SP diets. The antioxidative capacity of Nile tilapia fed SP and contaminated with AFB1 is expressed by superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) concentration. The activities of SOD and GSH were decreased by AFB1 (P < 0.05); however, dietary SP increased the SOD and GSH in fish fed AFB1. On the other hand, the concentration of MDA was increased in tilapia fed AFB1 (P < 0.05); however, SP decreased the level of MDA in fish fed AFB1. In conclusion, the application of SP in the aquafeed seems to be an innovative approach to relieve the toxic influences of AFB1 on aquatic animals.


Assuntos
Aflatoxina B1/toxicidade , Ciclídeos/fisiologia , Venenos/toxicidade , Spirulina/fisiologia , Alanina Transaminase/metabolismo , Ração Animal , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/metabolismo , Catalase/metabolismo , Creatinina/metabolismo , Dieta , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Malondialdeído/metabolismo , Estresse Oxidativo , Superóxido Dismutase/metabolismo
9.
Toxicon ; 181: 57-68, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32353570

RESUMO

This study aimed to identify the bioactive compounds of the ethyl acetate extract of Aspergillus niger SH2-EGY using GC-MS and to evaluate their protective role against aflatoxin B1 (AFB1)-induced oxidative stress, genotoxicity and cytotoxicity in rats. Six groups of male Sprague-Dawley rats were treated orally for 4 weeks included the control group, AFB1-treated group (80 µg/kg b.w); fungal extract (FE)-treated groups at low (140) or high dose (280) mg/kg b.w and the groups treated with AFB1 plus FE at the two tested doses. The GC-MS analysis identified 26 compounds. The major compounds found were 1,2,3,4,6-Penta-trimethylsilyl Glucopyranose, Fmoc-L-3-(2-Naphthyl)-alanine, D-(-)-Fructopyranose, pentakis (trimethylsilyl) ether, bis (2-ethylhexyl) phthalate, trimethylsilyl ether-glucitol, and octadecanamide, N-(2- methylpropyl)-N-nitroso. The in vivo results showed that AFB1 significantly increased serum ALT, AST, creatinine, uric acid, urea, cholesterol, triglycerides, LDL, carcinoembryonic antigen, alpha-fetoprotein, interleukin-6, Malondialdehyde, nitric oxide, Bax, caspase-3 and P53 mRNA expression, chromosomal aberrations and DNA fragmentation. It decreased serum TP, albumin, HDL, Bcl-2 mRNA expression, hepatic and renal TAC, SOD and GPx content and induced histological changes in the liver and kidney. FE prevented these disturbances in a dosage-dependent manner. It could be concluded that A. niger SH2-EGY extract is safe a promising agent for pharmaceutical and food industries.


Assuntos
Aflatoxina B1/toxicidade , Antioxidantes/uso terapêutico , Aspergillus niger , Animais , Fragmentação do DNA/efeitos dos fármacos , Inativação Metabólica/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
10.
Biomed Environ Sci ; 33(4): 238-247, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32438961

RESUMO

Objective: This study aimed to explore the protective effect of procyanidin B2 (PCB2) on acute liver injury induced by aflatoxin B 1 (AFB 1) in rats. Methods: Forty Sprague Dawley rats were randomly divided into control, AFB 1, AFB 1 + PCB2, and PCB2 groups. The latter two groups were administrated PCB2 intragastrically (30 mg/kg body weight) for 7 d, whereas the control and AFB 1 groups were given the same dose of double distilled water intragastrically. On the sixth day of treatment, the AFB 1 and AFB 1 + PCB2 groups were intraperitoneally injected with AFB 1 (2 mg/kg). The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide (DMSO). On the eighth day, all rats were euthanized: serum and liver tissue were isolated for further examination. Hepatic histological features were assessed by hematoxylin and eosin-stained sections. Weight, organ coefficient (liver, spleen, and kidney), liver function (serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin), oxidative index (catalase, glutathione, superoxide dismutase, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine), inflammation factor [hepatic interleukin-6 (IL-6) mRNA expression and serum IL-6], and bcl-2/bax ratio were measured. Results: AFB 1 significantly caused hepatic histopathological damage, abnormal liver function, oxidative stress, inflammation, and bcl-2/bax ratio reduction compared with DMSO-treated controls. Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB 1. Conclusion: Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB 1.


Assuntos
Aflatoxina B1/toxicidade , Biflavonoides/farmacologia , Catequina/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Venenos/toxicidade , Proantocianidinas/farmacologia , Substâncias Protetoras/farmacologia , Animais , Biflavonoides/administração & dosagem , Catequina/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Masculino , Proantocianidinas/administração & dosagem , Substâncias Protetoras/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
11.
Ecotoxicol Environ Saf ; 194: 110420, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32151861

RESUMO

In order to alleviate toxic effects of aflatoxins B1 (AFB1) and zearalenone (ZEA) on broiler production performance and gut microbiota, three kinds of compound probiotics (CP) were selected. The optimal ratios of Bacillus subtilis, Lactobacillus casei and Candida utilis in broiler diets were 7, 5 and 6 log CFU/g for ZEA biodegradation (CP1); 6, 7 and 7 log CFU/g for AFB1 biodegradation (CP2); 7, 6 and 7 log CFU/g for ZEA + AFB1 biodegradation (CP3). A total of 350 1-day-old Ross broilers were randomly divided into 7 groups. Group A was the basal diet, group B-G contained ZEA, AFB1, ZEA + AFB1, ZEA + CP1, AFB1+CP2, ZEA + AFB1+CP3, respectively. The experiment showed that AFB1 or AFB1+ZEA significantly decreased broiler production performance, damaged liver and jejunum, increased mycotoxin residues in broiler body; however, three kinds of compound probiotics additions could alleviate mycotoxin negative effects on the above parameters (p < 0.05). The gut microbiota analysis indicated that AFB1+ZEA increased jejunal microbial richness, but which were decreased to almost the same level as the control group by CP3 addition. CP3 addition significantly increased jejunal Firmicutes and Lactobacillus aviarius abundances. The correlative analysis showed that gut Lactobacillus aviarius abundance was positively correlated with average daily gain (ADG) of broilers (p < 0.05), while AFB1+ZEA addition decreased its relative abundance, indicating that CP3 addition increased broiler growth by increasing Lactobacillus aviarius abundance. AFB1 and ZEA residues in broiler body were negatively correlated with the gut beneficial bacterial abundances (p < 0.01), but positively correlated with the potentially harmful bacterial abundances (p < 0.05), which inferred that CP3 addition could decrease mycotoxin residues through positively regulating gut relative bacterial abundances. In conclusion, compound probiotics could keep gut microbiota stable, degrade mycotoxins, alleviate histological lesions, increase production performance and reduce mycotoxin toxicity for broilers.


Assuntos
Aflatoxina B1/toxicidade , Galinhas/crescimento & desenvolvimento , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/farmacologia , Zearalenona/toxicidade , Ração Animal/análise , Ração Animal/microbiologia , Animais , Bacillus subtilis/isolamento & purificação , Galinhas/metabolismo , Dieta , Suplementos Nutricionais , Firmicutes/isolamento & purificação , Distribuição Aleatória
12.
Sci Rep ; 10(1): 5508, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-32218462

RESUMO

A study was conducted to determine the cytosolic in vitro hepatic enzymatic kinetic parameters Vmax, KM, and intrinsic clearance (CLint) for aflatoxin B1 (AFB1) reductase [aflatoxicol (AFL) production] and AFL dehydrogenase (AFB1 production) in four commercial poultry species (chicken, quail, turkey and duck). Large differences were found in AFB1 reductase activity, being the chicken the most efficient producer of AFL (highest CLint value). Oxidation of AFL to AFB1 showed only slight differences among the different poultry species. On average all species produced AFB1 from AFL at a similar rate, except for the turkey which produced AFB1 from AFL at a significantly lower rate than chickens and quail, but not ducks. Although the turkey and duck showed differences in AFL oxidation Vmax and KM parameters, their CLint values did not differ significantly. The ratio AFB1 reductase/AFL dehydrogenase enzyme activity was inversely related to the known in vivo sensitivity to AFB1 being highest for the chicken, lowest for the duck and intermediate for turkeys and quail. Since there is no evidence that AFL is a toxic metabolite of AFB1, these results suggest that AFL production is a detoxication reaction in poultry. Conversion of AFB1 to AFL prevents the formation of the AFB1-8,9-exo-epoxide which, upon conversion to AFB1-dihydrodiol, is considered to be the metabolite responsible for the acute toxic effects of AFB1.


Assuntos
Aflatoxina B1/farmacocinética , Aflatoxina B1/toxicidade , Aflatoxinas/biossíntese , Fígado/efeitos dos fármacos , Fígado/metabolismo , Animais , Carcinógenos/farmacocinética , Carcinógenos/toxicidade , Galinhas , Citosol/metabolismo , Resistência a Medicamentos , Patos , Inativação Metabólica , Aves Domésticas , Codorniz , Perus
13.
Oxid Med Cell Longev ; 2020: 9316751, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104544

RESUMO

The current study was carried out to evaluate the ameliorative effect of fucoidan against aflatoxicosis-induced hepatorenal toxicity in streptozotocin-induced diabetic rats. Sixty-four Wister albino male rats were randomly assigned into eight groups (8 rats each) that received normal saline, fucoidan (FUC) at 100 mg/kg/day orally for 4 weeks, streptozotocin (STZ) at 50 mg/kg/i.p. single dose, STZ plus FUC, aflatoxin B1 (AFB1) at 50 µg/kg/i.p. after one month of the beginning of the experiment for 2 weeks, AFB1 plus FUC, STZ plus AFB1, or STZ plus AFB1 and FUC. Injection of rats with STZ induced hyperglycemia. Rats with STZ-induced diabetes, with or without AFB1 intoxication, had significantly elevated activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, and levels of serum urea, creatinine, cholesterol, 8-oxo-2'-deoxyguanosine, interleukin-1ß, interleukin-6, and tumor necrosis factor-α. In addition, these rats exhibited increased lipid peroxidation and reduced glutathione concentration and activities of superoxide dismutase, catalase, and glutathione peroxidase enzymes in the hepatic and renal tissues. In contrast, administration of FUC to diabetic rats, with or without AFB1 intoxication, ameliorated the altered serum parameters, reduced oxidative stress, DNA damage, and inflammatory biomarkers, and enhanced the antioxidant defense system in the hepatic and renal tissues. These results indicated that FUC ameliorated diabetes and AFB1-induced hepatorenal injuries through alleviating oxidative stress, DNA damage, and inflammation.


Assuntos
Aflatoxina B1/toxicidade , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Polissacarídeos/uso terapêutico , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Dano ao DNA/efeitos dos fármacos , Glutationa/metabolismo , Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Estreptozocina/toxicidade , Superóxido Dismutase/metabolismo
14.
Res Vet Sci ; 129: 103-108, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31954314

RESUMO

To evaluate the protective role of lycopene (LYC) against aflatoxin B1 (AFB1)-induced erythrocyte dysfunction and oxidative stress, male kunming mice were treated with LYC (5 mg/kg) and/or AFB1 (0.75 mg/kg) by intragastric administration for 30 d. Hematological indices were detected to assess erythrocyte function. The erythrocytes C3b receptor rate (E-C3bRR) and erythrocytes C3b immune complex rosette rate (E-ICRR) were detected to assess erythrocyte immune function. Hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents and superoxide dismutase (SOD) and catalase (CAT) activities were determined to evaluate erythrocyte oxidative stress. The results showed that LYC administration significantly relieved AFB1-induced erythrocyte dysfunction by increasing the levels of red blood cell count (RBC), hemoglobin (HGB) and hematocrit (HCT), as well as reducing red blood cell volume distribution width (RDW) level, while the levels of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and mean platelet volume (MPV) had no significant differences among the four groups. Besides, LYC ameliorated AFB1-induced erythrocyte immune dysfunction by increasing E-C3bRR and decreasing E-ICRR. Furthermore, LYC also alleviated AFB1-induced erythrocyte oxidative stress by decreasing H2O2 and MDA contents and increasing SOD and CAT activities. These results indicated that LYC protected against AFB1-induced erythrocyte dysfunction and oxidative stress in mice. The findings could lead a possible therapeutics for the management of AFB1-induced erythrocyte toxicity.


Assuntos
Aflatoxina B1/toxicidade , Antioxidantes/farmacologia , Eritrócitos/efeitos dos fármacos , Licopeno/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Índices de Eritrócitos , Hematócrito , Peróxido de Hidrogênio , Masculino , Malondialdeído , Camundongos
15.
Environ Mol Mutagen ; 61(2): 224-234, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31112310

RESUMO

The accessibility of reactive metabolites to test cells is critical for a genotoxic response. However, sulfo-conjugates formed outside may not readily enter cells, and some metabolites formed by cytochromes P450 (CYPs) may not endure transport. This topic was addressed in the present study, using V79 cells engineered for human CYPs and/or a sulfotransferase (SULT). First, 1-methylpyrene, 1-hydroxymethylpyrene, benzo[a]pyrene, and aflatoxin B1 significantly induced micronuclei in V79-hCYP1A2-hSULT1A1, V79-hSULT1A1, V79-hCYP1A1, and V79-hCYP1A2 cells, respectively. Subsequently, we used these cell lines as external activating systems in various experimental settings in combination with V79-derived target cells lacking critical enzymes. 1-Methylpyrene (activated by CYPs and SULTs sequentially) showed an activity similar to that in V79-hCYP1A2-hSULT1A1 cells, in each following model: a mixed V79-hCYP1A2:V79-hSULT1A1 (1:1) culture, exposure of V79-hCYP1A2 to 1-methylpyrene followed by transfer of medium to V79-hSULT1A1 target cells, and V79-hSULT1A1 communicating with V79-hCYP1A2 through 0.4-µm pores and over a 1-mm distance in a unique transwell system. These results suggest ready transfer of 1-hydroxymethylpyrene formed in V79-hCYP1A2 to V79-hSULT1A1 for further activation. In the last two models, with V79-hSULT1A1 for activation and V79-Mz as target, 1-hydroxymethylpyrene induced micronuclei mildly, suggesting limited intercellular transfer of the ultimate genotoxicant, 1-sulfooxymethylpyrene. Benzo[a]pyrene induced micronuclei in V79-Mz communicating with V79-hCYP1A1 via porous membranes, whereas aflatoxin B1 was inactive in V79-Mz communicating with V79-hCYP1A2. Our results suggest that the sulfo-conjugate tested may have difficulty entering cells for a genotoxic effect, and the reactive metabolite of aflatoxin B1, unlike that of benzo[a]pyrene, could not travel an adequate distance to enter cells. Environ. Mol. Mutagen. 61:224-234, 2020. © 2019 Wiley Periodicals, Inc.


Assuntos
Aflatoxina B1/toxicidade , Benzo(a)pireno/toxicidade , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Mutagênicos/toxicidade , Pirenos/toxicidade , Aflatoxina B1/metabolismo , Animais , Arilsulfotransferase/metabolismo , Benzo(a)pireno/metabolismo , Linhagem Celular , Cricetinae , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos , Testes para Micronúcleos , Mutagênicos/metabolismo , Pirenos/metabolismo
16.
Food Chem Toxicol ; 135: 110768, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31479712

RESUMO

Stem bark of Erythrina latissima E. Mey (Leguminosae) contains a wide range of prenylated flavonoids able to counteract the genotoxic properties of aflatoxin B1 (AFB1). Thus, the hypothesis was raised that E. latissima stem bark extracts (ELBE) may counteract the in vivo hepatotoxic effects of aflatoxins, contaminants in food and feed. An HPLC-DAD method was developed and validated to determine the level of flavonoid aglycones (11.82%) and glycosides (16.17%). ADME, pharmacokinetic and drug-likeness assessment of major flavonoids of ELBE, using the web tool SwissADME, showed good oral bioavailability. The protective effect of ELBE against AFB1 induced genotoxicity in the Vitotox assay after metabolic activation was confirmed (IC50 of 44.32 µg/ml), followed by evaluation of its inhibitory effect on hepatotoxicity in rats induced by the same agent. Male Wistar rats were orally treated with ELBE (20 mg/kg, 50 mg/kg and 100 mg/kg) or curcumin (500 mg/kg) combined with piperine (20 mg/kg) - positive control, for 8 days prior to AFB1 exposure (1 mg/kg). The ELBE group showed a decreased activity of ALP and γ-GT compared to the AFB1 group. Histopathological examination of the liver demonstrated ameliorative effects of ELBE. Thus, ELBE could have a protective effect against hepatotoxins such as AFB1.


Assuntos
Aflatoxina B1/toxicidade , Antimutagênicos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Erythrina/química , Casca de Planta/química , Extratos Vegetais/farmacologia , Caules de Planta/química , Animais , Antimutagênicos/farmacocinética , Cromatografia Líquida de Alta Pressão , Simulação por Computador , Flavonoides/análise , Masculino , Extratos Vegetais/química , Ratos , Ratos Wistar , Reprodutibilidade dos Testes
17.
Artigo em Inglês | MEDLINE | ID: mdl-31493584

RESUMO

Aflatoxin B1 (AFB1) is one of the most important mycotoxins due to its hepatotoxic and carcinogenic effects on animals. The effect of dietary supplementation with vegetable choline (VC) at 400, 800, and 1200 mg/kg against the deleterious effects of AFB1 (2 ppm/kg diet) in the liver of Nile tilapia (Oreochromis niloticus) was studied. The experimental period was 81 days, and the diet with VC was offered to the fish for 60 days prior to challenge with AFB1. Diets with AFB1 were tested in three replications and animals were analyzed at days 14 and 21 of dietary intake. The addition of VC to tilapia diet increased body weight (days 30 and 60 pre-challenge and day 21 post-challenge). The group fed aflatoxin-contaminated diet presented significantly reduced antioxidant enzymes and increased reactive oxygen species (ROS) levels, thiobarbituric acid reactive species (TBARS) levels, and protein carbonyl (PC) content in the liver. Dietary supplementation with VC at 800 and 1200 mg/kg demonstrated a significant protective effect, avoiding the increase of ROS, TBARS, and PC levels in the liver of tilapia from the aflatoxin contaminated groups. Thus, dietary VC supplementation may be used in tilapia to increase antioxidant status and reduce the negative effects caused by AFB1 toxicity. Based on the findings, it is recommended to use VC as a food supplement for Nile tilapia in order to avoid AFB1 toxication. In addition, decreased aflatoxin toxicity can be attributed to the VC antioxidant property.


Assuntos
Aflatoxina B1/toxicidade , Ração Animal/análise , Colina/farmacologia , Ciclídeos , Doenças dos Peixes/induzido quimicamente , Contaminação de Alimentos , Aflatoxina B1/administração & dosagem , Animais , Catalase/genética , Catalase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/veterinária , Colina/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Doenças dos Peixes/tratamento farmacológico , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
18.
Mycotoxin Res ; 36(1): 31-39, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31297722

RESUMO

The effect of dietary aflatoxin B1 (AFB1) and Salmonella Enteritidis infection on intestinal permeability was investigated. Two hundred 1-day-old male Ross 308 broiler chickens were randomly divided into 4 treatments of 5 replicates each (10 birds per replicate), which were fed ad libitum for 3 weeks with the following treatments: control, chickens fed an AFB1-free diet; AF, chickens fed an AFB1-contaminated diet at 470 ng/g; SE, chickens fed an AFB1-free diet and challenged with 108 cfu of S. Enteritidis per bird at 18 days old; AF + SE, chickens fed an AFB1-contaminated diet and challenged with 108 cfu of S. Enteritidis per bird at 18 days old. At day 21 of age, chicks received an oral gavage dose of fluorescein isothiocyanate dextran (FITC-dextran) to evaluate gastrointestinal leakage. Blood and intestinal samples were collected to evaluate serum biochemistry and total intestinal IgA secretion, respectively. Liver tissues were aseptically collected to assess bacterial invasiveness and for histomorphological studies. The results showed that chickens receiving AFB1 presented a significant increment (up to 2.4-fold) in serum FITC-dextran concentration (p < 0.05). Nevertheless, S. Enteritidis infection had no additional effect on gastrointestinal leakage. Furthermore, the ingestion of AFB1 had no impact on the invasive potential of S. Enteritidis. These results suggest that moderate-dose AFB1 adversely affects intestinal barrier function resulting in increased gut permeability in broiler chickens.


Assuntos
Aflatoxina B1 , Intestinos/patologia , Permeabilidade/efeitos dos fármacos , Salmonella enteritidis/patogenicidade , Aflatoxina B1/administração & dosagem , Aflatoxina B1/efeitos adversos , Aflatoxina B1/toxicidade , Ração Animal/análise , Animais , Galinhas , Dieta/veterinária , Fígado/efeitos dos fármacos , Fígado/microbiologia , Fígado/patologia , Doenças das Aves Domésticas , Salmonelose Animal
19.
Ecotoxicol Environ Saf ; 187: 109712, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31654867

RESUMO

Mycotoxicosis is the second most important problem faced by the Pakistan poultry industry, after high feed prices. The present experimental study was designed to investigate the toxicopathological effects of aflatoxin B1 (AFB1) in commercial broiler chicks and its amelioration with locally produced mycotoxin binder. Total of 125 broiler chicks was divided into five equal groups (A-E). Group A served as negative control, group B (300 µg AFB1/kg feed) as positive control, group C (300 µg AFB1/kg + Local Mycotoxin Binder (LMB), 1 g/kg feed), group D (300 µg AFB1/kg + 2 g LMB/kg feed), and group E (300 µg AFB1/kg + Commercial Mycotoxin Binder (CMB), 2 g/kg of feed). Parameters studied included mortality, feed intake, bodyweights, absolute and relative organ weights, and gross and microscopic lesions in visceral organs. Clinical signs including alertness, fecal consistency, and feather shine were significantly lower in group B compared with control group A. The feed intake of 2 g/kg LMB treated group was significantly higher than that of the positive control group B. Also mean bodyweights of group D birds was higher than that of group B birds indicating an ameliorative effect of LMB. Histopathological results showed that moldy feed produced necrotic changes in the liver and kidneys in group B birds. However, in group D and E birds, the hepatic and renal parenchyma was normal, showing a protective effect of LMB. In the present study, a higher dose of LMB (2 g/kg) in group D showed higher bodyweights and feed intake. In group D, birds hepatic and renal parenchyma was also normal. The results suggested that local mycotoxin binder ameliorated the toxicopathological effects of AFB1 in mortality, feed intake, bodyweights, organ weights and, gross and microscopic lesions in visceral organs. These ameliorative effects of LMB were dose-dependent. The results of the present study concluded that AFB1 intoxication leads to decrease in bodyweights, feed intake in dose-related manner. The mortality was also dose-dependent. Gross and microscopic changes in the aflatoxin groups were more pronounced, however, all these deleterious effects were ameliorated in higher dose of LMB (group D) and CMB (group E). In group C, these deleterious effects were partially ameliorated. Local mycotoxin binder is an economical solution for aflatoxicosis problem, making poultry production more cost-effective.


Assuntos
Aflatoxina B1/toxicidade , Ração Animal/análise , Contaminação de Alimentos/prevenção & controle , Micotoxicose/prevenção & controle , Doenças das Aves Domésticas/prevenção & controle , Aflatoxina B1/química , Animais , Bentonita/administração & dosagem , Bentonita/química , Galinhas , Contaminação de Alimentos/análise , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Micotoxicose/veterinária , Tamanho do Órgão , Paquistão , Saccharomyces cerevisiae/química
20.
Toxicol Lett ; 319: 155-159, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31706005

RESUMO

Novel HepG2 cell clones 1A2 C2 and 1A2 C7 were independently generated by lentiviral transduction to functionally overexpress cytochrome P450 1A2 (CYP1A2). We found similar and stable CYP1A2 transcript and protein levels in both cell clones leading to specific enzyme activities of about 370 pmol paracetamol x min-1 x mg-1 protein analyzed by phenacetin conversion. Both clones showed dramatically increased sensitivity to the hepatotoxic compound aflatoxin B1 (EC50 < 100 nM) when compared to parental HepG2 cells (EC50∼5 µM). Thus, newly established cell lines are an appropriate tool to study metabolism and toxicity of substances depending on conversion by CYP1A2.


Assuntos
Citocromo P-450 CYP1A2/genética , Vetores Genéticos/genética , Hepatoblastoma/enzimologia , Hepatoblastoma/genética , Lentivirus/genética , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/genética , Aflatoxina B1/toxicidade , Linhagem Celular Tumoral , Citocromo P-450 CYP1A2/biossíntese , Impressões Digitais de DNA/métodos , Humanos , Fígado/metabolismo , Mycoplasma/química , Fenacetina/farmacocinética , Plasmídeos/genética
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