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1.
Environ Sci Pollut Res Int ; 25(15): 15102-15110, 2018 May.
Article in English | MEDLINE | ID: mdl-29557044

ABSTRACT

Deltamethrin is one of the most commonly used pyrethroids in the world, and it has a high toxic potential, mainly on aquatic organism. Thus, the purpose of this study was to evaluate LC50 values of deltamethrin on tambaqui (Colossoma macropomum) fingerlings and to investigate genotoxic effects and histopathological responses. Fish were exposed to different concentrations of deltamethrin (0, 6.16 × 10-3; 6.44 × 10-2; 1.34 × 10-1, and 1.93 × 10-1 mg L-1) for 96 h. In addition, a genotoxicity analysis was carried out on peripheral blood erythrocytes and histopathological changes were classified by the severity degree of damage and organ functioning. The 96 h LC50 value for tambaqui was estimated at 5.56 × 10-2 mg L-1 using a static test system. Nuclear abnormalities in exposed fish included micronuclei, blebbed, notched, 8-shaped, and binucleated nuclei forms. Deltamethrin significantly induced a notched nucleus compared to other abnormalities. A histopathological examination showed hepatic lesions and gill damage. Deltamethrin was found to be highly toxic; it induced genotoxicity and caused liver and gill inflammation in tambaqui.


Subject(s)
Cell Nucleus/drug effects , Erythrocytes/drug effects , Fishes/genetics , Gills/drug effects , Liver/drug effects , Nitriles/toxicity , Pyrethrins/toxicity , Water Pollutants, Chemical/toxicity , Animals , Cell Nucleus/ultrastructure , DNA Damage , Erythrocytes/ultrastructure , Fishes/blood , Gills/pathology , Lethal Dose 50 , Liver/pathology , Toxicity Tests, Acute
2.
Fungal Biol ; 120(8): 1050-1063, 2016 08.
Article in English | MEDLINE | ID: mdl-27521636

ABSTRACT

Fungi have highly active secondary metabolic pathways which enable them to produce a wealth of sesquiterpenoids that are bioactive. One example is Δ6-protoilludene, the precursor to the cytotoxic illudins, which are pharmaceutically relevant as anticancer therapeutics. To date, this valuable sesquiterpene has only been identified in members of the fungal division Basidiomycota. To explore the untapped potential of fungi belonging to the division Ascomycota in producing Δ6-protoilludene, we isolated a fungal endophyte Diaporthe sp. BR109 and show that it produces a diversity of terpenoids including Δ6-protoilludene. Using a genome sequencing and mining approach 17 putative novel sesquiterpene synthases were identified in Diaporthe sp. BR109. A phylogenetic approach was used to predict which gene encodes Δ6-protoilludene synthase, which was then confirmed experimentally. These analyses reveal that the sesquiterpene synthase and its putative sesquiterpene scaffold modifying cytochrome P450(s) may have been acquired by inter-phylum horizontal gene transfer from Basidiomycota to Ascomycota. Bioinformatic analyses indicate that inter-phylum transfer of these minimal sequiterpenoid secondary metabolic pathways may have occurred in other fungi. This work provides insights into the evolution of fungal sesquiterpenoid secondary metabolic pathways in the production of pharmaceutically relevant bioactive natural products.


Subject(s)
Ascomycota/genetics , Ascomycota/metabolism , Biosynthetic Pathways , Gene Transfer, Horizontal , Genome, Fungal , Sesquiterpenes/metabolism , Antineoplastic Agents/metabolism , Ascomycota/isolation & purification , Computational Biology , Endophytes/genetics , Endophytes/isolation & purification , Endophytes/metabolism , Evolution, Molecular , Sequence Analysis, DNA , Sequence Homology
3.
Biometals ; 28(4): 783-9, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25913293

ABSTRACT

Over a thousand extracts were tested for phenotypic effects in developing zebrafish embryos to identify bioactive molecules produced by endophytic fungi. One extract isolated from Fusarium sp., a widely distributed fungal genus found in soil and often associated with plants, induced an undulated notochord in developing zebrafish embryos. The active compound was isolated and identified as fusaric acid. Previous literature has shown this phenotype to be associated with copper chelation from the active site of lysyl oxidase, but the ability of fusaric acid to bind copper ions has not been well described. Isothermal titration calorimetry revealed that fusaric acid is a modest copper chelator with a binding constant of 4.4 × 10(5) M(-1). These results shed light on the toxicity of fusaric acid and the potential teratogenic effects of consuming plants infected with Fusarium sp.


Subject(s)
Chelating Agents/pharmacology , Copper/metabolism , Fusaric Acid/pharmacology , Notochord/abnormalities , Notochord/drug effects , Zebrafish/abnormalities , Zebrafish/metabolism , Animals , Calorimetry , Chelating Agents/chemistry , Chelating Agents/isolation & purification , Fusaric Acid/chemistry , Fusaric Acid/isolation & purification , Fusarium/chemistry , Molecular Structure
4.
Oxid Med Cell Longev ; 2012: 697541, 2012.
Article in English | MEDLINE | ID: mdl-23251721

ABSTRACT

This work was designed to study MCT effect in histopathological analysis of hippocampus (HC) and parahippocampal cortex (PHC) and in oxidative stress (OS) parameters in brain areas such as hippocampus (HC), prefrontal cortex (PFC), and striatum (ST). Swiss mice (25-30 g) were administered a single i.p. dose of MCT (5, 50, or 100 mg/kg) or 4% Tween 80 in saline (control group). After 30 minutes, the animals were sacrificed by decapitation and the brain areas (HC, PHC, PFC, or ST) were removed for histopathological analysis or dissected and homogenized for measurement of OS parameters (lipid peroxidation, nitrite, and catalase) by spectrophotometry. Histological evaluation of brain structures of rats treated with MCT (50 and 100 mg/kg) revealed lesions in the hippocampus and parahippocampal cortex compared to control. Lipid peroxidation was evident in all brain areas after administration of MCT. Nitrite/nitrate content decreased in all doses administered in HC, PFC, and ST. Catalase activity was increased in the MCT group only in HC. In conclusion, monocrotaline caused cell lesions in the hippocampus and parahippocampal cortex regions and produced oxidative stress in the HC, PFC, and ST in mice. These findings may contribute to the neurological effects associated with this compound.


Subject(s)
Brain/drug effects , Brain/pathology , Monocrotaline/toxicity , Oxidants/toxicity , Animals , Brain/enzymology , Caspase 3/metabolism , Catalase/metabolism , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Corpus Striatum/pathology , Hippocampus/drug effects , Hippocampus/enzymology , Hippocampus/pathology , Immunohistochemistry , Lipid Peroxidation/drug effects , Male , Mice , Monocrotaline/administration & dosage , Nitrites/metabolism , Oxidative Stress/drug effects , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Prefrontal Cortex/pathology , Rats , Thiobarbituric Acid Reactive Substances/metabolism
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