Multiple lethal effects induced by a benzimidazole anthelmintic in the anterior intestine of the nematode Haemonchus contortus

Jasmer, Douglas P.; Yao, Chaoqun; Rehman, Abdur; Johnson, Sandra S.

doi:10.1016/s0166-6851(99)00169-3

Cited by 55 publications

(45 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…41 Os benzimidazóis são medicamentos veterinários com ação anti-helmíntica por meio da inibição da formação de microtúbulos do parasito, importantes na formação do fuso mitótico, motilidade e secreção celular, absorção de nutrientes e transporte celular. 42 A estrutura dos benzimidazóis é caracterizada por um anel benzênico condensado a um grupo imidazol (Quadro 1).…”

Section: Antiparasitáriosunclassified

Resíduos de medicamentos veterinários em leite e ovos

Pacheco-Silva¹,

Souza²,

Caldas³

2014

Quím. Nova

View full text Add to dashboard Cite

VETERINARY DRUG RESIDUES IN MILK AND EGGS. The use of veterinary drugs in food producing animals may result in the presence of residues in foods, including milk and eggs. Immunoassay or microbiological tests are used to screen for residues, but chromatographic methods are needed to confirm positive results. In most methods, the sample is extracted with acetonitrile, submitted to clean up or directly analyzed by LC-MS/MS. Results of the Brazilian governmental monitoring programs from 2006 to 2011 have shown that the antiparasitic ivermectin was the drug most frequently found in milk. Residues in eggs are only monitored by one of the programs, and few studies have reported the incidence of veterinary drugs in this matrix in Brazil.Keywords: veterinary drugs; milk; eggs. INTRODUÇÃOMedicamentos são usados na medicina veterinária no tratamento e prevenção de doenças ou como promotores de crescimento. 1,2 Estes compostos compreendem uma variedade de classes químicas com ações terapêuticas diversas, incluindo antibiótica/antimicrobiana, antiparasitária, inseticida, fungicida e sedativa. 3 Os antimicrobianos (b-lactâmicos, aminoglicosídeos e tetraciclinas) e os antiparasitários (avermectinas, piretróides e organofosforados) são os produtos mais comercializados no Paraná para tratamento do rebanho leiteiro. 4 O uso de medicamentos veterinários em animais produtores de alimentos pode deixar resíduos nos alimentos, como carne, leite e ovos, cujos níveis não devem ultrapassar o Limite Máximo de Resíduos (LMR). O LMR é a concentração máxima de resíduo em um alimento de origem animal resultante do uso de um medicamento veterinário (expresso em mg/kg ou µg/kg, em peso fresco) que é recomendado para ser legalmente permitido ou reconhecido como sendo aceitável no alimento. 5 Estes limites são estabelecidos para garantir o uso adequado destes produtos, limitar a exposição e proteger a saúde dos consumidores dos alimentos provenientes de animais tratados. 5 A presença de resíduos em um alimento acima do LMR estabelecido indica que o produto não foi utilizado segundo as boas práticas de uso de medicamentos veterinários (BPMV), ou o uso de um produto não autorizado. 6 O Brasil não estabelece LMR para medicamentos veterinários, adotando aqueles recomendados pelo Mercosul, Codex Alimentarius, União Européia ou Estados Unidos. 7 A exposição humana a resíduos de medicamentos veterinários presentes nos alimentos pode causar efeitos adversos, incluindo reações alérgicas em indivíduos hipersensíveis 8 e câncer. 9,10 Adicionalmente, a exposição a antimicrobianos/antibióticos pode provocar o desenvolvimento de microrganismos resistentes, que dificulta a ação terapêutica destes medicamentos em indivíduos que consumiram alimentos de animais tratados. 11,12 Resíduos de medicamentos veterinários no leite podem também causar problemas tecnológicos nos processos de fermentação dos laticínios. 13,14 No Brasil, há dois programas nacionais que monitoram a presença de resíduos de medicamentos veterinários em produtos de origem animal. O Plano Nacional...

show abstract

Section: Antiparasitáriosunclassified

Resíduos de medicamentos veterinários em leite e ovos

Pacheco-Silva¹,

Souza²,

Caldas³

2014

Quím. Nova

View full text Add to dashboard Cite

show abstract

“…The pattern of DNA fragmentation resembled that associated with apoptosis, which can be initiated by caspase and noncaspase cysteine proteases (11,12), while CED-3 is a prominent nematode caspase (13). Both tissue disintegration and DNA fragmentation was associated with inhibited transport of secretory vesicles and subsequent cytoplasmic dispersal of vesicle contents in anterior intestinal cells (10). The monoclonal antibody (mAb 42/10.6.1) used to monitor secretory vesicle contents binds to a periodate-sensitive determinant found on numerous intestinal membrane and secretory proteins (14).…”

mentioning

confidence: 86%

“…Initial interest in evaluating caspase substrates arose from the DNA fragmentation that can be induced by fenbendazole in intestinal cell nuclei of this parasite (10). Preliminary experiments at pH 5.0 demonstrated activity against each substrate, with the exception of DEVD (Fig.…”

Section: Peptide Substrate Recognition In H Contortus Intestine and mentioning

confidence: 99%

“…CBLs are also currently considered as vaccine candidates for immune control of parasitic nematodes, including H. contortus (6 -9). Alternatively, digestive proteases may indirectly mediate anthelmintic efficacy involving benzimidazole anthelmintics (10). Following fenbendazole treatment of lambs, anterior intestinal cells of H. contortus undergo fragmentation of nuclear DNA and tissue disintegration (10).…”

mentioning

confidence: 99%

“…Alternatively, digestive proteases may indirectly mediate anthelmintic efficacy involving benzimidazole anthelmintics (10). Following fenbendazole treatment of lambs, anterior intestinal cells of H. contortus undergo fragmentation of nuclear DNA and tissue disintegration (10). The pattern of DNA fragmentation resembled that associated with apoptosis, which can be initiated by caspase and noncaspase cysteine proteases (11,12), while CED-3 is a prominent nematode caspase (13).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Cathepsin B-like Cysteine Proteases Confer Intestinal Cysteine Protease Activity in Haemonchus contortus

Shompole

Jasmer

2001

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Cathepsin B-like cysteine protease genes (cbls) constitute large multigene families in parasitic and nonparasitic nematodes. Although expressed in the intestine of some nematodes, the biological and biochemical functions of the CBL proteins remain unresolved. Di-and tetra-oligopeptides were used as fluorogenic substrates and irreversible/competitive inhibitors to establish CBL functions in the intestine of the parasitic nematode Haemonchus contortus. Cysteine protease activity was detected against diverse substrates including the cathepsin B/L substrate FR, the caspase 1 substrate YVAD, the cathepsin B substrate RR, but not the CED-3 (caspase 3) substrate DEVD. The pH at which maximum activity was detected varied according to substrate and ranged from pH 5.0 to 7.0. Individual CBLs were affinity isolated using FA and YVAD substrates. pH influenced CBL affinity isolation in a substrate-specific manner that paralleled pH effects on individual substrates. N-terminal sequencing identified two isolated CBLs as H. contortus GCP-7 (33 kDa) and AC-4 (37 kDa). N termini of each began at a position consistent with proregion cleavage and protease activation. Isolation of the GCP-7 band by each peptide was preferentially inhibited when competed with a diazomethane-conjugated inhibitor, Z-FA-CHN 2 , demonstrating one functional difference among CBLs and among inhibitors. Substrate-based histological analysis placed CBLs on the intestinal microvilli. Data indicate that CBLs are responsible for cysteine protease activity described from H. contortus intestine. Results also support a role of CBLs in nutrient digestion.

show abstract

Metal‐Ion‐Mediated Tuning of Duplex DNA Binding by Bis(2‐(2‐pyridyl)‐1H‐benzimidazole)

Bhattacharya¹,

Chaudhuri²

2007

Chemistry An Asian Journal

View full text Add to dashboard Cite

Studies of double-stranded-DNA binding have been performed with three isomeric bis(2-(n-pyridyl)-1H-benzimidazole)s (n=2, 3, 4). Like the well-known Hoechst 33258, which is a bisbenzimidazole compound, these three isomers bind to the minor groove of duplex DNA. DNA binding by the three isomers was investigated in the presence of the divalent metal ions Mg(2+), Co(2+), Ni(2+), Cu(2+), and Zn(2+). Ligand-DNA interactions were probed with fluorescence and circular dichroism spectroscopy. These studies revealed that the binding of the 2-pyridyl derivative to DNA is dramatically reduced in the presence of Co(2+), Ni(2+), and Cu(2+) ions and is abolished completely at a ligand/metal-cation ratio of 1:1. Control experiments done with the isomeric 3- and 4-pyridyl derivatives showed that their binding to DNA is unaffected by the aforementioned transition-metal ions. The ability of 2-(2-pyridyl)benzimidazole to chelate metal ions and the conformational changes of the ligand associated with ion chelation probably led to such unusual binding results for the ortho isomer. The addition of ethylenediaminetetraacetic acid (EDTA) reversed the effects completely.

show abstract

Multiple lethal effects induced by a benzimidazole anthelmintic in the anterior intestine of the nematode Haemonchus contortus

Cited by 55 publications

References 27 publications

Resíduos de medicamentos veterinários em leite e ovos

Resíduos de medicamentos veterinários em leite e ovos

Cathepsin B-like Cysteine Proteases Confer Intestinal Cysteine Protease Activity in Haemonchus contortus

Metal‐Ion‐Mediated Tuning of Duplex DNA Binding by Bis(2‐(2‐pyridyl)‐1H‐benzimidazole)

Contact Info

Product

Resources

About