Avaliação da atividade da enzima glutationa-s-transferase da minhoca Eisenia foetida exposta à ivermectina / Evaluation of glutatione-s-transferase enzyme activity of the earthworm Eisenia foetida exposed to ivermectin

Muitos tipos de drogas são usados na medicina veterinária para controlar e melhorar a saúde animal através de tratamentos terapêuticos e profiláticos. A desvantagem desta prática é que os produtos farmacêuticos e seus metabólitos são liberados no ambiente e podem influenciar a fauna do solo através da excreção do esterco ou pela posterior aplicação ao campo agrícola. As avermectinas são vastamente utilizadas na medicina veterinária e na agricultura. Estudos anteriores demonstraram que a ivermectina (IVM), um parasiticida amplamente utilizado, é muito tóxico para diversas espécies de invertebrados não-alvo. Tendo em vista que a IVM é pouco metabolizada, excretada de forma relativamente inalterada e pela escassez de dados sobre a toxicidade aos invertebrados do solo, foram investigados, neste estudo, os efeitos agudos e crônicos deste parasiticida sobre a glutationa-s -transferase (GST) da oligoqueta Eisenia foetida. As minhocas Eisenia foetida foram expostas à concentrações de IVM a 0, 1, 5, 10, 50 e 100 mg kg-1, e as amostras foram tomadas nos dias 7, 14 e 28 para determinação da atividade da GST. Os resultados mostraram que a duração da exposição alterou significativamente os efeitos do parasiticida investigado sobre a atividade de GST. Especificamente, após uma redução inicial, o prolongamento da exposição causou a indução da atividade da GST. Com o aumento da concentração de IVM, as atividades da GST foram inibidas significativamente após 7 dias de exposição. Em particular, o efeito inibitório foi significativo nas concentrações mais elevadas de tratamento (10, 50 e 100 mg kg-1). Por outro lado, aos 14 e 28 dias foram observadas induções na atividade da enzima. A atividade da GST pode ser considerada como parâmetro sensível para avaliar a toxicidade da ivermectina para minhocas.

Many types of drugs are used in veterinary medicine to control and improve animal health through therapeutic and prophylactic treatments. The disadvantage of this practice is that pharmaceuticals and their metabolites are released into the environment and may influence soil fauna through manure excretion and subsequent application to agricultural field. The avermectins are extensively and increasingly used in veterinary medicine and agriculture. Previous studies have shown that ivermectin (IVM), a widely used parasiticide, is very toxic to many non-target invertebrate species. In view of the little metabolism and most of the ivermectin dose given to the animal is excreted, relatively unaltered, primarily in the feces and the scarcity of data on toxicity to soil invertebrates, acute and chronic effects of the parasiticide on the glutatione-s-transferase (GST) of the oligochaete Eisenia foetida were investigated. Earthworms of Eisenia foetida were exposed to IVM at 0, 1, 5, 10, 50 and 100 mg kg-1 concentrations; samples were taken at days 7, 14, and 28 exposure for determination of GST activities. The results showed that duration of the exposure significantly changed the effects of the investigated parasiticide on the GST activity. Namely, after the initial decrease, the prolongation of exposure caused the induction of the GST activity. With increasing IVM concentration, GST activities were inhibited significantly after 7 days of the exposure. In particular, the inhibition effect was significant at the higher treatment levels (10, 50 and 100 mg kg-1). On the other hand, at 14 and 28 days were observed inductions of enzyme activity. GST activity can be regarded as sensitive parameter for evaluating the toxicity of ivermectin to earthworms.

Biodistribution and Postmortem Redistribution of Emamectin Benzoate in Intoxicated Mice / 法医学杂志

OBJECTIVE@#To investigate the lethal blood level, the target organs and tissues, the toxicant storage depots and the postmortem redistribution in mice died of emamectin benzoate poisoning.@*METHODS@#The mice model of emamectin benzoate poisoning was established via intragastric injection. The main poisoning symptoms and the clinical death times of mice were observed and recorded dynamically in the acute poisoning group as well as the sub-acute poisoning death group. The pathological and histomorphological changes of organs and tissues were observed after poisoning death. The biodistribution and postmortem redistribution of emamectin benzoate in the organs and tissues of mice were assayed by the enzyme-linked immunosorbent assay (ELISA) at 0h, 24h, 48h and 72h after death. The lethal blood concentrations and the concentrations of emamectin benzoate were detected by high performance liquid chromatography (HPLC) at different time points after death.@*RESULTS@#The symptoms of nervous and respiratory system were observed within 15-30 min after intragastric injection. The average time of death was (45.8 ± 7.9) min in the acute poisoning group and (8.0 ± 1.4) d in the sub-acute poisoning group, respectively. The range of acute lethal blood level was 447.164 0-524.463 5 mg/L. The pathological changes of the organs and tissues were observed via light microscope and immunofluorescence microscope. The changes of emamectin benzoate content in the blood, heart, liver, spleen, lung, kidney and brain of poisoning mice showed regularity within 72 h after death (P < 0.05).@*CONCLUSION@#The target organs of emamectin benzoate poisoning include heart, liver, kidney, lung, brain and contact position (stomach). The toxicant storage depots are kidney and liver. There is emamectin benzoate postmortem redistribution in mice.

Parâmetros qualitativos da carne de cordeiros submetidosaos modelos de produção orgânico e convencional / Qualitative parameters of lamb meat submitted to organic and conventional production models

Este trabalho objetivou avaliar parâmetros qualitativos da carne, análise sensorial e quantificação de resíduo de drogaveterinária e metais pesados provenientes de 48 cordeiros Ile de France submetidos aos modelos de produção orgânicoe convencional, os quais foram abatidos aos 32 kg de peso corporal. A carne dos cordeiros do modelo orgânico tevemaior teor de amarelo que a dos cordeiros do modelo convencional aos 45 minutos após o abate, sendo que os demaisparâmetros L* e a* não foram afetados, já a cor da carne dos cordeiros 24 horas após o abate, não foi influenciada pelostratamentos. Não houve efeito dos tratamentos no pH e na temperatura aos 45 minutos e 24 horas após o abate, nacapacidade de retenção de água e na força de cisalhamento, enquanto as perdas de peso na cocção foram influenciadaspelos tratamentos. Na carne dos cordeiros criados no modelo orgânico, a maciez subjetiva e a aceitação global foraminferiores quando comparadas às do modelo convencional.Os tratamentos não influenciaram os teores de arsênio,cádmio e chumbo da carne. Constatou-se inexistência do princípio ativo ivermectina na carne proveniente dos modelosde produção orgânico e convencional.

This work aimed to evaluate qualitative parameters of meat, sensorial analysis, ivermecin residue and heavy metalsfrom 48 Ile de France lambs submitted to organic and conventional production models which were slaughtered at 32 kgof body weight. Lamb meat from organic model had larger yellowness w to compawithto conventional mo to 45 minutesafter the slaught anbut L * and a* parameters were not affeced;, however, not eady the color of lamb meat 24 hoursafter the slaugter, not influenced by treatments. There was not effect of treatments in pH and temperatureat 45 minutesand 24 hours after the slaughter, in water holding capacity and in shear force, while the cooking losses were influencedby treatments. In the meat of lambs submitted to organic model, the subjective tenderness and the global acceptancewere lower when compared to convencional model. Treatments didn’t influence arsenic, cadmium and lead meat tenor.Inexistence of ivermectin was verified in meat from organic and conventional production models.

Comparative hematological and histopathological toxicity of two potential bio-insecticides against albino rats

Ivermectin [1.8% E.C] and spinosad [24% SC] are bioinsecticides produced by fermentation of some bacteria species. These compounds were selected to evaluate their haematological and histopathological toxicities against albino rats. The tested compounds were orally administrated to rats at 1/10 LD[50] every three days for one month period. Hemoglobin value [HB], red blood cells [RBC], white blood cells [WBC] and platelets [PLT] counts, gamma glutamyl transferase [gammaGT] were determined in addition to histopathological examinations for liver, spleen and kidney. In general, both compounds induced significant changes in HB value, RBC, WBC, PLT counts, and gammaGT activity after 30 days from treatment. Ivermectin caused significant rise in creatinine level at the same period. Histopathological examination showed disturbance in hepatic lobules, inflammatory infiltration, and pyknotic and karyolitic nuclei in hepatocytes. Kidney exhibited lobulated glomeruli and degenerative tubules, but interstitial hemorrhagic areas were noticed in spleen. Although the tested compounds are biopesticides, obtained data revealed that both compounds caused undesirable effects on experimental animals, so we conclude not to use them on plants during fruit stage or on fresh vegetables

Ivermectina: sus múltiple usos, seguridad y toxicidad / Ivermectin: its multiple uses, safety and toxicity

La Ivermectina, con más de 30 años de uso en humanos, es una droga que aún sigue siendo estudiada en otras indicaciones. Su seguridad es alta; se han dado casi 2.000 millones de dosis en humanos con efectos colaterales mínimos. Se excreta por las heces, no es nefrotóxica ni hepatotóxica. Es el tratamiento de elección en pacientes con SIDA, recibiendo terapia HAART para estrongiloidiasis sistémica y sarna noruega. Es empleada en niños mayores de dos años de edad o con más de 15 kilos de peso. La dosis es de 200 microgramos/kg en forma oral, al 0,6 por ciento en gotas (1 gota/kg de peso) y de 400 microgramos/kg en forma tópica al 0,1 por ciento (0,4 cc/kg de peso). Logró erradicar la oncocercosis que produce la “ceguera del río” y fue considerada como el triunfo de la humanidad sobre la adversidad por la OMS en 2009.

Ivermectin has been used during more than 30 years and yet it is an old drug in search for additional indications. Ivermectin has high safety profile, and more than 2 billion doses have been administered with mild side effects. Ivermectin is metabolized in the liver, and the drug or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1percent of the oral dose excreted in the urine. The plasma half-life of ivermectin in humans is approximately 18 hours following oral administration. Ivermectin is primarily metabolized by CYP3A4, and does not provoke hepato /nephrotoxicicty. This molecule is the gold standard treatment for strongyloidiasis and crusted scabies in patients with AIDS during treatment with HAART therapy. Ivermectin is used in children older than 2 years or more than 15 kg weight. Oral ivermectin 0.6 percent dose is 200 micrograms/kg (1 drop per kg) and topical ivermectin 0.1 percent dose is 400 micrograms/kg (0.4 cc per kg). Ivermectin was able to eliminate human river blindness (onchocerciasis) and “represent one of the most triumphant public health campaigns ever waged in the developing world” by WHO in 2009.

Toxic effects of five insecticides and their mixture on male albino rats

Five insecticides namely; abamectin, carbosulfan, fenpropathrin, methomyl and profenofos were given by gavages to male albino rats. These insecticides were administered daily for 28 days with doses equaled 1/20 LD 50 either singly or in a mixture of all the insecticides together. The study revealed significant decreases in body and kidneys weights, while increases in liver weights in all the treatments. Most of the treatments induced significant elevations in serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST], while caused decreases in acetylcholinesterase [AChE] activities. Fenpropathrin and the mixture induced significant increase in total protein content of the serum, while the other treatments induced significant decreases. Creatinine concentrations recorded significant elevations in fenpropathrin and methomyl treatments, while significant decrease in case of Profenofos. Degenerative changes and granularity of hepatocytes with Kupffer cells activation were observed in the treatments with the mixture or and methomyl. Shrinking in Bowman's capsule and degenerative changes of epithelium lining renal tubules were observed in rats treated with the mixture. Moreover, necrotic changes associated with desquamation of epithelium lining tubules were shown in rats treated with the mixture, fenpropathrin and methomyl. From the biochemical data, the joint action was estimated for the mixture composed of the five insecticides. The mixture interacts antagonistically with most of the measured biochemical parameters

Evaluation of abamectin toxicity on some biochemical constituents and osmoregulation in freshwater fish Oreochromis niloticus [Tilapia niloticus]

Indiscriment use of pesticides have been elevated the risk of contamination in environment and aquatic organisms. Considering to the previous fact, the present study was done to investigate the alterations of some blood constituents and ionic regulation; as well as the histopathological alterations in tissues of gills and kidneys of freshwater fish, Oreochromis niloticus, following prolonged exposure to sub-lethal concentrations of abamectin insecticide at 14 days. The obtained results showed that abamectin treatment caused hypotriglyceridemia and hyperglycemia in fish exposed to the high concentration [103.68 micro gL[-1]]. In addition, hypercholesterolemia was detected in abamectin-exposed fish [by 50.48 and 103. 68 micro gL[-]] after 14 days of exposure. Also, a marked increase in the creatinine level was observed in abamectin-exposed fish by 103.68 micro gL-1 on day 14, with a significant decline in the level of sodium ions [Na[+]] and a significant elevation in the level of chloride ions [Cl[-]] in fish exposed to low concentration [50.48 micro gL[-1]] of abamectin. In contrast, a significant decrease in the level of chloride ions [Cl[-]] was detected in the high concentration of abamectin. Marked decrease in the level of plasma bound calcium [B.Ca] with hypoproteinemia and hypophosphatemia were recorded in fish exposed to low concentration [50.48 micro gL[-1]] of abamectin. On the contrary, a marked enhancement in the triiodothyronine level [T3] was noticed in fish following exposure to 50.48 micro gL[-1] of abamectin. The histopathological studies on the gills and kidneys revealed necrosis of lamella and infiltration of acidophils leukocyte in gills with degenerative changes in kidney tubules were observed at both concentrations of abamectin

Avaliação histomorfométrica do parênquima testicular de ratos adultos tratados com diferentes doses de ivermectina / Histomorphometric evaluation of testicular parenchyma of adult rats treated with different dosages of ivermectin

Avaliou-se o efeito da ivermectina sobre o parênquima testicular através da produção espermática diária e da eficiência da espermatogênese em ratos Wistar adultos tratados com diferentes dosagens (200, 400 e 600æg/kg). Pela avaliação histomorfométrica, o parênquima testicular e o processo espermatogênico dos ratos Wistar não sofreram qualquer efeito deletério da aplicação de ivermectina, o que foi confirmado pela manutenção da produção espermática diária por testículo, pelo rendimento intrínseco da espermatogênese (PED/g/t) e pela manutenção da estrutura do parênquima testicular. Com base nos resultados quantitativos e qualitativos da espermatogênese, é possível concluir que a ivermectina não tem efeito tóxico-degenerativo sobre o parênquima testicular de ratos Wistar adultos.

The aim of this work was to evaluate the ivermectin effect on the testicular parenchyma through the daily spermatic production and the efficiency of the spermatogenesis in adult Wistar rats treated with different dosages (200, 400 and 600æg/kg) of ivermectin. Based on the histomorfometric evaluation, ivermectin had no deleterious effect on the testicular parenchyma and spermatogesis, which one was confirmed through the maintenance of the daily spermatic input and intrinsic income of spermatogenesis (PED/g/t), as well as by the maintenance of the testicular parenchyma structure. Based on the quantitative and qualitative results of spermatogenesis, it is possible to conclude that ivermectin does not have toxic-degenerative effect on the testicular parenchyma of adult Wistar rats.

Aspectos clínicos e patogenéticos da intoxicação por abamectina em bezerros / Clinical and pathogenetic aspects of abamectin poisoning in calves

Estudaram-se os aspectos clínico-patológicos e patogenéticos verificados após a administração experimental subcutânea de diferentes doses de abamectina em nove bezerros. Também são apresentados os dados clínico-patológicos sobre a ocorrência de intoxicação iatrogênica por essa droga que resultaram em 74 mortes em bovinos nos Estados do Rio Grande do Sul, Pará, Maranhão, Paraíba e Mato Grosso do Sul. No presente estudo, dos nove bezerros submetidos à administração experimental, cinco morreram (quatro que receberam doses únicas de 6-10 vezes superior à recomendada e um que recebeu diariamente a dose terapêutica durante 11 dias). A intoxicação por abamectina induz a disfunções neurológicas, caracterizadas por uma fase inicial de hiperexcitabilidade, seguida por hipotonia muscular generalizada e depressão progressiva. Nenhuma alteração macroscópica ou microscópica foi observada no sistema nervoso central ou em qualquer outro órgão. Conclui-se que a abamectina é um medicamento que deve ser utilizado com restrições, pois há riscos de morte quando utilizado em bezerros jovens, até mesmo na dose terapêutica.

Clinic-pathological aspects and the pathogenesis of experimental abamectin poisoning were studied, after subcutaneous administration of different abamectin doses in 9 calves, as well as the clini-cal and pathological aspects of 74 cases of the iatrogenic poisoning with this drug in cattle, which occurred in the states of Rio Grande do Sul, Pará, Maranhão, Paraíba and Mato Grosso do Sul. From the 9 calves submitted to experimental administration of single doses, 5 calves died (4 calves received doses 6-10 times higher than recommended, and one received the therapeutic daily dose during 11 days). Abamectin poisoning induces neurological dysfunctions, characterized by an initial phase of hyperexcitability, followed by widespread muscular hypotony and progressive depression. No macroscopic or microscopic alterations were observed in the central nervous system or in any other organ. It is concluded that abamectin is an antihelmintic which should be used with restriction, because of the risks leading to death when used in young calves, even in therapeutic doses.

Resistência de Cooperia spp. e Haemonchus spp. às avermectinas em bovinos de corte / Resistance of Cooperia spp. and Haemonchus spp. to avermectins in beef cattle

Foram realizados dois testes de redução de ovos de helmintos por grama de fezes em bovinos naturalmente infectados. No primeiro teste utilizaram-se quatro grupos tratados: ivermectina 1 por cento (IVM), produto endectocida experimental (PEE), ivermectina LA 1 por cento (IVMLA) e doramectina 1 por cento (DRM). A contagem de ovos por gramas de fezes (OPG) foi realizada durante 14 dias pós-tratamento. Foram observadas as seguintes taxas de eficácia: IVM, -1,3 por cento; PEE, 100 por cento; IVMLA, 18,9 por cento e DRM 50,6 por cento. Os gêneros de helmintos encontrados foram Cooperia e Haemonchus. No segundo teste foram avaliadas moxidectina 1 por cento e abamectina 1 por cento, e ambas apresentaram eficácia acima de 99 por cento.

Comparative assessment of the in vitro sensitivity of Brugia malayi infective larvae to albendazole, diethylcarbamazine and ivermectin alone and in combination.

The antifilaricidal drugs ivermectin (IVM), diethylcarbamazine (DEC), and albendazole (ALB), used alone or in combinations against infective third-stage larvae (L3) of nocturnally subperiodic (NSP) Brugia malayi (Narathiwat strain), were tested in vitro for sensitivity, for 7 days. IVM alone reduced larval motility at concentrations of 10(-7), 10(-6), and 10(-5) M on day 3. DEC alone also had this effect at concentrations of 10(-6). 10(-5), and 10(-4) M on day 2. ALB alone did not have this effect throughout the experiment, at various concentrations. However, it had greater effect when used in combination with either DEC or IVM. The result also indicated that DEC or IVM, when used in combination with ALB at concentrations of 10(-6) M/10(-6) M, and 10(-5) M/10(-5) M was effectively better than each drug used alone at those concentrations. When both drug combinations were compared, ALB/DEC seemed to be more effective than ALB/IVM at a concentration of 10(-6) M/10(-6) M on day 3. Although IVM and DEC can reduce larval motility when used alone or in combination with ALB, they cannot kill these larvae in an in vitro cultivation, even at a high concentration (10(-5) M).

Metodo alternativo para el control de vectores de la enfermedad de Chagas. efecto de la ivermectina / Alternative method for the control of Chagas disease vectors. Ivermectine efect.

Ninfas de Rhodnius prolixus fueron alimentadas sobre ratones inoculados con diferentes concentraciones de Ivermectina(1,000; 100; 10; 5 microgramos) y se comparó con grupo tetigo sin Ivermectina. La droga produjo una letalidad de 100 por ciento, 100 por ciento, 62.5 por ciento y 50 por ciento respectivamente. Se comenta su uso como método alternativo en el control de los vectores de la Enfermedad de Chasgas