Experimental study on the toxicokinetics and gastrointestinal damage in rats poisoned with acute diquat poisoning at different exposure doses / 中华危重病急救医学

OBJECTIVE@#To observe the toxicokinetic parameters, absorption characteristics and pathomorphological damage in different parts of the gastrointestinal tract of rats poisoned with different doses of diquat (DQ).@*METHODS@#Ninety-six healthy male Wistar rats were randomly divided into a control group (six rats) and low (115.5 mg/kg), medium (231.0 mg/kg) and high (346.5 mg/kg) dose DQ poisoning groups (thirty rats in each dose group), and then the poisoning groups were randomly divided into 5 subgroups according to the time after exposure (15 minutes and 1, 3, 12, 36 hours; six rats in each subgroup). All rats in the exposure groups were given a single dose of DQ by gavage. Rats in the control group was given the same amount of saline by gavage. The general condition of the rats was recorded. Blood was collected from the inner canthus of the eye at 3 time points in each subgroup, and rats were sacrificed after the third blood collection to obtain gastrointestinal specimens. DQ concentrations in plasma and tissues were determined by ultra-high performance liquid chromatography and mass spectrometry (UPHLC-MS), and the toxic concentration-time curves were plotted to calculate the toxicokinetic parameters; the morphological structure of the intestine was observed under light microscopy, and the villi height and crypt depth were determined and the ratio (V/C) was calculated.@*RESULTS@#DQ was detected in the plasma of the rats in the low, medium and high dose groups 5 minutes after exposure. The time to maximum plasma concentration (Tmax) was (0.85±0.22), (0.75±0.25) and (0.25±0.00) hours, respectively. The trend of plasma DQ concentration over time was similar in the three dose groups, but the plasma DQ concentration increased again at 36 hours in the high dose group. In terms of DQ concentration in gastrointestinal tissues, the highest concentrations of DQ were found in the stomach and small intestine from 15 minutes to 1 hour and in the colon at 3 hours. By 36 hours after poisoning, the concentrations of DQ in all parts of the stomach and intestine in the low and medium dose groups had decreased to lower levels. Gastrointestinal tissue (except jejunum) DQ concentrations in the high dose group tended to increase from 12 hours. Higher doses of DQ were still detectable [gastric, duodenal, ileal and colonic DQ concentrations of 6 400.0 (1 232.5), 4 889.0 (6 070.5), 10 300.0 (3 565.0) and 1 835.0 (202.5) mg/kg respectively]. Light microscopic observation of morphological and histopathological changes in the intestine shows that acute damage to the stomach, duodenum and jejunum of rats was observed 15 minutes after each dose of DQ, pathological lesions were observed in the ileum and colon 1 hour after exposure, the most severe gastrointestinal injury occurred at 12 hours, significant reduction in villi height, significant increase in crypt depth and lowest V/C ratio in all segments of the small intestine, damage begins to diminish by 36-hour post-intoxication. At the same time, morphological and histopathological damage to the intestine of rats at all time points increased significantly with increasing doses of the toxin.@*CONCLUSIONS@#The absorption of DQ in the digestive tract is rapid, and all segments of the gastrointestinal tract may absorb DQ. The toxicokinetics of DQ-tainted rats at different times and doses have different characteristics. In terms of timing, gastrointestinal damage was seen at 15 minutes after DQ, and began to diminish at 36 hours. In terms of dose, Tmax was advanced with the increase of dose and the peak time was shorter. The damage to the digestive system of DQ is closely related to the dose and retention time of the poison exposure.

Mortalidade de abelhas sem ferrão Scaptotrigona bipunctata sob os efeitos dos herbicidas paraquat e diquat / Mortality of Scaptotrigona bipunctata stingless bees under the effects of paraquat and diquat herbicides / Mortalidad de abejas sin aguijón Scaptotrigona bipunctata bajo los efectos de los herbicidas paraquat y diquat

As abelhas exercem essencial atividade polinizadora, além de fundamentais na manutenção ecossistêmica, também polinizam diversos sistemas agrícolas. São crescentes os relatos sobre o desaparecimento de abelhas, possivelmente em decorrência do intenso uso de agrotóxicos, os quais não possuem seus efeitos sobre a biodiversidade, de fato, conhecidos. A maioria dos estudos nessa área é voltada para a compreensão dos efeitos de inseticidas, porém, os herbicidas também podem influenciar na mortandade dos insetos polinizadores. Referente aos herbicidas paraquat e diquat, amplamente utilizados na agricultura, pouco se conhece sobre os efeitos que atingem organismos não-alvo, como as abelhas. Este trabalho avaliou a mortalidade das abelhas Scaptotrigona bipunctata submetidas aos herbicidas paraquat e diquat, via contato e ingestão. Dois experimentos foram conduzidos no delineamento de blocos casualizados em esquema fatorial 2 x 2 com tratamento adicional, em três repetições. Os tratamentos foram: dois herbicidas (paraquat e diquat), duas doses (50 e 100%) e um tratamento adicional sem exposição ao produto (controle). Cada parcela consistiu em dez indivíduos, expostos aos tratamentos e incubados à 28oC durante 72 horas em ambiente controlado. Para o experimento de ingestão, ambas as doses dos herbicidas resultaram em maior mortalidade de abelhas em relação à condição controle. Ademais, a dose 100% resultou em maior toxicidade comparada à dose 50%. Para a contaminação via contato, não houve aumento na mortalidade das abelhas perante a exposição. Conclui-se que a contaminação por ingestão com os herbicidas paraquat e diquat pode afetar a sobrevivência das abelhas sem ferrão, podendo em longo prazo alterar a viabilidade e a dinâmica das populações das abelhas Scaptotrigona bipunctata.(AU)

Bees have essential pollinating activities and are fundamental to the maintenance of the ecosystem since they also pollinate various agricultural systems. There are growing reports about the disappearance of bees, possibly due to the intense use of pesticides, which do not have their effects on biodiversity fully known. Most studies in this area are aimed at understanding the effects of insecticides; however, herbicides can also influence the mortality of pollinating insects. Regarding the paraquat and diquat herbicides, widely used in agriculture, little is known about the effects on non-target organisms, such as bees. This work evaluated the mortality of Scaptotrigona bipunctata bees submitted to the paraquat and diquat herbicides via contact and ingestion. Two experiments were conducted in a randomized block design in a 2 x 2 factorial scheme with additional treatment, in three replications. The treatments were: two herbicides (paraquat and diquat), two doses (50 and 100%), and an additional treatment without contamination (control). Each plot consisted of ten individuals exposed to treatments and incubated at 28 ºC for 72 hours in a controlled environment. For the ingestion experiment, both doses of the herbicides resulted in higher bee mortality when compared to the control condition. In addition, the 100% dose resulted in greater toxicity when compared to the 50% dose. For contact contamination, there was no increase in bee mortality on exposure. It can be concluded that contamination by ingestion of paraquat and diquat can affect the survival of stingless bees, which in the long term may alter the viability and population dynamics of Scaptotrigona bipunctata bees.(AU)

Las abejas ejercen una actividad polinizadora esencial, además de ser fundamentales en el mantenimiento de los ecosistemas, también polinizan varios sistemas agrícolas. Cada vez hay más informes sobre la desaparición de abejas, posiblemente como consecuencia del uso intenso de pesticidas, que no tienen sus efectos sobre la biodiversidad, de hecho, conocidos. La mayoría de los estudios en esta área tienen como objetivo comprender los efectos de los insecticidas, sin embargo, los herbicidas también pueden influir en la mortalidad de los insectos polinizadores. Con respecto a los herbicidas paraquat e diquat, ampliamente utilizados en la agricultura, se sabe poco sobre los efectos que afectan a organismos no objetivo, como las abejas. Esta investigación evaluó la mortalidad de abejas Scaptotrigona bipunctata sometidas a herbicidas paraquat y diquat, por contacto e ingestión. Dos experimentos fueron conducidos en el delineamiento de bloques casualizados en esquema factorial 2 x 2 con tratamiento adicional, en tres repeticiones. Los tratamientos fueron: dos herbicidas (paraquat y diquat) dos dosis (50 y 100%) y un tratamiento adicional sin exposición al producto (control). Cada parcela estuvo compuesta por diez individuos, expuestos a tratamientos e incubados a 28ºC durante 72 horas en ambiente controlado. Para el experimento de ingestión, ambas dosis de herbicidas resultaron en mayor mortalidad de abejas en comparación con la condición de control. Además, la dosis del 100% resultó en mayor toxicidad en comparación con la dosis del 50%. Para la contaminación por contacto, no hubo un aumento en la mortalidad de las abejas debido a la exposición. Se concluye que la contaminación por ingestión con herbicidas paraquat y diquat puede afectar la supervivencia de las abejas sin aguijón, lo que a largo plazo puede alterar la viabilidad y la dinámica poblacional de las abejas Scaptotrigona bipunctata.(AU)

Intoxicação por diquat / Diquat intoxication

O paraquat e o diquat são herbicidas de contacto do grupo dos bipiridilos, utilizados largamente para controlo de ervas daninhas. A importância deste grupo de herbicidas reside na sua utilização frequente para fins suicidas e pela inexistência de antídoto ou tratamento médico específico. O envenenamento com diquat é muito menos comum que com o paraquat e por isso existem poucos casos descritos na literatura. A dose letal de ambos é sobreponível, contudo o diquat é considerado menos tóxico devido ao menor dano pulmonar. Por outro lado, o diquat tem efeitos tóxicos graves sobre o sistema nervoso central. Por este motivo os sinais de neurotoxicidade pelo diquat são os mais relevantes e incluem sinais de parkinsonismo. O rim é a principal via excretora do diquat e a necrose tubular aguda é a lesão tipicamente identificada. A sobrevida depende de dois fatores: a concentração da substância no plasma e o tempo após a ingestão. O tratamento centra-se em três pontos essenciais: prevenção da absorção, rápida excreção e modificação dos efeitos tecidulares. A hemoperfusão é mais eficaz na clearance do diquat do que a hemodiálise e a sua utilização nas primeiras 12 horas de intoxicação pode reduzir a mortalidade.

Paraquat and diquat are contact herbicides from bipyridyl group, commonly used in weed control. The importance of this herbicide group is due to its frequent use with suicidal purpose and because there is neither an antidote nor a specific treatment. Poisoning with diquat is much less common that with paraquat, so there are few cases published in literature. The lethal dose of both is similar, however diquat is considered less toxic because it causes less lung damage. On the other side, diquat has severe toxic effects on central nervous system and neurotoxic signs are the more relevant, and include Parkinsonism. The kidney is the main excretory pathway of diquat and acute tubular necrosis is typical. Survival depends on two factors: plasma concentration and time of ingestion. Treatment focus in three key points: preventing absorption, rapid excretion and tissue effects. Hemoperfusion is more effective in diquat clearance than haemodialysis and its use in first 12 hours can reduce mortality.