Evaluation Of The Effect Of Activated Carbon On Acute Toxicity Of Abamectin

Avermectin is a new type of macrolide antibiotic and dual-purposed biological insecticide miticide, widely used in agriculture and livestock. Avermectin is chemically stable and basically has no transformation and metabolism in animals. Toxicology studies show that avermectin has neurotoxicity and immunotoxicity. When used in large doses, avermectin can cross the blood-brain barrier of mammals into the central nervous system, preventing neurotransmitter transmission and causing human or animal poisoning, coma and even death. Recently, with the increasing use of bio-pesticides, the cases of avermectin acute poisoning caused by misuse and self-suicide are also increasing. But now there is no effective antidote for avermectin. So the elimination of poisons and relieve symptoms is key to successful treatment.Activated carbon, also known as activated carbon black, is the amorphous carbon black powder or granular. Because of its large specific surface area and excellent adsorption capacity, activated carbon can easily bind the foreign chemicals entered through intestinal tract and prevent toxics from producing toxic effects. So as a kind of gastrointestinal poison removal measures, activated carbon has significant application values. Plenty of in vitro, animal and healthy volunteer studies related to activated carbon adsorption efficiency proved it good effect.Object:In this study, we put avermectin as the start point to determine the efficacy of activated charcoal (AC) to prevent absorption of avermectin (AVM) in the event of overdose by in vitro experiments and animal test which can assess the effect of activated carbon for AVM without the interference of confounding factors.Method:1. In vitro study:Three concentrations of avermectin solutions(10,5and2.5g/L) with different pH value(pH1.9and pH7.0, respectively)were mixed with activated charcoal and control, respectively. The concentrations of avermectin were measured by UV-visible spectrophotometry after vibrated, incubated and centrifuged on different time points. Calculate the residue rate of avermectin and adsorption rate of activated carbon for avermectin.2. Animal Studies:The intact male rabbits were divided randomly into5treatment groups (A, B, C, D, and E). Treatment A was5mg/kg avermectin exposure, treatment B and C were5mg/kg avermectin with oral activated carbon(lg/kg)20min and2h after exposure respectively, treatment D was10mg/kg avermectin exposure, treatment E was lOmg/kg avermectin with oral activated carbon20min after exposure and treatment F was solvent control group.The subjects underwent a series of clinical and laboratory tests, including AVM blood and target organ concentrations, pharmacokinetics indicators, poisoning signs, mortality, etc.Results:1. In vitro study:(1) The avermectin was significantly decreased in activated charcoal group compared with control group and the absorption ability of activated charcoal was higher on low concentration of avermectin.(2) The stability of the activated carbon-avermectin complex is strong and basically dissociation does not occur in the gastrointestinal emptying time.2. Animal Studies:(1)5mg/kg group:There were obvious differences of the blood AVM concentration trends in rabbits and main pharmacokinetic parameters between group A and B, C (P<0.05). The area under concentration-time curve (AUC) was significantly decreased (P<0.05) when given AC. Concurrently, plasma clearances (CL) nearly doubled (P<0.05). In terms of peak concentrations (Cmax), the values of group B and C were lowered markedly compared to group A (P<0.05).(2)10mg/kg group:Depression signs of central nervous system of rabbits in group D were severe, and the gait score, fasciculation score, convulsions first time, convulsions grade time of death and mortality in group D were all higher than those of group E.Conclusion:1. The adsorption effect of activated carbon for avermectin is very well in vitro and related to the carbon/drug ratio.2. Oral carbon can significantly reduce the absorption of avermectin and accelerate the metabolism of avermectin in rabbit body, to lighten the rabbit poisoning symptoms, reduce mortality.