Fipronil (F) a pesticide considered of second generation cause various toxic effects in target and non-target organisms including humans in which provoke neurotoxicity, having the antagonism of gamma-amino butyric acid (GABA) as their main mechanism for toxic action. GABAergic system has been involved in processes related to the memory formation and consolidation. The present work studied the importance of GABA to the mechanisms involved in the very early development of fipronil-induced memory impairment in rats. Memory behavior was assessed using new object recognition task (ORT) and eight radial arm maze task (8-RAM) to study effects on cognitive and spatial memory. Locomotor behavior was assessed using open field task (OF). The dose of fipronil utilized was studied through a pilot experiment. The GABA antagonist picrotoxin (P) was used to enhance fipronil effects on GABAergic system. Fipronil or picrotoxin decrease memory studied in ORT and 8-RAM tasks. Additionally, F and P co-exposure enhanced effects on memory compared to controls, F, and P, suggesting strongly a GABAergic effect. Weight gain modulation and fipronil in blood were utilized as animal's intoxication indicators. In conclusion, here we report that second-generation pesticides, such as fipronil, can have toxic interactions with the CNS of mammals and lead to memory impairment by modulating the GABAergic system.

Background:Pesticides have been extensively used around the word but concerns over their influence on environment and health is growing. Synthetic pyrethroids are potent insecticides considered to be neurotoxicant. Hypothesis: We hypothesize that perinatal exposure to type I (Cypermethrin ) and type II (d-Allehtrin) pyrethroids would produce behavioral effects on offspring during development. Methods: Pregnant Wistar rats were exposed during gestation and lactation periods, and their pups were evaluated for somatic and sensory motor changes after weaning, and for locomotor activity, motor coordination, and anxiety-like behavior at post natal day 23 and 75 (PND23 and PND25). Results: Cyp and All provoked somatic and sensory-motor reflex alterations in weaned pups. In PND23 pups both Cyp and All decreased locomotor activity and motor coordination, and provoke anxiogenic-like effect. In PND75 pups both Cyp and All decreased locomotor activity and motor coordination. Cyp but not All provoked anxiogenic-like effect. Conclusion: Perinatal exposure to selected type I (d-allethrin) and type II (cypermethrin) pyrethroids provoked physical and sensorymotor alterations in weaned pups and persistent behavioral effects during offspring development, suggesting Cyp with a major power to cause neurotoxicity through time.

Recent reports show that fipronil affects non-target organisms, including environmental species populations and potentially humans. We aimed to examine if fipronil exposure affects the systolic blood pressure and related biomarkers. Thus, fipronil was orally administered to rats (30 mg/kg/day) during 15 days (Fipronil group) or physiological solution (Control group). While fipronil increased significantly the systolic blood pressure (158±13 mmHg), no significant changes were observed in Control group (127±3 mmHg). Significantly, higher levels of fipronil in plasma were observed in Fipronil group (0.46±0.09 μg/mL versus 0.17±0.11 μg/mL in Control group). Fipronil group showed lower weight gain compared with Control group. While fipronil resulted in higher concentrations of endothelin-1, reduced antioxidant capacity and lower levels of circulating matrix metalloproteinase 2 (MMP-2) and nitric oxide (NO) metabolites compared to Control group, no alteration was observed in serum biomarkers of renal and hepatic/biliary functional abilities. Therefore, this study suggests that fipronil causes hypertension and endothelin-1 plays a key role. Also, these findings suggest that reductions of both MMP-2 and NO may contribute with the elevation of systolic blood pressure observed with fipronil.

RESUMO O fipronil é um inseticida de toxicidade seletiva amplamente empregado na agricultura e na medicina veterinária. Porém, há relatos de efeitos neurotóxicos dessa substância, que geram prejuízos para vertebrados. Avaliou-se a atividade locomotora, a coordenação motora e a atividade da enzima acetilcolinesterase cerebral em ratos expostos ao fipronil. Ratos Wistar machos adultos (n=15) receberam fipronil em dose de 30mg/kg, por via oral, durante 15 dias; o grupo controle (n=15) foi tratado com solução fisiológica, por via oral, no mesmo período. No 16° dia de experimentação, os animais foram submetidos aos testes de arena de campo aberto e hole board. No 17° dia, foram anestesiados e eutanasiados, procedendo-se à coleta de órgãos, e posteriormente foi feita a avaliação da AChE cerebral. A exposição ao fipronil não provocou alterações significativas sobre a coordenação motora e a atividade locomotora, porém gerou inibição significativa da atividade da acetilcolinesterase cerebral. Esses achados sugerem que o fipronil pode provocar efeitos neurotóxicos em curto prazo, os quais podem ser exacerbados caso a exposição seja prolongada.

The combined effects of environmental agents, as metals and pesticides, on human health, need be evaluated because human exposition occurs generally through mixtures, while regulatory assessment of neurotoxicity by these compounds is currently performed only on selected single substances. In the present study the effects of maternal exposure to 10 mg cadmium/l (as cadmium acetate) in drinking water and dimethoate 4 mg/kg (via gavage) during gestation on the development of motor activity (locomotion and motor coordination) and social behavior (anxiety-like behavior and aggressivity) were studied. The importance of the cholinergic system in the modulation of behaviors was studied using acetylcholinesterase (AChE) activity as a biomarker of effect. Cadmium (Cd) and dimethoate (DM) single exposition modified fetal programing for motor activity and social behavior at childhood and adulthood and leads to disturbs of the AChE activity. Exposition to the mixture of Cd and DM enhanced effects on fetal programing and AChE activity. The present results provide, for the first time, direct experimental evidence supporting that joint exposure to cadmium and dimethoate in uterus of rats seems additive and it is perturbs offspring development leading to harmful consequences on motor activity and social behavior, probably related to modulation of the cholinergic system. Our data suggest that added precautions regarding gestational exposure to metals and pesticide mixtures would be prudent to avoid the possibility of fetal programming.