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INTRODUCTION:Alcohol (EtOH) use disorders (AUDs) represent a substantial public health problem worldwide. Over 76million people present with AUDs 2.5 million deaths were attributed to alcohol (World Health Organization,2010). Channadshelshi has been used for treatment of alcohol-related, liver disease and intoxication intraditional medicine.GOAL:To determine effect of channadshelshi on voluntary alcoholic wistar rats.MATERIALS AND METHODS:To examine acute toxicity of Channadselshi were used V.P.Prozorovsky express method (1978) andOECD (2001).Voluntary EtoH consumption measurement (two-bottle choice, intermittent access to EtOH paradigm inwistar rats). Water and 20% ethanol were presented in 200 mlgraduated plastic cylinders with stainlesssteeldrinking spouts.The experiment period was 10 weeks total. EtOH consumption was expressed asgrams of EtOH consumed per kilogram of body weight/day.Elevated plus maze. Anxiety associated with EtoH withdrawalwas measured on EPM The mazewaselevated 1 m above the floor and contained four 50 cm long, 10 cmwidearms arranged at rightangles. The closed arms had opaque walls 30cm high, extending the length of the arm. At the time of thetest, eachanimal was placed in the center of the maze facing an open arm andallowed to explore for a5 min session. During this 5 min test session, theanimal’s number of arm entries and time spent in eacharm per entry was recorded on a camera.Pentylenetetrazol (PTZ) 100 mg/kg dose used in this study was determined as the dose that inducedseizures and protection against mortality in miceThe experimental protocol was approved by the Ethics Committee of the MNUMS. (№ 14-11/1À)RESULTS:LD50 of Channadselshi extract was found to be LD50=2.58 (2.1-3.2) gr/kg by V.P.Prozorovsky expressmethod (1978). Channadselshi was no acute toxic by OECD (2001).Ten and four weeks oral administration of Channadselshi (200 mg/kg) significantly (P<0.01) decreasedthe consumption of ethanol and significantly (P<0.01) increased time spent in open arm (EPM) involuntary alcoholic wistar rat compare to control.The time (sec) of latency the generalized convulsion were significantly (P<0.01) increased ofChannadselshi compare to control. The percent of protection against mortality were 80% in PTZinduced seizure in mice.CONCLUSIONS:1. Our study showed that Channadselshi hasreduced consumption of ethanol in voluntary alcoholicwistar rat.2. Channadselshi has central nervous system protection effect against PTZ induced seizure in mice.
RESUMEN
Chlorpyrifos (CPF) is an organophosphate compound used worldwide as a pesticide in agriculture that, after subcutaneous injection, keeps acetylcholinesterase (AChE) activity inhibited within an organism for months. Ample clinical and experimental evidence shows that CPF exposure induces relevant and persistent neurobehavioral deficits in humans and animals, even after one single episode/injection. Additionally, clinical and epidemiological studies evidence that a significant percentage (60%) of Gulf War veterans as well as agricultural workers suffering from acute OP intoxication may have developed intolerance to nicotine and ethanol-containing beverages. Consistent with it, administration of a single high dose of CPF to adult Wistar rats elicited long-lasting reduced voluntary ethanol drinking and increased sedation to ethanol without evidence of altered ethanol metabolism, which indicates that CPF-ethanol neurobiological interactions may exist. In this study, we explore whether CPF exposure induces significant disturbances in basal and/or ethanol-evoked neural activity in a set of cholinoceptive brain regions critically involved with neurobiological responses to ethanol. For this aim, brain regional c-fos expression in response to acute ethanol (1.5 or 3.0 g/kg, i.p.) or saline was assessed in adult male Wistar rats previously injected with either a single high dose of CPF (250 mg/kg, sc) or vehicle. We found that CPF administration reduces long-term basal, but not ethanol-evoked, c-fos expression in the arcuate hypothalamic nucleus. Because independent brain pathways may modulate acute responses to ethanol and voluntary ethanol consumption, we do not rule out the contribution of basal neural disturbances observed in the Arc to CPF-elicited ethanol avoidance.
El clorpirifós (CPF) es un compuesto organofosforado utilizado como plaguicida en todo el mundo. Después de ser inyectado de manera subcutánea, mantiene la actividad de la enzima acetilcolinesterasa (AChE) inhibida durante meses. Estudios clínicos y experimentales muestran que la exposición al CPF induce déficits neuroconductuales persistentes en seres humanos y animales, incluso después de un solo episodio/inyección. Además, estudios epidemiológicos evidencian que un porcentaje significativo (60%) de los veteranos de la Guerra del Golfo, así como los agricultores que sufren una intoxicación aguda por organofosforados, desarrollan intolerancia a la nicotina y las bebidas que contienen etanol. Datos experimentales mostraron que la administración de una sola dosis alta de CPF en ratas Wistar adultas provoca una reducción a largo plazo del consumo voluntario de etanol y un incremento en la sedación provocada por etanol sin evidencias de alteración del metabolismo de esta sustancia, lo que indica que pueden existir interacciones neurobiológicas entre CPF-etanol. En este estudio, se explora si la exposición a CPF induce alteraciones significativas en la actividad neuronal basal o evocada por el etanol en un conjunto de regiones colinoceptivas del cerebro involucradas en las respuestas neurobiológicas al etanol. Para ello, se evaluó la expresión de c-fos en respuesta a una dosis de etanol aguda (1.5 o 3.0 g/kg, ip) o solución salina en ratas Wistar macho adultas previamente inyectados con dosis aguda de CPF (250 mg/kg, sc) o un vehículo. Encontramos que la administración de CPF redujo la expresión basal de c-fos a largo plazo, pero no la evocada por el etanol en el núcleo arqueado del hipotalámo. Debido a que vías cerebrales independientes podrían modular las respuestas agudas al etanol y el consumo voluntario del mismo, no se descarta la contribución de las alteraciones neuronales basales observadas en el Arc en la evitación del consumo de etanol provocado por CPF.