Publication: Evaluación del efecto del agonista cannabinoide WIN 55,212-2 en el tratamiento de los efectos secundarios producidos por el fármaco antineoplásico 5-fluorouracilo en rata
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2016
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Abstract
Los efectos secundarios producidos por la quimioterapia anticancerosa suponen un problema para el que se han propuesto los cannabinoides como tratamiento (a pesar de su principal limitación, los efectos centrales). El antineoplásico 5-Fluorouracilo (5-FU) produce en los pacientes náuseas, vómitos, diarrea, neuropatía periférica y, posiblemente, dolor visceral. Se evaluó si el agonista cannabinoide WIN 55, 212-2 (WIN), a dosis no psicoactivas, puede ser efectivo para tratar dichos efectos secundarios. Métodos: Se administró WIN (1 mg/kg/día, intraperitoneal, 4 días) y/o 5-FU (150 mg/kg/día, intraperitoneal, 2 días) a 44 ratas Wistar, distribuidas en 4 grupos: vehículo+salino (n=10), WIN+salino (n=10), vehículo+5-FU (n=12) y WIN+5-FU (n=12). Se evaluó la motilidad gastrointestinal usando métodos radiográficos no invasivos (día 1 y 4), y la presencia de alodinia mecánica (test de von Frey) y los efectos psicoactivos del WIN (tétrada cannabinoide) (día 3). Resultados: El 5-FU produjo dismotilidad gástrica (pero no diarrea) y neuropatía periférica. El cannabinoide, sin efectos centrales, fue capaz de prevenir la neuropatía pero no la dismotilidad. Conclusión: Los cannabinoides, incluso a dosis no psicoactivas, podrían ser útiles para el tratamiento de algunos de los efectos secundarios de los antineoplásicos.
Cancer chemotherapy induce important side effects which cannabinoids might palliate or even prevent. In patients, the antineoplastic drug 5-Fluorouracil (5-FU) produces nausea, emesis, diarrhea, peripheral neuropathy and, probably, visceral pain. The cannabinoid agonist WIN 55,212-2 (WIN) was used at a non-psychoactive dose to see if it avoids these side effects in a rat model. Methods: WIN (1 mg/kg/day, intraperitoneal, 4 days) and/or 5-FU (150 mg/kg/day, intraperitoneal, 2 days) were administered to 44 Wistar rats, distributed in 4 groups: saline+vehicle (n=10), saline+WIN (n=10), 5-FU+vehicle (n=12) and WIN+5-FU (n=12). We evaluated gastrointestinal motility with radiographic non-invasive methods (day 1 and 4), and the presence of mechanical allodynia (Von Frey test) and psychoactive effects of WIN (cannabinoid tetrad) (day 3). Results: 5-FU produced gastric dysmotility (but not diarrhea) and peripheral neuropathy. The cannabinoid, without central effects, prevented neuropathy but not gastric dysmotility. Conclusion: Cannabinoids, even at a non-psychoactive dose, could be useful to treat some chemotherapy-induced side effects.
Cancer chemotherapy induce important side effects which cannabinoids might palliate or even prevent. In patients, the antineoplastic drug 5-Fluorouracil (5-FU) produces nausea, emesis, diarrhea, peripheral neuropathy and, probably, visceral pain. The cannabinoid agonist WIN 55,212-2 (WIN) was used at a non-psychoactive dose to see if it avoids these side effects in a rat model. Methods: WIN (1 mg/kg/day, intraperitoneal, 4 days) and/or 5-FU (150 mg/kg/day, intraperitoneal, 2 days) were administered to 44 Wistar rats, distributed in 4 groups: saline+vehicle (n=10), saline+WIN (n=10), 5-FU+vehicle (n=12) and WIN+5-FU (n=12). We evaluated gastrointestinal motility with radiographic non-invasive methods (day 1 and 4), and the presence of mechanical allodynia (Von Frey test) and psychoactive effects of WIN (cannabinoid tetrad) (day 3). Results: 5-FU produced gastric dysmotility (but not diarrhea) and peripheral neuropathy. The cannabinoid, without central effects, prevented neuropathy but not gastric dysmotility. Conclusion: Cannabinoids, even at a non-psychoactive dose, could be useful to treat some chemotherapy-induced side effects.
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Mención en Biología Sanitaria, Curso 2015/2016