Doxorubicin-induced central nervous system toxicity and protection by xanthone derivative of Garcinia mangostana.
Neuroscience
; 175: 292-9, 2011 Feb 23.
Article
en En
| MEDLINE
| ID: mdl-21074598
Doxorubicin (Dox) is a potent, broad-spectrum chemotherapeutic drug used around the world. Despite its effectiveness, it has a wide range of toxic side effects, many of which most likely result from its inherent pro-oxidant activity. It has been reported that Dox has toxic effects on normal tissues, including brain tissue. The present study tested the protective effect of a xanthone derivative of Garcinia Mangostana against Dox-induced neuronal toxicity. Xanthone can prevent Dox from causing mononuclear cells to increase the level of tumor necrosis factor-alpha (TNFα). We show that xanthone given to mice before Dox administration suppresses protein carbonyl, nitrotyrosine and 4-hydroxy-2'-nonenal (4HNE)-adducted proteins in brain tissue. The levels of the pro-apoptotic proteins p53 and Bax and the anti-apoptotic protein Bcl-xL were significantly increased in Dox-treated mice compared with the control group. Consistent with the increase of apoptotic markers, the levels of caspase-3 activity and TUNEL-positive cells were also increased in Dox-treated mice. Pretreatment with xanthone suppressed Dox-induced increases in all indicators of injury tested. Together, the results suggest that xanthone prevents Dox-induced central nervous system toxicity, at least in part, by suppression of Dox-mediated increases in circulating TNFα. Thus, xanthone is a good candidate for prevention of systemic effects resulting from reactive oxygen generating anticancer therapeutics.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Doxorrubicina
/
Fármacos Neuroprotectores
/
Garcinia mangostana
/
Xantonas
/
Neurotoxinas
/
Antineoplásicos Fitogénicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neuroscience
Año:
2011
Tipo del documento:
Article
País de afiliación:
Tailandia
Pais de publicación:
Estados Unidos