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Basic Clin Pharmacol Toxicol ; 111(2): 137-41, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22429688

ABSTRACT

Breast cancer (BCa) was induced in vivo in female rats with 7,12-dimethylbenz(a)anthracene (DMBA). Two main questions were addressed. Firstly, would the carcinogenesis be accompanied by oxidative stress as signalled by superoxide dismutase, glutathione peroxidase, malondialdehyde and total nitrate? Secondly, would treating the rats additionally with a blocker of voltage-gated sodium channel (VGSC) activity, shown previously to promote BCa progression, affect the oxidative responses? The DMBA-induced increases in the antioxidant systems were completely blocked by the VGSC inhibitor RS100642, which also significantly prolonged the lifespan. We conclude that VGSC inhibition in vivo can significantly protect against oxidative stress and improve survival from tumour burden.


Subject(s)
9,10-Dimethyl-1,2-benzanthracene/toxicity , Mexiletine/analogs & derivatives , Oxidative Stress/drug effects , Sodium Channel Blockers/pharmacology , Animals , Disease Models, Animal , Female , Glutathione Peroxidase/genetics , Glutathione Peroxidase/metabolism , Malondialdehyde/metabolism , Mammary Neoplasms, Experimental/chemically induced , Mammary Neoplasms, Experimental/drug therapy , Mexiletine/pharmacology , Rats , Rats, Sprague-Dawley , Signal Transduction , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism
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