Oxidative stress in the in vivo DMBA rat model of breast cancer: suppression by a voltage-gated sodium channel inhibitor (RS100642).

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.

• Authors: Kadir Batcioglu, A Burcin Uyumlu, Basri Satilmis, Battal Yildirim, Neslihan Yucel, Hakan Demirtas, Rustem Onkal, R Mine Guzel, Mustafa B A Djamgoz
• Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 111 Issue 2 Pg. 137-41 (Aug 2012) ISSN: 1742-7843 [Electronic] England
• PMID: 22429688 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.

Chemical References

• RS100642
• Sodium Channel Blockers
• Mexiletine
• Malondialdehyde
• 9,10-Dimethyl-1,2-benzanthracene
• Glutathione Peroxidase
• Superoxide Dismutase

Topics

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