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Title: A combination of an iron chelator with an antioxidant exerts greater efficacy on cardioprotection than monotherapy in iron-overload thalassemic mice
Authors: Sirinart Kumfu
Juthamas Khamseekaew
Siripong Palee
Somdet Srichairatanakool
Suthat Fucharoen
Siriporn C. Chattipakorn
Nipon Chattipakorn
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 2-Jan-2018
Abstract: © 2017 Informa UK Limited, trading as Taylor & Francis Group. Many recent studies have shown that antioxidant compounds decrease cardiac oxidative stress, decrease cardiac iron deposition, and improve cardiac dysfunction in iron-overload induced cardiomyopathy in animal models. Interestingly, a therapy including the combination of the iron chelator deferiprone (DFP) plus the antioxidant N-acetylcysteine (NAC) has been shown to significantly decrease oxidative stress and restore heart and brain function in iron-overloaded rats. However, the cardioprotective effects of this combined DFP and NAC treatment in thalassemic mice have not been investigated. We hypothesised that the combination of DFP and NAC exerts better cardioprotection than monotherapy via decreasing cardiac iron accumulation, oxidative stress, and apoptosis in thalassemic mice. The iron-overload condition was induced in heterozygous βKOHT and wild-type mice by instigating high iron diet consumption (FE) for three months. Then, iron chelator DFP (75 mg/kg/day twice a day), antioxidant NAC (100 mg/kg/day once a day), and combined DFP plus NAC were fed via oral gavage for one month with continuous iron feeding. Left ventricular (LV) function, heart rate variability (HRV), apoptosis, and cardiac iron accumulation were determined. Chronic iron-overload in mice led to increased cardiac iron deposition, oxidative stress, apoptosis, and impaired LV function and HRV. Although DFP and NAC showed similar cardioprotective efficacy, combined DFP plus NAC exerted greater efficacy in reducing both cardiac iron deposition and cellular apoptosis than monotherapy. In conclusion, combined iron chelator and NAC treatment exert the greatest cardioprotective efficacy when compared with either of the monotherapies in iron-overload thalassemic mice.
ISSN: 10292470
Appears in Collections:CMUL: Journal Articles

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