Mangiferin at 60 mg/kg/day significantly decreased TNF-α by 44.55%, caspase-9 by 52.79%, and cytosolic calcium levels by 24.15% in doxorubicin-induced rats (p<0.05).
Does mangiferin prevent doxorubicin-induced cardiotoxicity in rats?
Mangiferin at 60 mg/kg/day demonstrates cardioprotective effects against doxorubicin-induced cardiotoxicity in rats by modulating intracellular calcium homeostasis and reducing inflammation and apoptosis.
valor p: p=< 0.05
Context: The molecular mechanism of doxorubicin (DOX) cardiotoxicity involves overproduction of free radicals that leads to intracellular calcium dysregulation and apoptosis. Mangiferin (MGR), a naturally occurring glucosylxanthone, has antioxidant and cardioprotective properties. However, its cardioprotection mechanism has yet to be revealed.Objective: This study determines whether the cardioprotective effect of MGR is caused by its effect on intracellular calcium regulation.Materials and methods: Male Sprague–Dawley rats were induced by DOX intraperitoneally with a total dose of 15 mg/kg bw. MGR was given orally at the doses of 30 and 60 mg/kg bw/d for seven consecutive weeks. The parameters examined were mRNA expression levels of proinflammatory cytokine gene (TNF-α), calcium regulatory gene (SERCA2a) and proapoptotic genes (caspase-9 and caspase-12), as well as cytosolic and mitochondrial calcium levels.Results: Treatment with MGR at 60 mg/kg bw/d significantly decreased the mRNA expression levels of TNF-α by 44.55% and caspase-9 by 52.79%, as well as the cytosolic calcium level by 24.15% (p 0.05). Meanwhile, MGR 30 mg/kg bw/d gave insignificant results in all parameters.Discussion and conclusion: MGR protected against DOX-induced cardiac inflammation and apoptosis via down-regulation of proapoptotic and proinflammatory gene expressions, upregulation of SERCA2a gene expression, and normalization of cytosolic calcium level. Thus, the cardioprotective effect of MGR is at least in part due to the regulation of intracellular calcium homeostasis.
Agustini et al. (Tue,) conducted a other in Doxorubicin-induced cardiotoxicity. Mangiferin was evaluated on mRNA expression levels of TNF-α, SERCA2a, caspase-9, caspase-12, and cytosolic and mitochondrial calcium levels (p=< 0.05). Mangiferin at 60 mg/kg/day significantly decreased TNF-α by 44.55%, caspase-9 by 52.79%, and cytosolic calcium levels by 24.15% in doxorubicin-induced rats (p<0.05).
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