Cryptotanshinone protects against adriamycin-induced mitochondrial dysfunction in cardiomyocytes.
PHARMACEUTICAL BIOLOGY(2016)
Abstract
Context: The serious side effect of Adriamycin (ADR) is cardiomyopathy. Cryptotanshinone (CRY) is widely and safely used as antioxidant with MTD more than 5mg/g in rats (p.o).Objective: The objective of this study is to study the protection effects of CRY against ADR-induced mitochondrial dysfunction in cardiomyocytes.Materials and methods: The chemical administration lasted for 20 days with an effective dose of CRY (p.o.) at 50 mg/kg in rats. Mitochondrial respiratory chain complex activities, ATP generation, mitochondrial membrane potential (MMP), superoxide anion free radical, oxidative stress-relative enzymes, and mitochondrial biogenesis-relative factors in normal control, ADR (i.p., 1.25mg/kg), and ADR (i.p., 1.25mg/kg)+CYP (p.o., 50mg/kg) groups were detected.Results: 50mg/kg CRY significantly promoted the energy production of ATP (16.992.38nmol/g Pro) (Pro: Protein) by increasing the complexes activities except II (p>0.05). After the treatment of CRY, the suppressed MMP was increased while superoxide anion free radical (0.57 +/- 0.07/mg Pro) was inhibited markedly. Mitochondrial biogenesis-relative factors PGC-1, NRF-1, and TFAM were also promoted. Remarkable augmentations of NO, inducible nitric oxide synthase (iNOS), and increased activity of GSH-PX (p<0.05) were also detected after the treatment of CRY, while no obvious changes on the activity of nitric oxide synthase (cNOS; p>0.05) were observed.Discussion and conclusion: These results suggest that CRY protects against ADR-induced mitochondrial dysfunction in cardiomyocytes. It could be an ideal potential drug of cardioprotection.
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Key words
ATP generation,cardiovascular protection,mitochondrial biogenesis,mitochondrial complex activity,mitochondrial membrane potential,mitochondrial respiratory chain,oxidative stress,superoxide anion free radical
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