Yanshan Zhang1, Liang Chen2, Fan Li3, Huijuan Wang4, Yunyi Yao5, Jiamei Shu6, Ming-Zhong Ying3. 1. a Department of Tumor Surgery , Wuwei Tumor Hospital , Wuwei, Gansu PR China . 2. b Department of Paediatrics , Changhai Hospital, Second Military Medical University , Shanghai , PR China . 3. c International Medical Center, Chinese PLA General Hospital , Beijing PR China . 4. d Department of Tumor Chemotherapy , Wuwei Tumor Hospital , Wuwei, Gansu , PR China . 5. e Research Center for Biochemistry and Molecular Biology, Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College , Xuzhou, Jiangsu , PR China , and. 6. f Department of Cardiology , The Second Affiliated Hospital of Soochow University , Suzhou, Jiangsu PR China.
Abstract
CONTEXT: The serious side effect of Adriamycin (ADR) is cardiomyopathy. Cryptotanshinone (CRY) is widely and safely used as antioxidant with MTD more than 5 mg/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., 1.25 mg/kg), and ADR (i.p., 1.25 mg/kg) + CYP (p.o., 50 mg/kg) groups were detected. RESULTS: 50 mg/kg CRY significantly promoted the energy production of ATP (16.99 ± 2.38 nmol/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-1α, 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.
CONTEXT: The serious side effect of Adriamycin (ADR) is cardiomyopathy. Cryptotanshinone (CRY) is widely and safely used as antioxidant with MTD more than 5 mg/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., 1.25 mg/kg), and ADR (i.p., 1.25 mg/kg) + CYP (p.o., 50 mg/kg) groups were detected. RESULTS: 50 mg/kg CRY significantly promoted the energy production of ATP (16.99 ± 2.38 nmol/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-1α, 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.