Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract

Bagchi, Debasis; Sen, Chandan K.; Ray, Sidhartha D.; Das, Dipak K.; Bagchi, Manashi; Preuss, Harry G.; Vinson, Joe A.

doi:10.1016/s0027-5107(02)00324-x

Cited by 359 publications

(267 citation statements)

References 35 publications

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“…Studies have shown that the apoptosis of cardiomyocytes, as characterized by caspase activation, caspase-mediated proteolytic degradation, and internucleosomal DNA cleavage, contributes to the development of myocardial dysfunction in heart failure (Maejima et al, 2005). Doxorubicin-induced apoptosis is mediated by a decreased the expression of Bcl-2 and an increased the expression of caspase-3 in cardiomyocytes (Wu et al, 2002;Bagchi et al, 2003;Takemura and Fujiwara, 2007). Bcl-2 is known as a critical inhibitor of apoptosis and prevents the release from mitochondria into the cytosol of apoptogenic factors, including cytochrome c and apoptosis-inducing factor.…”

Section: Discussionmentioning

confidence: 99%

“…Some research groups have reported that flavonoids exhibit protective effects against cardiomyopathy and cardiomyocyte apoptosis induced by doxorubicin (Bagchi et al, 2003;Hüsken et al, 1995). The Chinese traditional medicine Dracocephalum rupestre Hance, a wild perennial herb found throughout western China, is a rich resource of flavonoids (Wu and Li, 1977).…”

Section: Introductionmentioning

confidence: 99%

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Protective effects of naringenin-7-O-glucoside on doxorubicin-induced apoptosis in H9C2 cells

Han

Ren

Fan

et al. 2008

European Journal of Pharmacology

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Doxorubicin, a widely used chemotherapeutic agent, can give rise to severe cardiotoxicity by inducing cardiomyocyte apoptosis. Dracocephalum rupestre Hance, a Chinese traditional herb, has therapeutic potential for cardiovascular diseases. Naringenin-7-O-glucoside is the main active constituent of D. rupestre and there is increasing interest in its therapeutic applications. The aim of this study was to evaluate the effects of naringenin-7-O-glucoside on cardiomyocyte apoptosis induced by doxorubicin. Cell viability was detected by MTT assay. Naringenin-7-Oglucoside (10, 20, and 40 μM) significantly enhanced cardiomyocyte proliferation relative to that of doxorubicin. Furthermore, naringenin-7-Oglucoside increased the protein levels of heme oxygenase-1 (HO-1) and Bcl-2 in cardiomyocytes (as detected by Western blotting) and suppressed the mRNA expression of caspase-3 and caspase-9 (as detected by RT-PCR). These results suggest that naringenin-7-O-glucoside has protective effects against doxorubicin-induced apoptosis, effects which could underlie the use of naringenin-7-O-glucoside therapeutic agent for treating or preventing cardiomyopathy associated with doxorubicin.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protective effects of naringenin-7-O-glucoside on doxorubicin-induced apoptosis in H9C2 cells

Han

Ren

Fan

et al. 2008

European Journal of Pharmacology

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“…12 Grape seed proanthocyanidin extract (GSPE) has been shown to have antioxidant effects in various in vivo and in vitro studies. 12,13 For the first time in the literature, we aimed to investigate the effectiveness of GSPE in the prevention of AK-induced nephropathy by monitoring changes in blood urea nitrogen (BUN), creatinine, as well as renal histopathological changes. We also examined renal total oxidant system (TOS), total antioxidant system (TAS), oxidative stress index (OSI), and malondialdehyde (MDA) levels in order to understand whether the damage occurs via the oxidative system.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Grape Seed Proanthocyanidin Extract in Preventing Amikacin-Induced Nephropathy

et al. 2012

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Background/Aims: Nephrotoxicity induced by aminoglycosides (AGs) limits their clinical use. As yet, no molecules have been approved to prevent AG nephropathy. We aim to investigate the effectiveness of grape seed proanthocyanidin extract (GSPE) in the prevention of amikacin (AK)-induced nephrotoxicity. Methods: A total of 24 rats were allocated into control, GSPE, AK, and AK + GSPE groups. While 1 mL saline was administered for 6 days in control and AK groups, 100 mg/kg GSPE was administered in GSPE and AK + GSPE groups. On day 7, intraperitoneal (i.p.) saline was administered in control and GSPE groups, while 1.2 g/kg i.p. AK was administered in AK and AK + GSPE groups. The experiment was terminated on day 9. Blood samples were taken for the measurement of renal functions. Renal tissues of the rats were removed for the analysis of malondialdehyde (MDA), total oxidant system (TOS), total antioxidant system, oxidative stress index (OSI), and for histopathological examination. Results: MDA level was found to be lower in GSPE group compared with other study groups. There was significantly more renal histopathological damage and higher blood urea nitrogen, creatinine, TOS, OSI, and MDA levels in the AK group compared with the control and AK + GSPE groups. The same parameters showed significant improvement in AK + GSPE group compared with AK group. Conclusion: Our findings demonstrate for the first time that GSPE reduces oxidative damage in AK nephropathy and provides biochemical and renal histopathological improvements.

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“…New cytoprotective compounds are being investigated. Researchers concentrate on numerous antioxidative compounds, such as melatonin, coenzyme Q, amifostin, flavonoid compounds, essential fatty acids, L-carnitine, selenium (22,23,24). In our research we concentrated on carnosine, a dipeptide commonly occurring in human body, which also shows antioxidative properties.…”

Section: Discussionmentioning

confidence: 99%

Effects of Carnosine on the Toxicity of Doxorubicin in Rabbits and Mice

et al. 2003

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The aim of this study was to establish the effect of naturally occurring antioxidant -carnosine -on the doxorubicin induced cardiotoxicity in a rabbit model. For this purpose we evaluated the influence of doxorubicin administration alone and in a combined therapy with carnosine on the haemodynamic parameters and on the degree of cardiac muscle cells alterations in rabbits. The rabbits were divided into four groups. One group of rabbits was injccted with doxorubicin in a dose of 2 mg kg -1 weekly for 7 weeks to induce congestive heart failure. Another group of rabbits received the same doses of doxorubicin simultaneously with carnosine in a dose of 100 mg kg 1 p.o. daily for 9 weeks. Administration of carnosine was started 1 week prior to the first dose of doxorubicin and was ended one week after the administration of the last dose of doxorubicin. The control groups of animals received 0.9% NaCl and carnosine alone. The following haemodynamic parameters were estimated: heart rate, mean arterial pressure, cardiac index, stroke index and total peripheral resistance. Registration of the haemodynamic parameters in rabbits was performed by Doppler method. Carnosine normalised the values of mean arterial pressure in rabbits receiving doxorubicin, and increased the values of cardiac index and stroke index. The influence of carnosine on total peripheral resistance was not statistically significant, but there was a decreasing tendency. The degree of cardiac muscle cell alterations was examined by light microscopy using Mean Total Score technique. The histopathological studies revealed smaller damage of cardiac muscle in rabbits which received doxorubicin and carnosine, in comparison to animals receiving doxorubicin alone. Carnosine seems to be car dioprotective during doxorubicin administration.

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Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract

Cited by 359 publications

References 35 publications

Protective effects of naringenin-7-O-glucoside on doxorubicin-induced apoptosis in H9C2 cells

Protective effects of naringenin-7-O-glucoside on doxorubicin-induced apoptosis in H9C2 cells

The Effect of Grape Seed Proanthocyanidin Extract in Preventing Amikacin-Induced Nephropathy

Effects of Carnosine on the Toxicity of Doxorubicin in Rabbits and Mice

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