Oligomerized grape seed proanthocyanidins ameliorates isoproterenol-induced cardiac remodeling in rats: role of oxidative stress

Matrix metalloproteinases (MMPs), activated by oxidative stress, play a key role during cardiac remodeling. In the present study we aimed to assess the role of MMPs in experimental cardiomyopathy induced by repeated 10-week administration of daunorubicin (3 mg/kg i.v.) to rabbits. In the daunorubicin group, the plasma cardiac troponin T levels (cTnT – a marker of myocardial necrosis) were significantly increased (p<0.05), commencing with the 8th administration compared with the controls. The amount of collagen (an estimate of fibrosis) was also significantly higher in the daunorubicin group (13.39 ± 0.97 mg/g wet weight) compared to the control group (10.03 ± 0.65 mg/g wet weight). In both groups, the LV MMP-activity was observed only in the gelatine substrate in the 70 kDa region (MMP-2), while no MMPs activities were detectable either in the casein or collagen containing zymograms. At the end of the experiment, the MMP- 2 activity was slightly up-regulated (by 16 %) compared with the controls.

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Protective Role of Grape Seed Proanthocyanidins Against Ccl4 Induced Acute Liver Injury in Mice

Medical Science Monitor ◽

10.12659/msm.895552 ◽

2016 ◽

Vol 22 ◽

pp. 880-889 ◽

Cited By ~ 9

Author(s):

Jinfa Zou ◽

Fengjie Qi ◽

Liping Ye ◽

Suyan Yao

Keyword(s):

Liver Injury ◽

Acute Liver Injury ◽

Grape Seed ◽

Protective Role ◽

Grape Seed Proanthocyanidins

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Abstract 1271: IKKβ/NF-κB Pathway Protects Hearts from Hemodynamic Stress Mediated through Regulating MnSOD Expression

Circulation ◽

10.1161/circ.116.suppl_16.ii_259-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Shungo Hikoso ◽

Kinya Otsu ◽

Osamu Yamaguchi ◽

Toshihiro Takeda ◽

Masayuki Taniike ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Cardiac Remodeling ◽

Weight Ratio ◽

Pressure Overload ◽

Left Ventricular ◽

Negative Regulator ◽

Iκb Kinase ◽

Jnk Activation

Objectives: We have previously reported that NF-κB contributes to GPCR agonist-induced hypertrophy in cultured cardiomyocytes. However, the in vivo role of this pathway in the pathogenesis of cardiac remodeling remains to be elucidated. Although IκB kinase β (IKKβ)/NF-κB pathway is a major negative regulator of cell death, it can sensitize cells to death-inducing stimuli in some instances, thus it can be either anti- or pro-apoptotic. In this study, we aimed to clarify the role of IKKβ/NF-κB signaling in cardiac remodeling using cardiac-specific IKKβ deficient mice. Methods and Results: We crossed mice bearing an IKK β flox allele with mice expressing the Cre recombinase under the control of the myosin light chain 2v promoter ( MLC2v-Cre +/− ) to generate IKK β flox/flox ; MLC2v-Cre +/− mice (conditional knockout:CKO). Then, CKO mice (n=14) and control littermates bearing IKK β flox/flox (CTRL, n=14) were subjected to pressure overload by means of transverse aortic constriction (TAC). EMSA analysis revealed NF-κB DNA binding activity after TAC had attenuated in CKO hearts. One week after TAC, echocardiography showed significantly lower left ventricular fractional shortening (26.9±2.7% vs. 41.4±0.9%, p<0.01), and higher left ventricular end-diastolic dimension (4.02±0.14 mm vs. 3.47±0.08 mm, p<0.01) and lung weight/body weight ratio (11.1±1.4 vs. 5.5±0.1, p<0.01) in CKO mice compared with CTRL mice, indicating the development of heart failure in CKO mice. Number of apoptotic cells had increased in CKO hearts after TAC, suggesting that the enhanced apoptosis is a cause for heart failure. The expression levels of MnSOD mRNA and protein after TAC, which is one of NF-κB target genes, were significantly lower in CKO than those in CTRL mice. As a consequence, oxidative stress and JNK activation in CKO hearts after TAC had significantly increased compared with those in CTRL heart, suggesting that increased oxidative stress and enhanced JNK activity resulted in cardiomyocyte apoptosis in CKO hearts. Conclusion: These results show that IKKβ/NF-κB pathway in cardiomyocyte plays a protective role mediated through attenuation of oxidative stress and JNK activation in response to pressure overload.

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Neurotoxicity and neuroinflammatory effects of bisphenol A in male rats: the neuroprotective role of grape seed proanthocyanidins

Environmental Science and Pollution Research ◽

10.1007/s11356-021-16311-1 ◽

2021 ◽

Author(s):

Heba M. Abdou ◽

Heba-Tallah Abd Elrahim Abd Elkader ◽

Amel H. El-Gendy ◽

Saber Mohamed Eweda

Keyword(s):

Bisphenol A ◽

Grape Seed ◽

Male Rats ◽

Grape Seed Proanthocyanidins

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P6283Downregulation of Tim44 exacerbates oxidative stress-induced ROS production and cardiomyocytes death by reducing mitochondrial SOD2

European Heart Journal ◽

10.1093/eurheartj/ehz746.0881 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

S Ikeda ◽

S Matsushima ◽

K Okabe ◽

A Ishikita ◽

T Tadokoro ◽

...

Keyword(s):

Oxidative Stress ◽

Cardiac Remodeling ◽

Protein Import ◽

Mitochondrial Fraction ◽

Left Ventricular ◽

Protein Carbonylation ◽

Neonatal Rat ◽

Ros Production ◽

Protein Levels

Abstract Background Mitochondrial dysfunction has been highlighted as a critical driver of cardiac remodeling and failure. Mitochondria contains about 1500 proteins, 99% of which are encoded in the nuclear genome. Therefore, protein import into mitochondria is essential to maintain mitochondrial function. Previous reports suggest that nuclear-encoded mitochondrial precursor proteins import into mitochondria by multiple complex; translocase of outer membrane (TOM), translocase of inner membrane (TIM), and protein associated motor (PAM). However, the role of these protein import machineries of mitochondria in cardiac remodeling remains to be elucidated. Objective The purpose of this study was to elucidate the role of TOM, TIM, and PAM complex in cardiac remodeling and cardiomyocyte death. Methods and results C57BL/6J mice were subjected to myocardial infarction (MI) by permanent ligation of left anterior descending artery. Four weeks after operation, MI-mice demonstrated left ventricular (LV) dilation (LV end-diastolic dimension: 3.91 vs. 5.54 mm, n=8–11, p<0.05) and dysfunction (LV fractional shortening: 33.3 vs. 7.7%, n=8–11, p<0.05). Tim44 protein levels, a component of PAM complex, in mitochondrial fraction from non-infarcted left ventricle were significantly decreased compared with those in the heart from sham-operated mice by 39% (p<0.05), whereas other proteins related to TOM, TIM and PAM complex such as Tom20, Tom22, Tom40, Tom70, Tim22, Tim23 and mtHSP70 were not altered between MI-mice and sham-mice. In addition, blue-native polyacrylamide gel electrophoresis revealed that a protein complex associated to Tim44 was significantly decreased in non-infarcted LV by 40% (p<0.05). Superoxide dismutase 2 (SOD2), a mitochondrial matrix protein, was decreased in mitochondrial fraction from non-infarcted LV by 20% (p<0.05), accompanied by enhancing protein carbonylation, a marker of oxidative stress, by 40% (p<0.05). To assess the role of Tim44, it was downregulated by small interfering RNA in cultured neonatal rat ventricular myocytes (NRVMs). Knockdown of Tim44 significantly decreased SOD2 protein levels in mitochondrial fractionation (22%, p<0.05), with no significant changes in its mRNA levels. Furthermore, knockdown of Tim44 significantly increased protein carbonylation (20%, p<0.05) and cleaved caspase 3 (47%, p<0.05) and decreased cell viability (69%, p<0.05), assessed by cell titer assay, in H2O2-treatred NRVMs. Conclusions Downregulation of Tim44 exacerbates oxidative stress-induced ROS production and cardiomyocytes death, which is associated with a decrease in mitochondrial SOD2. Endogenous Tim44 might play a protective role in cardiac remodeling by attenuating oxidative stress and cardiomyocyte death via SOD2 import into mitochondria.

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