Skip to main content
Top
Published in: Cardiovascular Toxicology 1/2011

01-03-2011

Grape Seed Extract Alleviates High-Fat Diet-Induced Obesity and Heart Dysfunction by Preventing Cardiac Siderosis

Authors: Kamel Charradi, Hichem Sebai, Salem Elkahoui, Fethy Ben Hassine, Ferid Limam, Ezzedine Aouani

Published in: Cardiovascular Toxicology | Issue 1/2011

Login to get access

Abstract

Obesity is a tremendous public health problem, characterized by ectopic accumulation of fat into non-adipose tissues, leading to oxidative stress and chronic inflammation, in which the heart is the most severely affected organ. We used an experimental model of high-fat-diet (HFD)-induced obesity to analyze the link between oxidative stress and heart dysfunction. We also studied the cardioprotective effect of a grape seed and skin extract (GSE). Exposure of rats to HFD during 45 days induced heart hypertrophy, inflammation as assessed by plasma CRP elevation and contractile dysfunction as revealed after ischemia/reperfusion of Langendorff-perfused hearts. HFD also induced cardiac steatosis and lipotoxicity, which are linked to an oxidative stress status, worsened by increased siderosis and resulting in Ca2+ overload. Importantly, GSE alleviated all the deleterious effects of HFD treatment. These studies suggest that GSE is a safe anti-obesity and cardioprotective agent that should also find potential applications in other inflammatory damaging conditions as stroke.
Literature
1.
go back to reference Braddon, F. E., Rodgers, B., Wadsworth, M. E., & Davies, J. M. (1986). Onset of obesity in a 36 year birth cohort study. British Medical Journal, 293, 299–303.CrossRefPubMed Braddon, F. E., Rodgers, B., Wadsworth, M. E., & Davies, J. M. (1986). Onset of obesity in a 36 year birth cohort study. British Medical Journal, 293, 299–303.CrossRefPubMed
2.
go back to reference Mokdad, A. H., Ford, E. S., Bowman, B. A., Dietz, W. H., Vinicor, F., Bales, V. S., et al. (2003). Prevalence of obesity, diabetes, and obesity-related health risk factors. JAMA, 289, 76–79.CrossRefPubMed Mokdad, A. H., Ford, E. S., Bowman, B. A., Dietz, W. H., Vinicor, F., Bales, V. S., et al. (2003). Prevalence of obesity, diabetes, and obesity-related health risk factors. JAMA, 289, 76–79.CrossRefPubMed
3.
go back to reference Kopelman, P. G. (2000). Obesity as a medical problem. Nature, 404, 635–643.PubMed Kopelman, P. G. (2000). Obesity as a medical problem. Nature, 404, 635–643.PubMed
4.
go back to reference Unger, R. H., & Orci, L. (2002). Lipoapoptosis: Its mechanism and its diseases. Biochimica et Biophysica Acta, 1585, 202–212.PubMed Unger, R. H., & Orci, L. (2002). Lipoapoptosis: Its mechanism and its diseases. Biochimica et Biophysica Acta, 1585, 202–212.PubMed
5.
go back to reference Zhou, Y. T., Grayburn, P., Karim, A., Shimabukuro, M., Higa, M., Baetens, D., et al. (2000). Lipotoxic heart disease in obese rats: Implications for human obesity. Proceedings of the National Academy of Sciences of the United States of America, 97, 1784–1789.CrossRefPubMed Zhou, Y. T., Grayburn, P., Karim, A., Shimabukuro, M., Higa, M., Baetens, D., et al. (2000). Lipotoxic heart disease in obese rats: Implications for human obesity. Proceedings of the National Academy of Sciences of the United States of America, 97, 1784–1789.CrossRefPubMed
6.
go back to reference Higdon, J. V., & Frei, B. (2003). Obesity and oxidative stress: A direct link to CVD? Arteriosclerosis, Thrombosis, and Vascular Biology, 23, 365.CrossRefPubMed Higdon, J. V., & Frei, B. (2003). Obesity and oxidative stress: A direct link to CVD? Arteriosclerosis, Thrombosis, and Vascular Biology, 23, 365.CrossRefPubMed
7.
go back to reference Katagiri, K., Arakawa, S., Kurahashi, R., & Hatano, Y. (2007). Impaired contact hypersensitivity in diet-induced obese mice. Journal of Dermatological Science, 46, 117–126.CrossRefPubMed Katagiri, K., Arakawa, S., Kurahashi, R., & Hatano, Y. (2007). Impaired contact hypersensitivity in diet-induced obese mice. Journal of Dermatological Science, 46, 117–126.CrossRefPubMed
8.
go back to reference Middleton, E. J., Kandaswami, C., & Theoharides, T. C. (2000). The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer. Pharmacological Reviews, 52, 673–751.PubMed Middleton, E. J., Kandaswami, C., & Theoharides, T. C. (2000). The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer. Pharmacological Reviews, 52, 673–751.PubMed
9.
go back to reference Curin, Y., Ritz, M. F., & Andriantsitohaina, R. (2006). Cellular mechanisms of the protective effect of polyphenols on the neurovascular unit in strokes. Cardiovascular and Hematological Agents in Medical Chemistry, 4, 277–288.CrossRef Curin, Y., Ritz, M. F., & Andriantsitohaina, R. (2006). Cellular mechanisms of the protective effect of polyphenols on the neurovascular unit in strokes. Cardiovascular and Hematological Agents in Medical Chemistry, 4, 277–288.CrossRef
10.
go back to reference Moreno, D. A., Ilic, N., Poulev, A., Brasaemle, D. L., Fried, S. K., & Raskin, I. (2003). Inhibitory effects of grape seed extract on lipases. Nutrition, 19, 876–879.CrossRefPubMed Moreno, D. A., Ilic, N., Poulev, A., Brasaemle, D. L., Fried, S. K., & Raskin, I. (2003). Inhibitory effects of grape seed extract on lipases. Nutrition, 19, 876–879.CrossRefPubMed
11.
go back to reference National Research council. Guide for the care and the use of laboratory animals. (1985). National institute of health, Bethesda, 20, 85–23. National Research council. Guide for the care and the use of laboratory animals. (1985). National institute of health, Bethesda, 20, 85–23.
12.
go back to reference Mokni, M., Limam, F., Elkahoui, S., Amri, M., & Aouani, E. (2007). Strong cardioprotective effect of resveratrol, a red wine polyphenol, on isolated rat hearts after ischemia/reperfusion injury. Archives of Biochemistry and Biophysics, 457, 1–6.CrossRefPubMed Mokni, M., Limam, F., Elkahoui, S., Amri, M., & Aouani, E. (2007). Strong cardioprotective effect of resveratrol, a red wine polyphenol, on isolated rat hearts after ischemia/reperfusion injury. Archives of Biochemistry and Biophysics, 457, 1–6.CrossRefPubMed
13.
go back to reference Hartree, E. F. (1972). Determination of protein: A modification of the Lowry method that gives a linear photometric response. Analytical Biochemistry, 48, 422–427.CrossRefPubMed Hartree, E. F. (1972). Determination of protein: A modification of the Lowry method that gives a linear photometric response. Analytical Biochemistry, 48, 422–427.CrossRefPubMed
14.
go back to reference Folch, J., Lees, M., & Sloane Stanley, G. H. (1957). A simple method for the isolation and purification of total lipids from animal tissues. Journal of Biological Chemistry, 226, 497–509.PubMed Folch, J., Lees, M., & Sloane Stanley, G. H. (1957). A simple method for the isolation and purification of total lipids from animal tissues. Journal of Biological Chemistry, 226, 497–509.PubMed
15.
go back to reference Draper, H. H., & Hadley, M. (1990). Malondialdehyde determination as index of lipid peroxidation. Methods in Enzymology, 186, 421–431.CrossRefPubMed Draper, H. H., & Hadley, M. (1990). Malondialdehyde determination as index of lipid peroxidation. Methods in Enzymology, 186, 421–431.CrossRefPubMed
16.
go back to reference Tietze, F. (1969). Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues. Analytical Biochemistry, 27, 502–522.CrossRefPubMed Tietze, F. (1969). Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues. Analytical Biochemistry, 27, 502–522.CrossRefPubMed
17.
18.
go back to reference Nakamura, K., Hosada, S., & Hayashi, K. (1974). Purification and proprieties of rat liver glutathione peroxidase. Biochimica et Biophysica Acta, 358, 251–261. Nakamura, K., Hosada, S., & Hayashi, K. (1974). Purification and proprieties of rat liver glutathione peroxidase. Biochimica et Biophysica Acta, 358, 251–261.
19.
go back to reference Aebi, H. (1974). Methods of enzymatic analysis, (2nd ed). NewYork: Chemia Weinheium. Aebi, H. (1974). Methods of enzymatic analysis, (2nd ed). NewYork: Chemia Weinheium.
20.
go back to reference Misra, H. P., & Fridovich, I. (1972). The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. Journal of Biological Chemistry, 247, 3170–3175.PubMed Misra, H. P., & Fridovich, I. (1972). The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. Journal of Biological Chemistry, 247, 3170–3175.PubMed
21.
go back to reference Leardi, A., Caraglia, M., Selleri, C., Pepe, S., Pizzi, C., Notaro, R., et al. (1998). Desferioxamine increases iron depletion and apoptosis induced by ara-C of human myeloid leukaemic cells. British Journal Haematology, 102, 746–752.CrossRef Leardi, A., Caraglia, M., Selleri, C., Pepe, S., Pizzi, C., Notaro, R., et al. (1998). Desferioxamine increases iron depletion and apoptosis induced by ara-C of human myeloid leukaemic cells. British Journal Haematology, 102, 746–752.CrossRef
22.
go back to reference Stern, J., & Lewis, W. H. (1957). The colorimetric estimation of calcium in serum with ocresolphthalein complexone. Clinica Chimica Acta, 2, 576–580.CrossRef Stern, J., & Lewis, W. H. (1957). The colorimetric estimation of calcium in serum with ocresolphthalein complexone. Clinica Chimica Acta, 2, 576–580.CrossRef
23.
go back to reference Kakinuma, K., Yamaguchi, T., Kaneda, M., Shimada, K., Tomita, Y., & Chance, B. (1979). A determination of H2O2 release by the treatment of human blood polymorphonuclear leucocytes with myristate. Journal of Biochemistry, 86, 87–95.PubMed Kakinuma, K., Yamaguchi, T., Kaneda, M., Shimada, K., Tomita, Y., & Chance, B. (1979). A determination of H2O2 release by the treatment of human blood polymorphonuclear leucocytes with myristate. Journal of Biochemistry, 86, 87–95.PubMed
24.
go back to reference Petro, A. E., Cotter, J., Cooper, D. A., Peters, J. C., Surwit, S. J., & Surwit, R. S. (2004). Fat, carbohydrate, and calories in the development of diabetes and obesity in the C57BL/6 J mouse. Metabolism, 53, 454–457.CrossRefPubMed Petro, A. E., Cotter, J., Cooper, D. A., Peters, J. C., Surwit, S. J., & Surwit, R. S. (2004). Fat, carbohydrate, and calories in the development of diabetes and obesity in the C57BL/6 J mouse. Metabolism, 53, 454–457.CrossRefPubMed
25.
go back to reference Herskho, C., Link, G., Konijn, A. M., & Cabantchik, Z. I. (2005). Objectives and mechanism of iron chelation therapy. Annals of the New York Academy of Sciences, 1054, 124–135.CrossRef Herskho, C., Link, G., Konijn, A. M., & Cabantchik, Z. I. (2005). Objectives and mechanism of iron chelation therapy. Annals of the New York Academy of Sciences, 1054, 124–135.CrossRef
26.
go back to reference Lecube, A., Carrera, A., Losada, E., Hernández, C., Simó, R., & Mesa, J. (2006). Iron deficiency in obese postmenopausal women. Obesity, 14, 1724–1730.CrossRefPubMed Lecube, A., Carrera, A., Losada, E., Hernández, C., Simó, R., & Mesa, J. (2006). Iron deficiency in obese postmenopausal women. Obesity, 14, 1724–1730.CrossRefPubMed
27.
go back to reference Barbouti, A., Amorgianiotis, C., Kolettas, E., Kanavaros, P., & Galaris, D. (2007). Hydrogen peroxide inhibits caspase-dependent apoptosis by inactivating procaspase-9 in an iron-dependent manner. Free Radical Biology and Medicine, 43, 1377–1387.CrossRefPubMed Barbouti, A., Amorgianiotis, C., Kolettas, E., Kanavaros, P., & Galaris, D. (2007). Hydrogen peroxide inhibits caspase-dependent apoptosis by inactivating procaspase-9 in an iron-dependent manner. Free Radical Biology and Medicine, 43, 1377–1387.CrossRefPubMed
28.
go back to reference Almaguel, F. G., Liu, J. W., Pacheco, F. J., De Leon, D., Casiano, C. A., & De Leon, M. (2010). Lipotoxicity-mediated cell dysfunction and death involve lysosomal membrane permeabilization and cathepsin L activity. Brain Research, 1318, 133–143.CrossRefPubMed Almaguel, F. G., Liu, J. W., Pacheco, F. J., De Leon, D., Casiano, C. A., & De Leon, M. (2010). Lipotoxicity-mediated cell dysfunction and death involve lysosomal membrane permeabilization and cathepsin L activity. Brain Research, 1318, 133–143.CrossRefPubMed
29.
go back to reference Oudit, G. Y., Sun, H., Trivieri, M. G., Koch, S. E., Dawood, F., Ackerley, C., et al. (2003). L-type Ca(2 +) channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy. Nature Medicine, 9, 1187–1194.CrossRefPubMed Oudit, G. Y., Sun, H., Trivieri, M. G., Koch, S. E., Dawood, F., Ackerley, C., et al. (2003). L-type Ca(2 +) channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy. Nature Medicine, 9, 1187–1194.CrossRefPubMed
30.
go back to reference Tsushima, R. G., Wickenden, A. D., Bouchard, R. A., Oudit, G. Y., Liu, P. P., & Backx, P. H. (1999). Modulation of iron uptake in heart by L-type Ca++ channel modifiers: Possible implications in iron overload. Circulation Research, 84, 1302–1309.PubMed Tsushima, R. G., Wickenden, A. D., Bouchard, R. A., Oudit, G. Y., Liu, P. P., & Backx, P. H. (1999). Modulation of iron uptake in heart by L-type Ca++ channel modifiers: Possible implications in iron overload. Circulation Research, 84, 1302–1309.PubMed
31.
go back to reference Fauconnier, J., Anderson, D. C., Zhang, S. J., Lanner, J. T., Wibom, R., Katz, A., et al. (2007). Effects of palmitate on Ca++ handling in adult control and ob/ob cardiomyocytes: Impact of mitochondrial reactive oxygen species. Diabetes, 56, 1136–1142.CrossRefPubMed Fauconnier, J., Anderson, D. C., Zhang, S. J., Lanner, J. T., Wibom, R., Katz, A., et al. (2007). Effects of palmitate on Ca++ handling in adult control and ob/ob cardiomyocytes: Impact of mitochondrial reactive oxygen species. Diabetes, 56, 1136–1142.CrossRefPubMed
32.
go back to reference Haber, F., & Weiss, J. (1934). The catalytic decompensation of hydrogen peroxide by iron salts. Proceedings of the Royal Society of London, 147, 332–351.CrossRef Haber, F., & Weiss, J. (1934). The catalytic decompensation of hydrogen peroxide by iron salts. Proceedings of the Royal Society of London, 147, 332–351.CrossRef
33.
go back to reference Ishii, M., Shimizu, S., Hara, Y., Hagiwara, T., Miyazaki, A., Mori, Y., et al. (2006). Intracellular-produced hydroxyl radical mediates H2O2-induced Ca2+ influx and cell death in rat beta-cell line RIN-5F. Cell Calcium, 39, 487–494.CrossRefPubMed Ishii, M., Shimizu, S., Hara, Y., Hagiwara, T., Miyazaki, A., Mori, Y., et al. (2006). Intracellular-produced hydroxyl radical mediates H2O2-induced Ca2+ influx and cell death in rat beta-cell line RIN-5F. Cell Calcium, 39, 487–494.CrossRefPubMed
34.
go back to reference Jang, H. J., Nde, C., Toghrol, F., & Bentley, W. E. (2009). Microarray analysis of Mycobacterium bovis BCG revealed induction of iron acquisition related genes in response to hydrogen peroxide. Environmental Science and Technology, 43, 9465–9472.CrossRefPubMed Jang, H. J., Nde, C., Toghrol, F., & Bentley, W. E. (2009). Microarray analysis of Mycobacterium bovis BCG revealed induction of iron acquisition related genes in response to hydrogen peroxide. Environmental Science and Technology, 43, 9465–9472.CrossRefPubMed
35.
go back to reference Srivastava, S., Chandrasekar, B., Gu, Y., Luo, J., Hamid, T., Hill, B. G., et al. (2007). Downregulation of CuZn-superoxide dismutase contributes to beta-adrenergic receptor-mediated oxidative stress in the heart. Cardiovascular Research, 74, 445–455.CrossRefPubMed Srivastava, S., Chandrasekar, B., Gu, Y., Luo, J., Hamid, T., Hill, B. G., et al. (2007). Downregulation of CuZn-superoxide dismutase contributes to beta-adrenergic receptor-mediated oxidative stress in the heart. Cardiovascular Research, 74, 445–455.CrossRefPubMed
36.
go back to reference Yamakura, F., Kobayashi, K., Furukawa, S., & Suzuki, Y. (2007). In vitro preparation of iron-substituted human manganese superoxide dismutase: Possible toxic properties for mitochondria. Free Radical Biology and Medicine, 43, 423–430.CrossRefPubMed Yamakura, F., Kobayashi, K., Furukawa, S., & Suzuki, Y. (2007). In vitro preparation of iron-substituted human manganese superoxide dismutase: Possible toxic properties for mitochondria. Free Radical Biology and Medicine, 43, 423–430.CrossRefPubMed
37.
go back to reference Heck, D. E., Vetrano, A. M., Marano, T. M., & Laskin, J. D. (2003). UVB light stimulates production of reactive oxygen species: Unexpected role for catalase. J Biol Chem, 278, 22432–22436.CrossRefPubMed Heck, D. E., Vetrano, A. M., Marano, T. M., & Laskin, J. D. (2003). UVB light stimulates production of reactive oxygen species: Unexpected role for catalase. J Biol Chem, 278, 22432–22436.CrossRefPubMed
38.
go back to reference Yamakura, F., & Kawasaki, H. (2009). Post-translational modifications of superoxide dismutase. Biochimica et Biophysica Acta, 1804, 318–325.PubMed Yamakura, F., & Kawasaki, H. (2009). Post-translational modifications of superoxide dismutase. Biochimica et Biophysica Acta, 1804, 318–325.PubMed
39.
go back to reference Sugiyama, H., Ahazome, Y., Shojit, T., Yaamaguchi, A., Yasne, M., Kanda, T., et al. (2007). Oligomeric procyanidins in apple polyphenol are main active components for inhibition of pancreatic lipase and triglyceride absorption. Journal of Agriculture and Food Chemistry, 55, 4604–4609.CrossRef Sugiyama, H., Ahazome, Y., Shojit, T., Yaamaguchi, A., Yasne, M., Kanda, T., et al. (2007). Oligomeric procyanidins in apple polyphenol are main active components for inhibition of pancreatic lipase and triglyceride absorption. Journal of Agriculture and Food Chemistry, 55, 4604–4609.CrossRef
40.
go back to reference Richmond, S. R., Carper, M. J., Lei, X., Zhang, S., Yarasheski, K. E., & Ramanadham, S. (2010). HIV-protease inhibitors suppress skeletal muscle fatty acid oxidation by reducing CD36 and CPT1 fatty acid transporters. Biochimica et Biophysica Acta, 1801, 559–566.PubMed Richmond, S. R., Carper, M. J., Lei, X., Zhang, S., Yarasheski, K. E., & Ramanadham, S. (2010). HIV-protease inhibitors suppress skeletal muscle fatty acid oxidation by reducing CD36 and CPT1 fatty acid transporters. Biochimica et Biophysica Acta, 1801, 559–566.PubMed
41.
go back to reference Oudit, G. Y., Trivieri, M. G., Khaper, N., Liu, P. P., & Backx, P. H. (2006). Role of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy. Journal of Molecular Medicine, 84, 349–364.CrossRefPubMed Oudit, G. Y., Trivieri, M. G., Khaper, N., Liu, P. P., & Backx, P. H. (2006). Role of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy. Journal of Molecular Medicine, 84, 349–364.CrossRefPubMed
42.
go back to reference Alcocer, L., Bendersky, M., Acosta, J., & Urina-Triana, M. (2010). Use of calcium channel blockers (CCB) in cardiovascular risk reduction: Issues in Latin America. American Journal of Cardiovascular Drugs, 10, 143–154.CrossRefPubMed Alcocer, L., Bendersky, M., Acosta, J., & Urina-Triana, M. (2010). Use of calcium channel blockers (CCB) in cardiovascular risk reduction: Issues in Latin America. American Journal of Cardiovascular Drugs, 10, 143–154.CrossRefPubMed
43.
go back to reference Tang, S. C., Lathia, J. D., Selvaraj, P. K., Jo, D. G., Mughal, M. R., Cheng, A., et al. (2008). Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid β-peptide and the membrane lipid peroxidation product 4-hydroxynonenal. Experimental Neurology, 213, 114–121.CrossRefPubMed Tang, S. C., Lathia, J. D., Selvaraj, P. K., Jo, D. G., Mughal, M. R., Cheng, A., et al. (2008). Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid β-peptide and the membrane lipid peroxidation product 4-hydroxynonenal. Experimental Neurology, 213, 114–121.CrossRefPubMed
44.
go back to reference Folden, D. V., Gupta, A., Sharma, A. C., Li, S. Y., Saari, J. T., & Ren, J. (2009). Malondialdehyde inhibits cardiac contractile function in ventricular myocytes via a p38 mitogen-activated protein kinase-dependent mechanism. British Journal of Pharmacology, 139, 1310–1316.CrossRef Folden, D. V., Gupta, A., Sharma, A. C., Li, S. Y., Saari, J. T., & Ren, J. (2009). Malondialdehyde inhibits cardiac contractile function in ventricular myocytes via a p38 mitogen-activated protein kinase-dependent mechanism. British Journal of Pharmacology, 139, 1310–1316.CrossRef
45.
go back to reference Sebai, H., Ristorcelli, E., Sbarra, V., Hovsepian, S., Fayet, G., Aouani, E., et al. (2010). Protective effect of resveratrol against LPS-induced extracellular lipoperoxidation in AR42 J cells partly via a Myd88-dependent signaling pathway. Archives of Biochemistry and Biophysics, 495, 56–61.CrossRefPubMed Sebai, H., Ristorcelli, E., Sbarra, V., Hovsepian, S., Fayet, G., Aouani, E., et al. (2010). Protective effect of resveratrol against LPS-induced extracellular lipoperoxidation in AR42 J cells partly via a Myd88-dependent signaling pathway. Archives of Biochemistry and Biophysics, 495, 56–61.CrossRefPubMed
46.
go back to reference Lu, C., Chan, S. L., Fu, W., & Mattson, M. P. (2002). The lipid peroxidation product 4-hydroxynonenal facilitates opening of voltage dependent calcium channels in neurons by increasing protein tyrosine phosphorylation. Journal of Biological Chemistry, 277, 24368–24375.CrossRefPubMed Lu, C., Chan, S. L., Fu, W., & Mattson, M. P. (2002). The lipid peroxidation product 4-hydroxynonenal facilitates opening of voltage dependent calcium channels in neurons by increasing protein tyrosine phosphorylation. Journal of Biological Chemistry, 277, 24368–24375.CrossRefPubMed
47.
go back to reference Nakamura, K., Miura, D., Kusano, K. F., Fujimoto, Y., Yoshikawa, W. S., Fuke, S., et al. (2009). 4 Hydroxy-2-nonenal induces calcium overload via the generation of reactive oxygene species in isolated rat cardiac myocytes. Journal of Cardiac Failure, 15, 709–716.CrossRefPubMed Nakamura, K., Miura, D., Kusano, K. F., Fujimoto, Y., Yoshikawa, W. S., Fuke, S., et al. (2009). 4 Hydroxy-2-nonenal induces calcium overload via the generation of reactive oxygene species in isolated rat cardiac myocytes. Journal of Cardiac Failure, 15, 709–716.CrossRefPubMed
48.
go back to reference Pepys, M. B., Hirschfield, G. M., Tennent, G. A., Gallimore, J. R., Kahan, M. C., Bellotti, V., et al. (2006). Targeting C-reactive protein for the treatment of cardiovascular disease. Nature, 440, 1217–1221.CrossRefPubMed Pepys, M. B., Hirschfield, G. M., Tennent, G. A., Gallimore, J. R., Kahan, M. C., Bellotti, V., et al. (2006). Targeting C-reactive protein for the treatment of cardiovascular disease. Nature, 440, 1217–1221.CrossRefPubMed
49.
go back to reference Bagchi, D., Bagchi, M., Stohs, S. J., Das, D. K., Ray, S. D., Kuszynski, C. A., et al. (2000). Free radicals and grape seed proanthocyanidin extract: Importance in human health and disease prevention. Toxicology, 148, 187–197.CrossRefPubMed Bagchi, D., Bagchi, M., Stohs, S. J., Das, D. K., Ray, S. D., Kuszynski, C. A., et al. (2000). Free radicals and grape seed proanthocyanidin extract: Importance in human health and disease prevention. Toxicology, 148, 187–197.CrossRefPubMed
50.
go back to reference Isoda, M., Hanawa, H., Watanabe, R., Yoshida, T., Toba, K., Yoshida, K., et al. (2010). Expression of the peptide hormone hepcidin increases in cardiomyocytes under myocarditis and myocardial infarction. The Journal of Nutritional Biochemistry, 21, 749–756.CrossRefPubMed Isoda, M., Hanawa, H., Watanabe, R., Yoshida, T., Toba, K., Yoshida, K., et al. (2010). Expression of the peptide hormone hepcidin increases in cardiomyocytes under myocarditis and myocardial infarction. The Journal of Nutritional Biochemistry, 21, 749–756.CrossRefPubMed
Metadata
Title
Grape Seed Extract Alleviates High-Fat Diet-Induced Obesity and Heart Dysfunction by Preventing Cardiac Siderosis
Authors
Kamel Charradi
Hichem Sebai
Salem Elkahoui
Fethy Ben Hassine
Ferid Limam
Ezzedine Aouani
Publication date
01-03-2011
Publisher
Humana Press Inc
Published in
Cardiovascular Toxicology / Issue 1/2011
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-010-9101-z

Other articles of this Issue 1/2011

Cardiovascular Toxicology 1/2011 Go to the issue