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Erschienen in: Cardiovascular Drugs and Therapy 4/2008

01.08.2008

Effects of Folic Acid on Cardiac Myocyte Apoptosis in Rats with Streptozotocin-induced Diabetes Mellitus

verfasst von: Tong-Guo Wu, Wei-Hong Li, Zi-Qing Lin, Le-Xin Wang

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 4/2008

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Abstract

Backgrounds

The effect of folic acid on cardiac myocyte apoptosis secondary to diabetes is unknown.

Methods

Diabetic rats were divided into diabetic control (DC, n = 11), low-dose (LDF, 0.4 mg/kg/day, n = 12) and high-dose (HDF, 1.2 mg/kg/day, n = 12) folic acid groups. Non-diabetic rats (n = 11) were used as the normal control (NC).

Results

After 11 weeks of treatment, compared with the NC group, the DC group showed a reduced blood levels of reactive oxygen species (ROS, P < 0.01). The rate of cardiac myocyte apoptosis in the diabetic control group was also greater than in the non-diabetic control group (P < 0.01). In folic acid-treated rats, the blood levels of ROS was higher than in the diabetic control group (P < 0.05). There was a dose-dependent reduction in the rate of cardiac myocyte apoptosis in the folic acid groups (P < 0.01), and this was accompanied by an increased level of anti-apoptotic protein Bcl-2 and decreased level of pro-apoptotic protein Bax and Fas (P < 0.01).

Conclusions

Dietary folic acid supplementation diminishes the cardiac myocyte apoptosis in streptozotocin-induced diabetes. The apoptosis suppression is accompanied by an increase in the expression of Bcl-2 and a decrease in Bax and Fas.
Literatur
1.
Zurück zum Zitat Galderisi M, Anderson KM, Wilson PW, Levy D. Echocardiographic evidence for the existence of a distinct diabetic cardiomyopathy (the Framingham Heart Study). Am J Cardiol. 1991;68:85–9.PubMedCrossRef Galderisi M, Anderson KM, Wilson PW, Levy D. Echocardiographic evidence for the existence of a distinct diabetic cardiomyopathy (the Framingham Heart Study). Am J Cardiol. 1991;68:85–9.PubMedCrossRef
2.
Zurück zum Zitat An D, Rodrigues B. Role of changes in cardiac metabolism in development of diabetic cardiomyopathy. Am J Physiol—Heart Circ Physiol. 2006;291:H1489–506.PubMedCrossRef An D, Rodrigues B. Role of changes in cardiac metabolism in development of diabetic cardiomyopathy. Am J Physiol—Heart Circ Physiol. 2006;291:H1489–506.PubMedCrossRef
3.
Zurück zum Zitat Fiordaliso F, Li B, Latini R, Sonnenblick EH, Anversa P, Leri A, Kajstura J. Myocytes death in streptozotocin-induced diabetes in rats is angiotensin II-dependent. Lab Invest. 2000;80:513–27.PubMed Fiordaliso F, Li B, Latini R, Sonnenblick EH, Anversa P, Leri A, Kajstura J. Myocytes death in streptozotocin-induced diabetes in rats is angiotensin II-dependent. Lab Invest. 2000;80:513–27.PubMed
4.
Zurück zum Zitat Kajstura J, Fiordaliso F, Andreoli AM, Li B, Chimenti S, Medow MS, Limana F, Nadal-Ginard B, Leri A, Anversa P. IGF-1 overexpression inhibits the development of diabetic cardiomyopathy and angiotensin II-mediated oxidative stress. Diabetes 2001;50:1414–24.PubMedCrossRef Kajstura J, Fiordaliso F, Andreoli AM, Li B, Chimenti S, Medow MS, Limana F, Nadal-Ginard B, Leri A, Anversa P. IGF-1 overexpression inhibits the development of diabetic cardiomyopathy and angiotensin II-mediated oxidative stress. Diabetes 2001;50:1414–24.PubMedCrossRef
5.
Zurück zum Zitat Frustaci A, Kajstura J, Chimenti C, Jakoniuk I, Len A, Maseri A, Nadal-Ginard B, Anversa P. Myocardial cell death in human diabetes. Circ Res. 2000;87:1123–32.PubMed Frustaci A, Kajstura J, Chimenti C, Jakoniuk I, Len A, Maseri A, Nadal-Ginard B, Anversa P. Myocardial cell death in human diabetes. Circ Res. 2000;87:1123–32.PubMed
6.
Zurück zum Zitat Mangoni AA, Sherwood RA, Asonganyi B, Swift CG, Thomas S, Jackson SH. Short-term oral folic acid supplementation enhances endothelial function in patients with type 2 diabetes. Am J Hyperten. 2005;18:220–6.CrossRef Mangoni AA, Sherwood RA, Asonganyi B, Swift CG, Thomas S, Jackson SH. Short-term oral folic acid supplementation enhances endothelial function in patients with type 2 diabetes. Am J Hyperten. 2005;18:220–6.CrossRef
7.
Zurück zum Zitat Gareskog M, Eriksson UJ, Wetzel P. Combined supplementation of folic acid and vitamin E diminishes diabetes-induced embryotoxicity in rats. Birth Defects Res. 2006;76:483–90.CrossRef Gareskog M, Eriksson UJ, Wetzel P. Combined supplementation of folic acid and vitamin E diminishes diabetes-induced embryotoxicity in rats. Birth Defects Res. 2006;76:483–90.CrossRef
8.
Zurück zum Zitat Craciunescu CN, Brown EC, Mar MH, Albright CD, Nadeau MR, Zeisel SH. Folic acid deficiency during late gestation decreases progenitor cell proliferation and increases apoptosis in fetal mouse brain. J Nutr. 2004;134:162–6.PubMed Craciunescu CN, Brown EC, Mar MH, Albright CD, Nadeau MR, Zeisel SH. Folic acid deficiency during late gestation decreases progenitor cell proliferation and increases apoptosis in fetal mouse brain. J Nutr. 2004;134:162–6.PubMed
9.
Zurück zum Zitat Lin HL, Chen CJ, Tsai WC, Yen JH, Liu HW. In vitro folate deficiency induces apoptosis by a p53, Fas (Apo-1, CD95) independent, bcl-2 related mechanism in phytohaemagglutinin-stimulated human peripheral blood lymphocytes. Br J Nutr. 2006;95:870–8.PubMedCrossRef Lin HL, Chen CJ, Tsai WC, Yen JH, Liu HW. In vitro folate deficiency induces apoptosis by a p53, Fas (Apo-1, CD95) independent, bcl-2 related mechanism in phytohaemagglutinin-stimulated human peripheral blood lymphocytes. Br J Nutr. 2006;95:870–8.PubMedCrossRef
10.
Zurück zum Zitat Chern CL, Huang RF, Chen YH, Cheng JT, Liu TZ. Folate deficiency-induced oxidative stress and apoptosis are mediated via homocysteine-dependent overproduction of hydrogen peroxide and enhanced activation of NF-kappaB in human Hep G2 cells. Biomed Pharmacother. 2001;55:434–42.PubMedCrossRef Chern CL, Huang RF, Chen YH, Cheng JT, Liu TZ. Folate deficiency-induced oxidative stress and apoptosis are mediated via homocysteine-dependent overproduction of hydrogen peroxide and enhanced activation of NF-kappaB in human Hep G2 cells. Biomed Pharmacother. 2001;55:434–42.PubMedCrossRef
11.
Zurück zum Zitat Berkels R, Purol-Schnabel S, Roesen R. A new method to measure nitrate/nitrite with a NO-sensitive electrode. J Appl Physiol. 2001;90:317–20.PubMed Berkels R, Purol-Schnabel S, Roesen R. A new method to measure nitrate/nitrite with a NO-sensitive electrode. J Appl Physiol. 2001;90:317–20.PubMed
12.
Zurück zum Zitat Durak I, Yurtarslanl Z, Canbolat O, Akyol O. A methodological approach to superoxide dismutase (SOD) activity assay based on inhibition of nitroblue tetrazolium (NBT) reduction. Clin Chim Acta. 1993;214:103–4.PubMedCrossRef Durak I, Yurtarslanl Z, Canbolat O, Akyol O. A methodological approach to superoxide dismutase (SOD) activity assay based on inhibition of nitroblue tetrazolium (NBT) reduction. Clin Chim Acta. 1993;214:103–4.PubMedCrossRef
13.
Zurück zum Zitat Draper HH, Hadley M. Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol. 1990;186:421–31.PubMedCrossRef Draper HH, Hadley M. Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol. 1990;186:421–31.PubMedCrossRef
14.
Zurück zum Zitat Dandona P, Thusu K, Cook S, Snyder B, Makowski J, Armstrong D, Nicotera T. Oxidative damage to DNA in diabetes mellitus. Lancet 1996;347:444–5.PubMedCrossRef Dandona P, Thusu K, Cook S, Snyder B, Makowski J, Armstrong D, Nicotera T. Oxidative damage to DNA in diabetes mellitus. Lancet 1996;347:444–5.PubMedCrossRef
15.
Zurück zum Zitat Tanaka Y, Gleason CE, Tran PO, Harmon JS, Robertson RP. Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants. Proc Natl Acad Sci. 1999;96:10857–62.PubMedCrossRef Tanaka Y, Gleason CE, Tran PO, Harmon JS, Robertson RP. Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants. Proc Natl Acad Sci. 1999;96:10857–62.PubMedCrossRef
16.
Zurück zum Zitat Berry C, Hamilton CA, Brosnan MJ, Magill FG, Berg GA, McMurray JJ, Dominiczak AF. Investigation into the sources of superoxide in human blood vessels: angiotensin II increases superoxide production in human internal mammary arteries. Circulation 2000;101:2206–12.PubMed Berry C, Hamilton CA, Brosnan MJ, Magill FG, Berg GA, McMurray JJ, Dominiczak AF. Investigation into the sources of superoxide in human blood vessels: angiotensin II increases superoxide production in human internal mammary arteries. Circulation 2000;101:2206–12.PubMed
17.
Zurück zum Zitat Fiordaliso F, De Angelis N, Bai A, Cuccovillo I, Salio M, Maria Serra D, Bianchi R, Razzetti R, Latini R, Masson S. Effect of beta-adrenergic and renin–angiotensin system blockade on myocyte apoptosis and oxidative stress in diabetic hypertensive rats. Life Sci. 2007;81:951–9.PubMedCrossRef Fiordaliso F, De Angelis N, Bai A, Cuccovillo I, Salio M, Maria Serra D, Bianchi R, Razzetti R, Latini R, Masson S. Effect of beta-adrenergic and renin–angiotensin system blockade on myocyte apoptosis and oxidative stress in diabetic hypertensive rats. Life Sci. 2007;81:951–9.PubMedCrossRef
18.
Zurück zum Zitat Jones WK, Flaherty MP, Tang XL, Takano H, Qiu Y, Banerjee S, Smith T, Bolli R. Ischemic preconditioning increases iNOS transcript levels in conscious rabbits via a nitric oxide-dependent mechanism. J Mol Cell Cardiol. 1999;31:1469–81.PubMedCrossRef Jones WK, Flaherty MP, Tang XL, Takano H, Qiu Y, Banerjee S, Smith T, Bolli R. Ischemic preconditioning increases iNOS transcript levels in conscious rabbits via a nitric oxide-dependent mechanism. J Mol Cell Cardiol. 1999;31:1469–81.PubMedCrossRef
19.
Zurück zum Zitat Adeghate E. Molecular and cellular basis of the aetiology and management of diabetic cardiomyopathy: a short review. Mol Cell Biochem. 2004;261:187–91.PubMedCrossRef Adeghate E. Molecular and cellular basis of the aetiology and management of diabetic cardiomyopathy: a short review. Mol Cell Biochem. 2004;261:187–91.PubMedCrossRef
20.
Zurück zum Zitat Del Poeta G, Venditti A, Del Principe MI, Maurillo L, Buccisano F, Tamburini A, Cox MC, Franchi A, Bruno A, Mazzone C, Panetta P, Suppo G, Masi M, Amadori S. Amount of spontaneous apoptosis detected by bax/bcl-2 ratio predicts outcome in acute myeloid leukemia (AML). Blood 2003;101:2125–31.PubMedCrossRef Del Poeta G, Venditti A, Del Principe MI, Maurillo L, Buccisano F, Tamburini A, Cox MC, Franchi A, Bruno A, Mazzone C, Panetta P, Suppo G, Masi M, Amadori S. Amount of spontaneous apoptosis detected by bax/bcl-2 ratio predicts outcome in acute myeloid leukemia (AML). Blood 2003;101:2125–31.PubMedCrossRef
21.
Zurück zum Zitat Chinnaiyan AM, O’Rourke K, Tewari M, Dixit VM. FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 1995;81:505–12.PubMedCrossRef Chinnaiyan AM, O’Rourke K, Tewari M, Dixit VM. FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 1995;81:505–12.PubMedCrossRef
22.
Zurück zum Zitat Huang RF, Yaong HC, Chen SC, Lu YF. In vitro folate supplementation alleviates oxidative stress, mitochondria-associated death signaling and apoptosis induced by 7-ketocholesterol. Br J Nutr. 2004;92:887–94.PubMedCrossRef Huang RF, Yaong HC, Chen SC, Lu YF. In vitro folate supplementation alleviates oxidative stress, mitochondria-associated death signaling and apoptosis induced by 7-ketocholesterol. Br J Nutr. 2004;92:887–94.PubMedCrossRef
23.
Zurück zum Zitat Paolisso G, Tataranni PA, Foley JE, Bogardus C, Howard BV, Ravussin E. A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM. Diabetologia 1995;38:1213–7.PubMedCrossRef Paolisso G, Tataranni PA, Foley JE, Bogardus C, Howard BV, Ravussin E. A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM. Diabetologia 1995;38:1213–7.PubMedCrossRef
24.
Zurück zum Zitat Cnop M, Hannaert JC, Hoorens A, Eizirik DL, Pipeleers DG. Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation. Diabetes 2001;50:1771–7.PubMedCrossRef Cnop M, Hannaert JC, Hoorens A, Eizirik DL, Pipeleers DG. Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation. Diabetes 2001;50:1771–7.PubMedCrossRef
25.
Zurück zum Zitat Artwohl M, Roden M, Waldhausl W, Freudenthaler A, Baumgartner-Parzer SM. Free fatty acids trigger apoptosis and inhibit cell cycle progression in human vascular endothelial cells. FASEB J. 2004;18:146–8.PubMed Artwohl M, Roden M, Waldhausl W, Freudenthaler A, Baumgartner-Parzer SM. Free fatty acids trigger apoptosis and inhibit cell cycle progression in human vascular endothelial cells. FASEB J. 2004;18:146–8.PubMed
26.
Zurück zum Zitat Bitar MS. Co-administration of etomoxir and RU-486 mitigates insulin resistance in hepatic and muscular tissues of STZ-induced diabetic rats. Horm Metab Res. 2001;33:577–84.PubMedCrossRef Bitar MS. Co-administration of etomoxir and RU-486 mitigates insulin resistance in hepatic and muscular tissues of STZ-induced diabetic rats. Horm Metab Res. 2001;33:577–84.PubMedCrossRef
Metadaten
Titel
Effects of Folic Acid on Cardiac Myocyte Apoptosis in Rats with Streptozotocin-induced Diabetes Mellitus
verfasst von
Tong-Guo Wu
Wei-Hong Li
Zi-Qing Lin
Le-Xin Wang
Publikationsdatum
01.08.2008
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 4/2008
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-008-6109-8

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