Effects of L-Carnitine on Cardiac Apoptosis in Ischemic-Reperfused Isolated Rat Heart L-carnitine and apoptosis
Iranian Journal of Pharmaceutical Sciences,
Vol. 3 No. 1 (2007),
15 January 2007
,
Page 19-24
https://doi.org/10.22037/ijps.v3.40330
Abstract
Carnitine is a vital biologic substance for transporting fatty acids into myocytes.It also facilitates fatty acids β-oxidation for energy production. In this study, effectsof L-carnitine (L-Car) on apoptosis in the ischemic isolated rat heart were investigated.Male Sprague-Dawley rats were divided into four groups and anesthetized bysodium pentobarbital. The heart was removed and mounted on a Langendorffapparatus then perfused by a modified Krebs-Henseleit (K/H) solution under aconstant pressure at 37 °C. In the control group, the hearts were perfused only bynormal K/H solution at stabilization, 30 min. regional ischemia and 120 min.reperfusion, while in each of the test groups, the hearts were perfused duringischemia-reperfusion with 0.5, 2.5 and 5 mM of L-Car-enriched K/H solution,respectively. At the end of reperfusion, immunohistochemical detection of apoptoticcells was performed by using an in situapoptosis detection kit. The number ofTUNEL-positive cardiomyocytes was counted in five random high-power fields ineach sample. In the control group, the number of apoptotic cells were 48±3 whileaddition of L-Car (0.5, 2.5 and 5 mM) to the solution reduced the number ofapoptotic cells to 6±1, 4±1 and 3±1, respectively (p<0.001 for all concentrations).There was no significant difference between and within test groups using ANOVAone-way. Considering these results, we conclude that L-Car has a protective effectagainst cardiac ischemia-reperfusion induced injuries as a reduction of apoptoticcardiomyocytes.
- Apoptosis
- Isolated heart
- L-Carnitine
- Rat
How to Cite
References
[2]Ford DA. Alterations in myocardial lipidmetabolism during myocardial ischemia andreperfusion. Prog Lipid Res2002; 41: 6-26.
[3]Fox JC, Patel VV. Apoptosis and thecardiovascular system. ACC Curr J Rev1998;March/April: 13-5.
[4]Borutaite V, Brown GC. Mitochondria inapoptosis of ischemic heart.FEBS Lett2003;541: 1-5.
[5]Suleiman MS, Halestrap AP, Griffiths EJ.Mitochondria: Atarget for myocardial protection.Pharmacol Ther2001; 89: 29-46.
[6]Stewart CEH, Lin H, Holly JMP, Suleiman MS.Insulin-like growth factors, apoptosis andmyocardial protection during ischemia andreperfusion.J Endocrinol1998; 159: 27.
[7]Trueblood NA, Ramasamy R, Wang LF, SchaeferS. Niacin protects the isolated heart fromischemia-reperfusion injury. Am J Physiol Heart-Circ Physiol2000; 279: H764-71.
[8]Hausenloy DJ, Duchen MR, Yellon DM.Inhibiting mitochondrial permeability transitionpore opening at reperfusion protects againstischemia-reperfusion injury. Cardiovasc Res2003;60: 617-25.
[9]Tosaki A, Engelman DT, Engelman RM, DasDK. The evolution of diabetic response toischemia/reperfusion and preconditioning inisolated working rat hearts. Cardiovasc Res 1996;31: 526-36.
[10]Piot CA, Padmanaban D, Ursell PC, Sievers RE,Wolfe CL. Ischemic preconditioning decreasesapoptosis in rat hearts in vivo. Circulation1997;96: 1598-604.
[11]Scarabelli TM, Knight RA, Rayment NB, CooperTJ, Stephanou A, Brar BK, Lawrence KM, SantilliG, Latchman DS, Baxter GF, Yellon DM.Quantitative assessment of cardiac myocyteapoptosis in tissue sections using the fluorescence-based tunel technique enhanced withcounterstains. J Immunol Methods1999; 228:23-8.
[12]Van Heerde WL, Robert-Offerman S, DumontE, Hofstra L, Doevendans PA, Smits JF, DaemenMJ, Reutelingsperger CP. Markers of apoptosis incardiovascular tissues: Focus on Annexin V.Cardiovasc Res 2000; 45: 549-59.
[13]Kumar D, Jugdutt BI. Apoptosis and oxidants inthe heart. J Lab Clin Med2003; 142: 288-97.
[14]Cui J, Das DK, Bertelli A, Tosaki A. Effects of L-carnitine and its derivatives on post-ischemiccardiac function, ventricular fibrillation andnecrotic and apoptotic cardiomyocyte death inisolated rat hearts. Mol Cell Biochem2003; 254:227-34.
[15]Najafi M, Garjani A. Study the effect of L-carnitine on infarct size in the ischemic-reperfusedisolated rat hearts. Pharm Sci J2005; 1: 47-52.
[16]Matera M, Bellinghieri G, Costantino G, SantoroD, Calvani M, Savica V. History of L-carnitine:Implications for renal disease. J Ren Nutr 2003;13: 2-14.
[17]Furuno T, Kanno T, Arita K, Asami M, Utsumi T,Doi Y, Inoue M, Utsumi K. Roles of long chainfatty acids and carnitine in mitochondrialmembrane permeability transition. BiochemPharmacol2001; 62: 1037-46.[18]Ishii T, Shimpo Y, Matsuoka Y, Kinoshita K.Anti-apoptotic effect of acetyl-L-carnitine andL-carnitine in primary cultured neurons. Jpn JPharmacol2000; 83: 119-24.
[19]Andrieu-Abadie N, Jaffrezou JP, Hatem S, LaurentG, Levade T, Mercadier JJ. L-carnitine preventsdoxorubicin-induced apoptosis of cardiacmyocytes: Role of inhibition of ceramidegeneration. FASEB J1999; 13: 1501-10.
[20]Mutomba MC, Yuan H, Konyavko M, Adachi S,Yokoyama CB, Esser V, McGarry JD, BabiorBM, Gottlieb RA. Regulation of the activity ofcaspases by L-carnitine and palmitoylcarnitine,FEBS Lett2000; 478: 19-25.[21]Vescovo G, Ravara B, Gobbo V, Sandri M,Angelini A, Della Barbera M, Dona M, Peluso G,Calvani M, Mosconi L, Dalla Libera L. L-carnitine: Apotential treatment for blockingapoptosis and preventing skeletal musclemyopathy in heart failure. Am J Physiol-Cellphysiol 2002; 283: C802-10
- Abstract Viewed: 273 times
- IJPS_Volume 3_Issue 1_Pages 19-24 Downloaded: 168 times