The Effect Of L-Carnitine And Alpha Lipoic Acid Administration With Exercise In Old Rats On Energy Metabolism Related To Oxidative Stress Parameters

Year 2024, , 476 - 483, 28.06.2024

Kardelen Kocaman Kalkan , Neslihan Şirin , Atakan Tepe , Ali Gök , Tolga Altaş , Kağan Ağan , Pınar Yıldız Gülhan , Merve Alpay

https://doi.org/10.33808/clinexphealthsci.1369239

Abstract

Objective: This study aims to contribute novel insights by investigating the potential positive effects of a combined dietary supplement and exercise program on mitochondrial oxidative stress and energy metabolism in aging. Focusing on the protective impact of Alpha Lipoic Acid (ALA), a potent antioxidant, against exercise-induced mitochondrial oxidative stress in rats, we also assess how L-Carnitine administration affects exercise ability by analyzing resistin and HbA1c levels, indicators linked to insulin resistance and cellular sensitivity.
Methods: In this 10-day study, 42 old male Sprague Dawley rats (weighing 400±10 g, aged 15–17 weeks) were divided into six groups (n=7): Control, Exercise, L-Carnitine, Alpha Lipoic Acid (ALA), L-Carnitine+Exercise, ALA+Exercise. Relevant groups received daily oral gavage doses of L- Carnitine (50 mg/ml) and ALA (18 mg/ml). Exercise groups underwent treadmill sessions. On day 10, blood samples were quantitatively analyzed for HbA1c and Resistin levels using a Cusabio ELISA assay kit (China).
Results: ALA supplementation synergistically reduced resistin and HbA1c levels, individually and combined with exercise. Conversely, L-Carnitine supplement, alone or with exercise, increased resistin levels but it caused a decrease in HbA1c levels.
Conclusions: The data indicated a minor, insignificant decrease in resistin levels for the exercise and ALA groups, with a statistically significant difference in HbA1c levels among all groups. Exercise alone positively impacted both HbA1c and resistin levels, suggesting a potential counteraction of age-related oxidative stress and a positive influence on energy metabolism through an appropriate diet and exercise program. Further studies are required to explore specific metabolic pathways and relationships identified in our findings.

Keywords

Aging, exercise, resistin, HbA1c, oxidative stress

Thanks

We would like to thank Doç. Dr. Mehmet Ali SUNGUR for his contribution to our statistical analysis.

References

• Jadeja RN, Martin PM, Chen W. Mitochondrial oxidative stress and energy metabolism: impact on aging and longevity. Oxid Med Cell Longev. 2021;2021(4):9789086. DOI:10.1155/2021/9789086.
• Srivastava S. The mitochondrial basis of aging and age-related disorders. Genes (Basel). 2017;8(12):398. DOI:10.3390/genes8120398.
• Bolduc JA, Collins JA, Loeser RF. Reactive oxygen species, aging and articular cartilage homeostasis. Free Radic Biol Med. 2019;132:73-82. DOI:10.1016/j.freeradbiomed.2018.08.038.
• Wu NN, Zhang Y, Ren J. Mitophagy, mitochondrial dynamics and homeostasis in cardiovascular aging. Oxid Med Cell Longev. 2019;2019(4):9825061. DOI:10.1155/2019/9825061.
• Andreadi A, Bellia A, Di Daniele N, Meloni M, Lauro R, Della-Morte D, Lauro D. The molecular link between oxidative stress, insulin resistance, and type 2 diabetes:A target for new therapies against cardiovascular diseases. Curr Opin Pharmacol. 2022;62:85-96. DOI:10.1016/j.coph.2021.11.010.
• Newsholme P, Cruzat VF, Keane KN, Carlessi R, de Bittencourt PI Jr. Molecular mechanisms of ROS production and oxidative stress in diabetes. Biochem J. 2016;473(24):4527-4550. DOI:10.1042/BCJ20160503C.
• Newsholme P, Keane KN, Carlessi R, Cruzat V. Oxidative stress pathways in pancreatic β-cells and insulin-sensitive cells and tissues: Importance to cell metabolism, function, and dysfunction. Am J Physiol Cell Physiol. 2019;317(3):C420-C433. DOI:10.1152/ajpcell.00141.2019
• Pinti MV, Fink GK, Hathaway QA, Durr AJ, Kunovac A, Hollander JM. Mitochondrial dysfunction in type 2 diabetes mellitus: An organ-based analysis. Am J Physiol Endocrinol Metab. 2019;316(2):E268-E285. DOI:10.1152/ajpendo.00314.2018.
• Sallam N, Laher I. Exercise modulates oxidative stress and inflammation in aging and cardiovascular diseases. Oxid Med Cell Longev. 2016;2016:7239639. DOI:10.1155/2016/7239639.
• Carapeto PV, Aguayo-Mazzucato C. Effects of exercise on cellular and tissue aging. Aging (Albany NY). 2021;13(10):14522-14543. DOI:10.18632/aging.203051.
• Colleluori G, Villareal DT. Aging, obesity, sarcopenia and the effect of diet and exercise intervention. Exp Gerontol. 2021;155:111561. DOI:10.1016/j.exger.2021.111561.
• Pekala J, Patkowska-Sokoła B, Bodkowski R, Jamroz D, Nowakowski P, Lochyński S, Librowski T. L-carnitine--metabolic functions and meaning in humans life. Curr Drug Metab. 2011;12(7):667- 78. DOI:10.2174/138920011796504536.
• Adeva-Andany MM, Calvo-Castro I, Fernández-Fernández C, Donapetry-García C, Pedre-Piñeiro AM. Significance of l-carnitine for human health. IUBMB Life. 2017;69(8):578-594. DOI:10.1002/iub.1646.
• Nicassio L, Fracasso F, Sirago G, Musicco C, Picca A, Marzetti E, Calvani R, Cantatore P, Gadaleta MN, Pesce V. Dietary supplementation with acetyl-l-carnitine counteracts age-related alterations of mitochondrial biogenesis, dynamics and antioxidant defenses in brain of old rats. Exp Gerontol. 2017;98:99-109. DOI:10.1016/j.exger.2017.08.017.
• Fielding R, Riede L, Lugo JP, Bellamine A. L-carnitine supplementation in recovery after exercise. Nutrients. 2018;10(3):349. DOI:10.3390/nu10030349.
• Mansour HH. Protective role of carnitine ester against radiation-induced oxidative stress in rats. Pharmacol Res. 2006;54(3):165-71. DOI:10.1016/j.phrs.2006.04.003.
• Kraemer WJ, Volek JS, Dunn-Lewis C. L-carnitine supplementation: Influence upon physiological function. Curr Sports Med Rep. 2008;7(4):218-23. DOI:10.1249/JSR.0b013e318180735c.
• Cha YS. Effects of l-carnitine on obesity, diabetes, and as an ergogenic aid. Asia Pac J Clin Nutr. 2008;17:306-8. PMID: 18296364.
• Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009;1790(10):1149-60. DOI:10.1016/j.bbagen.2009.07.026.
• Tripathi AK, Ray AK, Mishra SK, Bishen SM, Mishra H, Khurana A. Molecular and therapeutic insights of alpha-lipoic acid as a potential molecule for disease prevention. Rev Bras Farmacogn. 2023;33(2):272-287. DOI:10.1007/s43450-023-00370-1.
• Rochette L, Ghibu S, Muresan A, Vergely C. Alpha-lipoic acid: Molecular mechanisms and therapeutic potential in diabetes. Can J Physiol Pharmacol. 2015;93(12):1021-7. DOI:10.1139/cjpp-2014-0353.
• Salehi B, Berkay Yılmaz Y, Antika G, Boyunegmez Tumer T, Fawzi Mahomoodally M, Lobine D, Akram M, Riaz M, Capanoglu E, Sharopov F, Martins N, Cho WC, Sharifi-Rad J. Insights on the use of α-lipoic acid for therapeutic purposes. Biomolecules. 2019;9(8):356. DOI:10.3390/biom9080356.
• Skibska B, Goraca A. The protective effect of lipoic acid on selected cardiovascular diseases caused by age-related oxidative stress. Oxid Med Cell Longev. 2015;2015:313021. DOI:10.1155/2015/313021.
• Akbari M, Ostadmohammadi V, Lankarani KB, Tabrizi R, Kolahdooz F, Khatibi SR, Asemi Z. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Metabolism. 2018;87:56-69. DOI:10.1016/j.metabol.2018.07.002.
• Capece U, Moffa S, Improta I, Di Giuseppe G, Nista EC, Cefalo CMA, Cinti F, Pontecorvi A, Gasbarrini A, Giaccari A, Mezza T. Alpha-lipoic acid and glucose metabolism: A comprehensive update on biochemical and therapeutic features. Nutrients. 2022;15(1):18. DOI:10.3390/nu15010018.
• Acquarone E, Monacelli F, Borghi R, Nencioni A, Odetti P. Resistin: A reappraisal. Mech Ageing Dev. 2019;178:46-63. DOI:10.1016/j.mad.2019.01.004.
• Huang X, Yang Z. Resistin's, obesity and insulin resistance: the continuing disconnect between rodents and humans. J Endocrinol Invest. 2016;39(6):607-15. DOI:10.1007/s40618-015-0408-2
• Soygüden A, Cerit E. Yaşlılar için egzersiz uygulamalarının önemi. Hitit Üniversitesi Sosyal Bilimler Enstitüsü Dergisi. 2015;8(1):197-224. DOI:10.17218/husbed.58321 (Turkish).
• Pekala J, Patkowska-Sokoła B, Bodkowski R, Jamroz D, Nowakowski P, Lochyński S, Librowski T. L-carnitine metabolic functions and meaning in humans life. Curr Drug Metab. 2011;12(7):667-78. DOI:10.2174/138920011796504536.
• Kalaiselvi T, Panneerselvam C. Effect of l-carnitine on the status of lipid peroxidation and antioxidants in aging rats. The Journal of Nutritional Biochemistry. 1998;9(10):575-581. DOI:10.1016/S0955-2863(98)00052-7.
• Radin MS. Pitfalls in hemoglobin A1c measurement: when results may be misleading. J Gen Intern Med. 2014;29(2):388-94. DOI:10.1007/s11606-013-2595-x.
• Kurt İ. Glikozile hemoglobin (HbA1c) ölçümü ve diabetes mellitusun uzun dönem glisemik kontrolünde kullanılması. Gülhane Tıp Dergisi. 2003:387-395. (Turkish)
• Colberg SR, Sigal RJ, Yardley JE, Riddell MC, Dunstan DW, Dempsey PC, Horton ES, Castorino K, Tate DF. Physical activity/exercise and diabetes: A position statement of the american diabetes association. Diabetes Care. 2016;39(11):2065-2079. DOI:10.2337/dc16-1728.
• Umpierre D, Ribeiro PA, Kramer CK, Leitão CB, Zucatti AT, Azevedo MJ, Gross JL, Ribeiro JP, Schaan BD. Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: A systematic review and meta-analysis. JAMA. 2011;305(17):1790-9. DOI:10.1001/jama.2011.576.
• Tripathi AK, Ray AK, Mishra SK, Bishen SM, Mishra H, Khurana A. Molecular and therapeutic insights of alpha-lipoic acid as a potential molecule for disease prevention. Rev Bras Farmacogn. 2023;33(2):272-287. DOI:10.1007/s43450-023-00370-1.
• Ergene E. Alfa lipoik asit ve metabolik etkileri üzerine bir araştırma. Adnan Menderes Üniversitesi Sağlık Bilimleri Fakültesi Dergisi. 2018;2(3):159-165 (Turkish).
• Öğüt S, Atay E. Yaşlılık ve oksidatif stres. SDÜ Tıp Fakültesi Dergisi. 2012;19(2): 68-74 (Turkish).
• Birinci MC, Karadeniz A. Yüzme egzersizi yaptırılan farelere alfa-lipoik asit uygulamasının lipid peroksidasyon, kreatin kinaz ve laktat düzeyleri üzerine etkisinin incelenmesi. KSÜ Tıp Fak Der. 2023;18(1):102-107. DOI:10.17517/ksutfd.1080134 (Turkish)
• Kayali R, Cakatay U, Akçay T, Altuğ T. Effect of alpha-lipoic acid supplementation on markers of protein oxidation in post-mitotic tissues of ageing rat. Cell Biochem Funct. 2006;24(1):79-85. DOI:10.1002/cbf.1190.