Effects of alpha-lipoic acid on skeletal muscle ischemia-reperfusion injury in mice



Alpha-lipoic acid, Ischemia-reperfusion injury, Skeletal muscle


Aim: The main problem in the treatment of cardiovascular diseases, which is the most common cause of death in the world today, is reperfusion injury. In our study, we investigated the effects of alpha-lipoic acid on lower limb ischemia-reperfusion injury.
Methods: In this study, 30 male Swiss breed albino mice weighing 45-65 g were used. Mice were randomly divided into 5 groups (Control group (C), Dimethyl Sulfoxide (DMSO) group, ischemia-reperfusion (IR) group, alpha-lipoic acid control group (ALA), alpha-lipoic acid - IR group (ALA+IR)), 6 mice in each group. All groups were administered 100 IU/kg intravenous heparin bolus 30 minutes before the procedure. Lower limb ischemia (2 hours) and reperfusion (2 hours) protocols were applied to the IR and ALA+IR groups by clamping the main femoral artery. Alpha-lipoic acid was administered to ALA and ALA+IR groups 1 hour before the experimental procedure (100 mg/kg intraperitoneal). After the experiment protocol, the lower limb gastrocnemius muscles were collected from the sacrificed mice and total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), Myeloperoxidase (MPO) and Malondialdehyde (MDA) levels were determined in the tissue. In addition, edema, necrosis, and inflammatory cell infiltration levels in the skeletal muscle were determined by histologic grading, and apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method.
Results: TAS measurements of ALA group subjects were higher than the control group (P=0.01). The TOS level of the ALA+IR group was lower than the IR group (P=0.01), but higher than the C, ALA, and DMSO groups. The OSI index of the IR group was significantly higher than the ALA+IR group (P=0.01). It was observed that the IR group was at higher levels than the ALA+IR group (P=0.01). MDA measurements of IR group subjects were higher than that of the C, ALA, DMSO, ALA+IR groups (P=0.01). Edema of the IR and ALA+IR group subjects were higher than the C, ALA, DMSO groups (P=0.01). Necrosis measurements of IR and ALA+IR group subjects were higher than C, ALA, DMSO groups (P=0.01). Inflammatory cell infiltration measurements of IR and ALA+IR group subjects were higher than C, ALA, DMSO groups (P=0.01). Apoptosis level was significantly lower in the ALA+IR group than in the IR group. (P=0.01).
Conclusion: The results showed us that alpha-lipoic acid has a protective effect against oxidative damage, inflammation, and apoptosis in the tissue in lower limb ischemia-reperfusion. 


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Carter SE, Faulkner A, Rakobowchuk M. The role of prostaglandin and antioxidant availability in recovery from forearm ischemia-reperfusion injury in humans. J Hypertens. 2014 Feb;32(2):339-51. doi: 10.1097/HJH.0000000000000033. PMID: 24296519; PMCID: PMC3914903.

Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol. 2000 Feb;190(3):255-66. doi: 10.1002/(SICI)1096-9896(200002)190:3<255::AID-PATH526>3.0.CO;2-6. PMID: 10685060.

Geldi O, Kubat E, Ünal CS, Canbaz S. Acetaminophen Mitigates Myocardial Injury Induced by Lower Extremity Ischemia-Reperfusion in Rat Model. Braz J Cardiovasc Surg. 2018 May-Jun;33(3):258-64. doi: 10.21470/1678-9741-2017-0218. PMID: 30043918; PMCID: PMC6089134.

Eken H, Kurnaz E. Biochemical and histopathological evaluation of taxifolin: An experimental study in a rat model of liver ischemia reperfusion injury. J Surg Med. 2019;3(7):494-7.

Biewenga GP, Haenen GR, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol. 1997 Sep;29(3):315-31. doi: 10.1016/s0306-3623(96)00474-0. PMID: 9378235.

Cakatay U. Pro-oxidant actions of alpha-lipoic acid and dihydrolipoic acid. Med Hypotheses. 2006;66(1):110-7. doi: 10.1016/j.mehy.2005.07.020. Epub 2005 Sep 13. PMID: 16165311.

St Clair D, Zhao Y, Chaiswing L, Oberley T. Modulation of skin tumorigenesis by SOD. Biomed Pharmacother. 2005 May;59(4):209-14. doi: 10.1016/j.biopha.2005.03.004. Epub 2005 Mar 17. PMID: 15862717.

Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM. Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem. 2004 May;11(9):1135-46. doi: 10.2174/0929867043365387. PMID: 15134511.

Kılıç Y, Özer A, Tatar T, Zor MH, Kirişçi M, Kartal H, et al. Effect of picroside II on hind limb ischemia reperfusion injury in rats. Drug Des Devel Ther. 2017 Jun 26;11:1917-25. doi: 10.2147/DDDT.S132401. PMID: 28721011; PMCID: PMC5500556.

Yumru M, Savas HA, Kalenderoglu A, Bulut M, Celik H, Erel O. Oxidative imbalance in bipolar disorder subtypes: a comparative study.

Prog Neuropsychopharmacol Biol Psychiatry. 2009 Aug 31;33(6):1070-4. doi: 10.1016/j.pnpbp.2009.06.005. Epub 2009 Jun 12. PMID: 19527764.

Kosecik M, Erel O, Sevinc E, Selek S. Increased oxidative stress in children exposed to passive smoking. Int J Cardiol. 2005 Apr 8;100(1):61-4. doi: 10.1016/j.ijcard.2004.05.069. PMID: 15820286.

Harma M, Harma M, Erel O. Increased oxidative stress in patients with hydatidiform mole. Swiss Med Wkly. 2003 Nov 1;133(41-42):563-6. PMID: 14691728.

Tullis MJ, Brown S, Gewertz BL. Hepatic influence on pulmonary neutrophil sequestration following intestinal ischemia-reperfusion. J Surg Res. 1996 Dec;66(2):143-6. doi: 10.1006/jsre.1996.0386. PMID: 9024826.

Witt EH, Reznick AZ, Viguie CA, Starke-Reed P, Packer L. Exercise, oxidative damage and effects of antioxidant manipulation. J Nutr. 1992 Mar;122(3 Suppl):766-73. doi: 10.1093/jn/122.suppl_3.766. PMID: 1514950.

Tural K, Ozden O, Bilgi Z, Kubat E, Ermutlu CS, Merhan O, et al. The protective effect of betanin and copper on heart and lung in end organ ischemia reperfusion injury. Bratisl Lek Listy. 2020;121(3):211-7. doi: 10.4149/BLL_2020_032. PMID: 32115979.

Elmali N, Esenkaya I, Karadağ N, Taş F, Elmali N. Effects of resveratrol on skeletal muscle in ischemia-reperfusion injury. Ulus Travma Acil Cerrahi Derg. 2007 Oct;13(4):274-80. PMID: 17978908.

Erkanli K, Kayalar N, Erkanli G, Ercan F, Sener G, Kirali K. Melatonin protects against ischemia/reperfusion injury in skeletal muscle. J Pineal Res. 2005 Oct;39(3):238-42. doi: 10.1111/j.1600-079X.2005.00240.x. PMID: 16150103.

Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM. Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem. 2004 May;11(9):1135-46. doi: 10.2174/0929867043365387. PMID: 15134511.

Packer L, Witt EH, Tritschler HJ. alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med. 1995 Aug;19(2):227-50. doi: 10.1016/0891-5849(95)00017-r. PMID: 7649494.

Lu S, Wang X, Wen L, Han Z, Tao T, Guan D. [Effect of superoxide dismutase on adhesion molecules expression in skeletal muscle ischemia/reperfusion injury in rats]. Zhonghua Yi Xue Za Zhi. 2002 Jun 25;82(12):840-3. Chinese. PMID: 12126535.

Alaçam B, Ek RO, Yıldız Y, Serter M, Boylu NT, Temoçin S. Abdominalaorta iskemi-reperfüzyonuna bağlı gelişen akciğer hasarında karnozinin etkisi ADÜ Tıp Fakültesi Dergisi. 2010;11(3):41-7.

Govind J. Lumbar radicular pain. Aust Fam Physician. 2004 Jun;33(6):409-12. PMID: 15253601.

Deng C, Sun Z, Tong G, Yi W, Ma L, Zhao B, et al. α-Lipoic acid reduces infarct size and preserves cardiac function in rat myocardial ischemia/reperfusion injury through activation of PI3K/Akt/Nrf2 pathway. PLoS One. 2013;8(3):e58371. doi: 10.1371/journal.pone.0058371. Epub 2013 Mar 7. PMID: 23505496; PMCID: PMC3591314.

Mendoza-Núñez VM, García-Martínez BI, Rosado-Pérez J, Santiago-Osorio E, Pedraza-Chaverri J, Hernández-Abad VJ. The Effect of 600 mg Alpha-lipoic Acid Supplementation on Oxidative Stress, Inflammation, and RAGE in Older Adults with Type 2 Diabetes Mellitus. Oxid Med Cell Longev. 2019 Jun 12;2019:3276958. doi: 10.1155/2019/3276958. PMID: 31285784; PMCID: PMC6594273.

Petersen Shay K, Moreau RF, Smith EJ, Hagen TM. Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity. IUBMB Life. 2008 Jun;60(6):362-7. doi: 10.1002/iub.40. PMID: 18409172.

Yan W, Li N, Hu X, Huang Y, Zhang W, Wang Q, et al. Effect of oral ALA supplementation on oxidative stress and insulin sensitivity among overweight/obese adults: a double-blinded, randomized, controlled, cross-over intervention trial. Int J Cardiol. 2013 Jul 31;167(2):602-3. doi: 10.1016/j.ijcard.2012.09.232. Epub 2012 Oct 25. PMID: 23102606

He L, Liu B, Dai Z, Zhang HF, Zhang YS, Luo XJ, et al. Alpha lipoic acid protects heart against myocardial ischemia-reperfusion injury through a mechanism involving aldehyde dehydrogenase 2 activation. Eur J Pharmacol. 2012 Mar 5;678(1-3):32-8. doi: 10.1016/j.ejphar.2011.12.042. Epub 2012 Jan 12. PMID: 22266491.






Research Article

How to Cite

Kartal H, Büyük B. Effects of alpha-lipoic acid on skeletal muscle ischemia-reperfusion injury in mice. J Surg Med [Internet]. 2020 Jul. 1 [cited 2024 May 20];4(7):567-72. Available from: https://jsurgmed.com/article/view/764953