Abstract
The aim of this study is to investigate the effects of limonene, alone or associated with therapeutic ultrasound, on oxidative stress following skeletal muscle injury. Thirty male Wistar rats were divided into 5 groups: CTR-control, MI-muscle injury without treatment, TPU-therapeutic pulsed ultrasound alone, TPU + LIM-phonophoresis with 5% limonene, and LIM-5% limonene applied topically. Muscle injury was induced by a mechanical abrupt impact over gastrocnemius muscle. The animals were treated in the following intervals: 2, 12, 24, 48, 72, and 96 h after injury. Blood and gastrocnemius samples were collected 98 h after lesion for data analysis. Creatine kinase (CK) and lactate dehydrogenase (LDH) activity, lipid peroxidation (TBARS) levels, catalase (CAT), and superoxide dismutase (SOD) activity were assessed. CK (p = 0.01), SOD activity (p < 0.01), and TBARS levels (p < 0.01) were increased after injury. There was no effect on LDH levels in any group. Phonophoresis (TABRS p < 0.01; SOD p = 0.01), TPU alone (TBARS p < 0.01; SOD p = 0.01), and LIM alone (TBARS p < 0.01; SOD p < 0.01) reduced TBARS levels and SOD activity after muscle injury. There was no change for CAT activity after injury. Only phonophoresis reduced CK activity after injury (p < 0.01). There was no difference between phonophoresis, TPU alone and LIM alone groups for TBARS, SOD, CAT, and LDH. Limonene alone and TPU alone were effective in reducing oxidative stress parameters after skeletal muscle injury. Only phonophoresis decreased CK activity. Skeletal muscle injury increases reactive oxidative species (ROS) levels and muscle proteins activity as creatine kinase (CK) and lactate dehydrogenase (LDH). Five percent limonene, alone or associated with therapeutic pulsed ultrasound, exhibited reduction of CK, superoxide dismutase (SOD) and catalase (CAT) activity, and lipid peroxidation markers (TBARS).
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Abbreviations
- ADP:
-
Adenosine diphosphate
- ATP:
-
Adenosine triphosphate
- CTR:
-
Control
- MI:
-
Muscle injury
- BHT:
-
Butylated hydroxytoluene
- CAT:
-
Catalase
- CK:
-
Creatine kinase
- ERA:
-
Effective radiation area
- GP6:
-
Glucose-6-phosphate
- LDH:
-
Lactate dehydrogenase
- MDA:
-
Malondialdehyde
- MHz:
-
Megahertz
- NADPH:
-
Nicotinamide adenine dinucleotide phosphate hydrogen
- NADP:
-
Nicotinamide adenine dinucleotide phosphate
- ROS:
-
Reactive oxygen substances
- SOD:
-
Superoxide dismutase
- TBARS:
-
Thiobarbituric acid reactive substances
- TPU:
-
Therapeutic pulsed ultrasound
References
Alfredo PP, Anaruma CA, Pião AC, João SM, Casarotto RA (2009) Effects of phonophoresis with Arnica montana onto acute inflammatory process in rat skeletal muscles: an experimental study. Ultrasonics. 49(4–5):466–471. https://doi.org/10.1016/j.ultras.2008.12.002
Araújo-Filho HG, Pereira EWM, Rezende MM, Menezes PP, Araújo AAS, Barreto RSS, Martins AOBPB, Albuquerque TR, Silva BAF, Alcantara IS, Coutinho HDM, Menezes IRA, Quintans-Junior LJ, Quintans JSS (2017) D-limonene exhibits superior antihyperalgesic effects in a β-cyclodextrin-complexed form in chronic musculoskeletal pain reducing Fos protein expression on spinal cord in mice. Neuroscience. 358:158–169. https://doi.org/10.1016/j.neuroscience.2017.06.037
Ben Hsouna A, Ben Halima N, Smaoui S, Hamdi N (2017) Citrus lemon essential oil: chemical composition, antioxidant and antimicrobial activities with its preservative effect against Listeria monocytogenes inoculated in minced beef meat. Lipids Health Dis 16(1):146. https://doi.org/10.1186/s12944-017-0487-5
Carvalho SS, Barja PR (2012) Photoacoustic analysis of the penetration kinetics of Cordia verbenacea DC in human skin. Int J Thermophys 33(10–11):1822–1826. https://doi.org/10.1007/s10765-012-1230-0
Case AJ. On the origin of superoxide dismutase: an evolutionary perspective of superoxide-mediated redox signaling. Antioxidants (Basel). 2017;6(4):82. Published 2017 Oct 30. doi:https://doi.org/10.3390/antiox6040082
Durço AO, de Souza DS, Heimfarth L, Miguel-Dos-Santos R, Rabelo TK, Oliveira Barreto T, Rhana P, Santos Santana MN, Braga WF, Santos Cruz JD, Lauton-Santos S, Santana-Filho VJ, Barreto RSS, Guimarães AG, Alvarez-Leite JI, Quintans Júnior LJ, Vasconcelos CML, Santos MRVD, Barreto AS (2019 Nov 22) D-limonene ameliorates myocardial infarction injury by reducing reactive oxygen species and cell apoptosis in a murine model. J Nat Prod 82(11):3010–3019. https://doi.org/10.1021/acs.jnatprod.9b00523
Ito F, Sono Y, Ito T. Measurement and clinical significance of lipid peroxidation as a biomarker of oxidative stress: oxidative stress in diabetes, atherosclerosis, and chronic inflammation. Antioxidants (Basel). 2019;8(3):72. Published 2019 Mar 25. doi:https://doi.org/10.3390/antiox8030072
Jitviriyanon S, Phanthong P, Lomarat P, Bunyapraphatsara N, Porntrakulpipat S, Paraksa N (2016) In vitro study of anti-coccidial activity of essential oils from indigenous plants against Eimeria tenella. Vet Parasitol 228:96–102. https://doi.org/10.1016/j.vetpar.2016.08.020
Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG (2010) NC3Rs reporting guidelines working group. Animal research: reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol 160(7):1577–1579. https://doi.org/10.1111/j.1476-5381.2010.00872.x
Kozakowska M, Pietraszek-Gremplewicz K, Jozkowicz A, Dulak J (2015) The role of oxidative stress in skeletal muscle injury and regeneration: focus on antioxidant enzymes. J Muscle Res Cell Motil 36(6):377–393. https://doi.org/10.1007/s10974-015-9438-9
Laumonier T, Menetrey J (2016) Muscle injuries and strategies for improving their repair. Journal of experimental orthopaedics 3(1):15. https://doi.org/10.1186/s40634-016-0051-7
Leal SS, Uchôa VT, Figuerêdo-Silva J, Soares RB, Mota DM, de Alencar RC, Maia Filho ALM, Sant'Ana AEG, Beltrame JM (2016) Phonophoresis effectiveness with Ximenia americana l. in rats tendon inflammation [article in Portuguese]. Rev Bras Med Esporte 22(5):355–360. https://doi.org/10.1590/1517-869220162205156899
Liu M, Wallin R, Wallmon A, Saldeen T (2002 May) Mixed tocopherols have a stronger inhibitory effect on lipid peroxidation than alpha-tocopherol alone. J Cardiovasc Pharmacol 39(5):714–721
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951 Nov) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275
McCord JM (2008) Superoxide dismutase, lipid peroxidation, and bell-shaped dose response curves. Dose Response 6(3):223–238. https://doi.org/10.2203/dose-response.08-012.McCord
Miller JA, Thompson PA, Hakim IA et al (2012) Safety and feasibility of topical application of limonene as a massage oil to the breast. J Cancer Ther 3(5A). https://doi.org/10.4236/jct.2012.325094
National Center for Biotechnology Information. PubChem Database. Limonene, CID=22311, https://pubchem.ncbi.nlm.nih.gov/compound/Limonene (accessed on May 01, 2020)
National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 2011. 8th edition. Washington (DC): National Academies Press (US)
Padhan D, Pattnaik S, Behera AK (2017) Growth-arresting activity of Acmella essential oil and its isolated component D-limonene (1, 8 P-Mentha Diene) against Trichophyton rubrum (microbial type culture collection 296). Pharmacogn Mag 13(Suppl 3):S555–S560. https://doi.org/10.4103/pm.pm_65_17
Rehman MU, Tahir M, Khan AQ, Khan R, Oday-O-Hamiza Lateef A, Hassan SK, Rashid S, Ali N, Zeeshan M, Sultana S (2014) D-limonene suppresses doxorubicin-induced oxidative stress and inflammation via repression of COX-2, iNOS, and NFκB in kidneys of Wistar rats. Exp Biol Med (Maywood) 239(4):465–476. https://doi.org/10.1177/1535370213520112
Rizzi CF, Mauriz JL, Freitas Corrêa DS, Moreira AJ, Zettler CG, Filippin LI, Marroni NP, González-Gallego J (2006) Effects of low-level laser therapy (LLLT) on the nuclear factor (NF)-kappaB signaling pathway in traumatized muscle. Lasers Surg Med 38(7):704–713
Saliba S, Mistry DJ, Perrin DH, Gieck J, Weltman A (2007) Phonophoresis and the absorption of dexamethasone in the presence of an occlusive dressing. J Athl Train 42(3):349–354
Sies H, Cadenas E (1985) Oxidative stress: damage to intact cells and organs. Philos Trans R Soc Lond Ser B Biol Sci 311(1152):617–631. https://doi.org/10.1098/rstb.1985.0168
Silveira PC, Victor EG, Schefer D, Silva LA, Streck EL, Paula MM, Pinho RA (2010 Jan) Effects of therapeutic pulsed ultrasound and dimethylsulfoxide (DMSO) phonophoresis on parameters of oxidative stress in traumatized muscle. Ultrasound Med Biol 36(1):44–50. https://doi.org/10.1016/j.ultrasmedbio.2009.09.001
Soundharrajan I, Kim DH, Srisesharam S, Kuppusamy P, Sivanesan R, Choi KC (2018) Limonene promotes osteoblast differentiation and 2-deoxy-d-glucose uptake through p38MAPK and Akt signaling pathways in C2C12 skeletal muscle cells. Phytomedicine. 45:41–48. https://doi.org/10.1016/j.phymed.2018.03.019
Sousa Filho LF, Menezes PP, Santana DVS, Lima BS, Saravanan S, Almeida GKM, Filho JERM, Santos MMB, Araújo AAS, de Oliveira ED (2018) Effect of pulsed therapeutic ultrasound and Diosmin on skeletal muscle oxidative parameters. Ultrasound Med Biol 44(2):359–367. https://doi.org/10.1016/j.ultrasmedbio.2017.09.009
Victor EG, Silveira PC, Possato JC, da Rosa GL, Munari UB, de Souza CT, Pinho RA, da Silva L, Streck EL, Paula MM (2012) Pulsed ultrasound associated with gold nanoparticle gel reduces oxidative stress parameters and expression of pro-inflammatory molecules in an animal model of muscle injury. J Nanobiotechnology 10:11. https://doi.org/10.1186/1477-3155-10-11
Vieira AJ, Beserra FP, Souza MC, Totti BM, Rozza AL (2018) Limonene: aroma of innovation in health and disease. Chem Biol Interact 283:97–106. https://doi.org/10.1016/j.cbi.2018.02.007
Wojtunik KA, Ciesla LM, Waksmundzka-Hajnos M (2014 Sep 17) Model studies on the antioxidant activity of common terpenoid constituents of essential oils by means of the 2,2-diphenyl-1-picrylhydrazyl method. J Agric Food Chem 62(37):9088–9094. https://doi.org/10.1021/jf502857s
Wojtunik-Kulesza KA, Kasprzak K, Oniszczuk T, Oniszczuk A (2019 Dec) Natural Monoterpenes: much more than only a scent. Chem Biodivers 16(12):e1900434. https://doi.org/10.1002/cbdv.201900434
Yu X, Lin H, Wang Y, Lv W, Zhang S, Qian Y, Deng X, Feng N, Yu H, Qian B (2018) D-limonene exhibits antitumor activity by inducing autophagy and apoptosis in lung cancer. Onco Targets Ther 11:1833–1847. https://doi.org/10.2147/OTT.S155716
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MMBS: conceptualization; methodology; formal analysis; visualization; writing—original draft preparation. LFSF: formal analysis; writing—review and editing; visualization; project administration. JBS: validation; investigation; resources; project administration. JERMF: validation; investigation; resources; formal analysis. TRRM: validation; investigation; resources; formal analysis. MSS: validation; investigation; resources. CMLV: validation; investigation; resources. SLS: validation; investigation; resources. EDO: conceptualization; methodology; resources; supervision; project administration; writing—review and editing. The authors declare that all data were generated in-house and that no paper mill was used.
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Highlights
• Phonophoresis is not superior for reducing oxidative stress
• It is not clear the relation between drug absorption and therapeutic effect
• Five percent limonene alone reduces oxidative stress following muscle trauma
• Limonene may be a promising therapeutic agent for muscle injuries
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Santos, M.M.B., Filho, L.F.S., De Souza, J.B. et al. Topical application of (S)-(–)-limonene is as effective as phonophoresis for improving oxidative parameters of injured skeletal muscle in rats. Naunyn-Schmiedeberg's Arch Pharmacol 393, 2293–2300 (2020). https://doi.org/10.1007/s00210-020-01941-y
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DOI: https://doi.org/10.1007/s00210-020-01941-y