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Recent Advances in Inflammation & Allergy Drug Discovery

Author(s): Fatemeh Forouzanfar, Mohammad Moein Vakilzadeh, Ali Mehri, Ali Mohammad Pourbagher-Shahri, Shiva Ganjali, Mitra Abbasifard* and Amirhossein Sahebkar*

DOI: 10.2174/2772270817666230825093141

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Anti-arthritic and Antioxidant Effects of Trehalose in an Experimental Model of Arthritis

Page: [145 - 151] Pages: 7

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Abstract

Background: The purpose of the present study was to study the potential anti-arthritic and antioxidant effects of trehalose in an experimental model of complete Freund’s adjuvant (CFA)-induced arthritis.

Methods: Arthritis was induced via subcutaneous injection of CFA (0.1) into the right footpad of each rat. Trehalose (10 mg/kg per day) and indomethacin (5 mg/kg) as a reference drug were intraperitoneally injected into CFA-induced arthritic rats from days 0 to 21. Changes in paw volume, pain responses, arthritic score, and oxidative/antioxidative parameters were determined.

Results: Trehalose administration could significantly decrease arthritis scores (p <0.01) and paw edema (p <0.001), and significantly increase the nociceptive threshold (p <0.05) in CFA-induced arthritic rats. Trehalose also significantly reduced the pro-oxidant-antioxidant balance values when compared to CFA treatment alone. In addition, no significant difference was found between the trehalose group and indomethacin as a positive control group.

Conclusion: The current study suggests that trehalose has a protective effect against arthritis, which may be mediated by antioxidative effects of this disaccharide.

Graphical Abstract

[1]
Bala A, Mondal C, Haldar PK, Khandelwal B. Oxidative stress in inflammatory cells of patient with rheumatoid arthritis: Clinical efficacy of dietary antioxidants. Inflammopharmacology 2017; 25(6): 595-607.
[http://dx.doi.org/10.1007/s10787-017-0397-1] [PMID: 28929423]
[2]
Gibofsky A. Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis. Am J Manag Care 2012; 18(13) (Suppl.): S295-302.
[PMID: 23327517]
[3]
Khojah HM, Ahmed S, Abdel-Rahman MS, Hamza AB. Reactive oxygen and nitrogen species in patients with rheumatoid arthritis as potential biomarkers for disease activity and the role of antioxidants. Free Radic Biol Med 2016; 97: 285-91.
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.06.020] [PMID: 27344969]
[4]
Sun Y, Liu J, Xin L, et al. Xinfeng capsule inhibits inflammation and oxidative stress in rheumatoid arthritis by up-regulating LINC00638 and activating Nrf2/HO-1 pathway. J Ethnopharmacol 2023; 301: 115839.
[http://dx.doi.org/10.1016/j.jep.2022.115839] [PMID: 36272490]
[5]
Chen Q, Haddad GG. Role of trehalose phosphate synthase and trehalose during hypoxia: From flies to mammals. J Exp Biol 2004; 207(18): 3125-9.
[http://dx.doi.org/10.1242/jeb.01133] [PMID: 15299033]
[6]
Jain NK, Roy I. Effect of trehalose on protein structure. Protein Sci 2009; 18(1): 24-36.
[PMID: 19177348]
[7]
Lee HJ, Yoon YS, Lee SJ. Mechanism of neuroprotection by trehalose: Controversy surrounding autophagy induction. Cell Death Dis 2018; 9(7): 712.
[http://dx.doi.org/10.1038/s41419-018-0749-9] [PMID: 29907758]
[8]
Echigo R, Shimohata N, Karatsu K, et al. Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage. J Transl Med 2012; 10(1): 80.
[http://dx.doi.org/10.1186/1479-5876-10-80] [PMID: 22546323]
[9]
Forouzanfar F, Guest PC, Jamialahmadi T, Sahebkar A. Hepatoprotective effect of trehalose: Insight into its mechanisms of action. natural products and human diseases: Pharmacology. In: Molecular Targets, and Therapeutic Benefits 2021; pp. 489-500.
[10]
Hosseinpour-Moghaddam K, Caraglia M, Sahebkar A. Autophagy induction by trehalose: Molecular mechanisms and therapeutic impacts. J Cell Physiol 2018; 233(9): 6524-43.
[http://dx.doi.org/10.1002/jcp.26583] [PMID: 29663416]
[11]
Lee H, Ko EH, Lai M, et al. Delineating the relationships among the formation of reactive oxygen species, cell membrane instability and innate autoimmunity in intestinal reperfusion injury. Mol Immunol 2014; 58(2): 151-9.
[http://dx.doi.org/10.1016/j.molimm.2013.11.012] [PMID: 24365749]
[12]
Sahebkar A, Khalifeh M, Barreto GE. Therapeutic potential of trehalose in neurodegenerative diseases: The knowns and unknowns. Neural Regen Res 2021; 16(10): 2026-7.
[http://dx.doi.org/10.4103/1673-5374.308085] [PMID: 33642389]
[13]
Khalifeh M, Barreto GE, Sahebkar A. Trehalose as a promising therapeutic candidate for the treatment of Parkinson’s disease. Br J Pharmacol 2019; 176(9): 1173-89.
[http://dx.doi.org/10.1111/bph.14623] [PMID: 30767205]
[14]
Khalifeh M, Read MI, Barreto GE, Sahebkar A. Trehalose against Alzheimer’s Disease: Insights into a potential therapy. BioEssays 2020; 42(8): 1900195.
[http://dx.doi.org/10.1002/bies.201900195] [PMID: 32519387]
[15]
Du J, Liang Y, Xu F, Sun B, Wang Z. Trehalose rescues Alzheimer’s disease phenotypes in APP/PS1 transgenic mice. J Pharm Pharmacol 2013; 65(12): 1753-6.
[http://dx.doi.org/10.1111/jphp.12108] [PMID: 24236985]
[16]
Sarkar S, Chigurupati S, Raymick J, et al. Neuroprotective effect of the chemical chaperone, trehalose in a chronic MPTP-induced Parkinson’s disease mouse model. Neurotoxicology 2014; 44: 250-62.
[http://dx.doi.org/10.1016/j.neuro.2014.07.006] [PMID: 25064079]
[17]
Tanaka M, Machida Y, Niu S, et al. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat Med 2004; 10(2): 148-54.
[http://dx.doi.org/10.1038/nm985] [PMID: 14730359]
[18]
Shimohata N, Echigo R, Karatsu K, et al. Trehalose decreases blood clotting in the cerebral space after experimental subarachnoid hemorrhage. J Vet Med Sci 2020; 82(5): 566-70.
[http://dx.doi.org/10.1292/jvms.19-0201] [PMID: 32173691]
[19]
Billiau A, Matthys P. Modes of action of Freund’s adjuvants in experimental models of autoimmune diseases. J Leukoc Biol 2001; 70(6): 849-60.
[http://dx.doi.org/10.1189/jlb.70.6.849] [PMID: 11739546]
[20]
McNamee K, Williams R, Seed M. Animal models of rheumatoid arthritis: How informative are they? Eur J Pharmacol 2015; 759: 278-86.
[http://dx.doi.org/10.1016/j.ejphar.2015.03.047] [PMID: 25824900]
[21]
Kumar A, Dhaliwal N, Dhaliwal J, Dharavath RN, Chopra K. Astaxanthin attenuates oxidative stress and inflammatory responses in complete freund-adjuvant-induced arthritis in rats. Pharmacol Rep 2020; 72(1): 104-14.
[http://dx.doi.org/10.1007/s43440-019-00022-z] [PMID: 32016833]
[22]
Forouzanfar F, Pourbagher-Shahri AM, Ghazavi H. Evaluation of antiarthritic and antinociceptive effects of cedrol in a rat model of arthritis Oxid Med Cell Longev 2022; 2022.
[http://dx.doi.org/10.1155/2022/4943965]
[23]
Rakhshandeh H, Ghorbanzadeh A, Negah SS, Akaberi M, Rashidi R, Forouzanfar F. Pain-relieving effects of lawsonia inermis on neuropathic pain induced by chronic constriction injury. Metab Brain Dis 2021; 36(7): 1709-16.
[http://dx.doi.org/10.1007/s11011-021-00773-w] [PMID: 34169409]
[24]
Ganjali S, Keshavarz R, Hosseini S, et al. Evaluation of oxidative stress status in familial hypercholesterolemia. J Clin Med 2021; 10(24): 5867.
[http://dx.doi.org/10.3390/jcm10245867] [PMID: 34945165]
[25]
Ghayour-Mobarhan M, Alamdari DH, Moohebati M, et al. Determination of prooxidant--antioxidant balance after acute coronary syndrome using a rapid assay: A pilot study. Angiology 2009; 60(6): 657-62.
[http://dx.doi.org/10.1177/0003319709333868] [PMID: 19398426]
[26]
Quiñonez-Flores CM, González-Chávez SA, Del Rio Najera D, Pacheco-Tena C. Oxidative stress relevance in the pathogenesis of the rheumatoid arthritis: A systematic review. BioMed research international 2016; 2016.
[http://dx.doi.org/10.1155/2016/6097417]
[27]
Yu Y, Li S, Liu Y, et al. Fibroblast growth factor 21 (FGF21) ameliorates collagen-induced arthritis through modulating oxidative stress and suppressing nuclear factor-kappa B pathway. Int Immunopharmacol 2015; 25(1): 74-82.
[http://dx.doi.org/10.1016/j.intimp.2015.01.005] [PMID: 25601498]
[28]
Shafiey SI, Mohamed WR, Abo-Saif AA. Paroxetine and rivastigmine mitigates adjuvant-induced rheumatoid arthritis in rats: Impact on oxidative stress, apoptosis and RANKL/OPG signals. Life Sci 2018; 212: 109-18.
[http://dx.doi.org/10.1016/j.lfs.2018.09.046] [PMID: 30267788]
[29]
Nazari-Robati M, Akbari M, Khaksari M, Mirzaee M. Trehalose attenuates spinal cord injury through the regulation of oxidative stress, inflammation and GFAP expression in rats. J Spinal Cord Med 2019; 42(3): 387-94.
[http://dx.doi.org/10.1080/10790268.2018.1527077] [PMID: 30513271]
[30]
Akbari M, Dabiri S, Moeini-Aghtaei MM, Nazari-Robati M. Thermostabilized chondroitinase ABC promotes neuroprotection after contusion spinal cord injury. J Kerman Univ Med Sci 2020; 27(5): 369-79.
[31]
He Q, Wang Y, Lin W, et al. Trehalose alleviates PC12 neuronal death mediated by lipopolysaccharide-stimulated BV-2 cells via inhibiting nuclear transcription factor NF-κB and AP-1 activation. Neurotox Res 2014; 26(4): 430-9.
[http://dx.doi.org/10.1007/s12640-014-9487-7] [PMID: 25125332]
[32]
Taya K, Hirose K, Hamada S. Trehalose inhibits inflammatory cytokine production by protecting IκB-α reduction in mouse peritoneal macrophages. Arch Oral Biol 2009; 54(8): 749-56.
[http://dx.doi.org/10.1016/j.archoralbio.2009.05.003] [PMID: 19505677]
[33]
Tong Z, Cheng L, Song J, et al. Therapeutic effects of Caesalpinia minax Hance on complete Freund’s adjuvant (CFA)-induced arthritis and the anti-inflammatory activity of cassane diterpenes as main active components. J Ethnopharmacol 2018; 226: 90-6.
[http://dx.doi.org/10.1016/j.jep.2018.08.011] [PMID: 30114517]
[34]
Jamialahmadi T, Emami F, Bagheri RK, et al. The effect of trehalose administration on vascular inflammation in patients with coronary artery disease. Biomed Pharmacother 2022; 147: 112632.
[http://dx.doi.org/10.1016/j.biopha.2022.112632] [PMID: 35045351]
[35]
Mobini M, Radbakhsh S, Kubaski F, et al. Impact of intravenous trehalose administration in patients with niemann–pick disease types A and B. J Clin Med 2022; 11(1): 247.
[http://dx.doi.org/10.3390/jcm11010247] [PMID: 35011993]
[36]
Ganjali S, Jamialahmadi T, Abbasifard M, et al. Trehalose-induced alterations in serum expression levels of microRNAs associated with vascular inflammation in patients with coronary artery disease - the pilot results from the randomized controlled trial. Arch Med Sci 2022.
[http://dx.doi.org/10.5114/aoms/154987]
[37]
Hashemian S, Shojaei M, Radbakhsh S, et al. The effects of oral trehalose in patients with diabetes: A pilot randomized controlled trial. Arch Med Sci 2023.
[http://dx.doi.org/10.5114/aoms/159048]
[38]
Radbakhsh S, Mobini M, Gumpricht E, Banach M, Jamialahmadi T, Sahebkar A. The effect of intravenous trehalose administration in a patient with multiple sulfatase deficiency: A case study. Arch Med Sci 2023.
[http://dx.doi.org/10.5114/aoms/159711]