HISTOPATHOLOGICAL ANALYSIS OF THE INHIBITORY EFFECT OF IBUPROFEN ON AMYLOIDOGENESIS IN A MOUSE MODEL
DOI:
https://doi.org/10.26873/SVR-1901-2024Keywords:
amyloid A, amyloidosis, casein, ibuprofen, mouse modelAbstract
Amyloidosis represents a group of diseases, all characterized by the deposition of protein fibrils with a β-sheet structure. To evaluate the effects of ibuprofen on the inhibition of amyloid deposition, we used an animal model of experimental amyloid A amyloidosis. BALB/c mice (n = 30) were divided into two groups (n = 15 mice/group). Both the treatment and control groups received casein solution for 3 weeks to induce experimental amyloidosis, and ibuprofen was added to the drinking water of the treatment group simultaneously. After 3 weeks, all mice were euthanized. Tissue samples of various organs were collected, fixed, and processed for routine histopathological examination. This revealed amyloid deposition as an amorphous, homogenous, and eosinophilic substance in the control group’s renal glomeruli, hepatic parenchyma, and splenic vascular walls. In the treatment group, only mild amyloid deposition was observed in renal glomeruli and occasionally in the vascular wall of other tissues. The amount of amyloid deposition in the liver and kidneys in the treatment group was significantly lower than in the control group. Our results suggest that ibuprofen may prevent amyloid formation and accumulation in mice, especially in the kidneys and liver.
Histopatološka analiza zaviralnega učinka ibuprofena na amiloidogenezo na mišjem modelu
Izvleček: Amiloidoza predstavlja skupino bolezni, za katere je značilno odlaganje beljakovinskih fibril s strukturo β-ploskve. Za oceno učinkov ibuprofena na zaviranje odlaganja amiloida smo uporabili živalski model eksperimentalne amiloidoze amiloida A. Miši BALB/c (n = 30) smo razdelili v dve skupini (n = 15 miši/skupina). Tako zdravljena kot kontrolna skupina sta tri tedne prejemali raztopino kazeina za indukcijo eksperimentalne amiloidoze, hkrati pa je bil pitni vodi zdravljene skupine dodan ibuprofen. Po treh tednih so vse miši evtanazirali. Vzorci tkiva različnih organov so bili zbrani, fiksirani in obdelani za rutinsko histopatološko preiskavo. Ta je pokazala odlaganje amiloida kot amorfne, homogene in eozinofilne snovi v ledvičnih glomerulih, jetrnem parenhimu in žilnih stenah vranice kontrolne skupine. V skupini, ki je bila zdravljena, je bilo v ledvičnih glomerulih in občasno v žilni steni drugih tkiv opaženo le blago nalaganje amiloida. Količina odloženega amiloida v jetrih in ledvicah v tej skupini je bila bistveno manjša kot v kontrolni skupini. Naši rezultati kažejo, da lahko ibuprofen prepreči nastajanje in kopičenje amiloida pri miših, zlasti v ledvicah in jetrih.
Ključne besede: amiloid A; amiloidoza; kazein; ibuprofen; mišji model
References
Adams HR. Anti-inflammatory Drugs. In: Adams HR, ed. Veterinary Pharmacology and Therapeutics. 7th ed. Ames: Iowa State University Press 1995: 660–6.
Bachmanov AA, Reed DR, Beauchamp GK, Tordoff MG. Food intake, water intake, and drinking spout side preference of 28 mouse strains. Behav Genet 2002; 32(6): 435–43. doi: 10.1023/a:1020884312053
Brunton LL, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill Education, 1996: 981-86.
Cohen AS, Shirahama T. Animal model for human disease: spontaneous and induced amyloidosis. Am J Pathol 1972; 68(2): 441–4.
Cunnane G. Amyloid precursors and amyloidosis in inflammatory arthritis. Curr Opin Rheumatol 2001; 13(1): 67–73. doi: 10.1097/00002281-200101000-00011
Friman C, Pettersson T. Amyloidosis. Curr Opin Rheumatol 1996; 8(1): 62–71. doi: 10.1097/00002281-199601000-00012
Golden BD, Abramson SB. Selective cyclooxygenase-2 inhibitors. Rheum Dis Clin North Am 1999; 25(2): 359–78. doi: 10.1016/s0889-857x(05)70073-9
Grateau G, Jéru I, Rouaghe S, et al. Amyloidosis and auto-inflammatory syndromes. Curr Drug Targets Inflamm Allergy 2005; 4(1): 57–65. doi: 10.2174/1568010053622786
Guo J, Yu J, Grass D, et al. Inflammation-dependent cerebral deposition of serum amyloid a protein in a mouse model of amyloidosis. J Neurosci 2002; 22(14): 5900–9. doi: 10.1523/JNEUROSCI.22-14-05900.2002
Hardy J, Allsop D. Amyloid deposition as the central event in the etiology of Alzheimer’s disease. Trends Pharmacol Sci 1991; 12(10): 383–8. doi: 10.1016/0165-6147(91)90609-v
Hazenberg BPC, Van Gameren II, Bijzet J, Jager PL, van Rijswijk MH. Diagnostic and therapeutic approach of systemic amyloidosis. Neth J Med 2004; 62(4): 121–8.
Husebekk A, Stenstad T. Experimental AA-amyloidosis in mice is inhibited by treatment with the anti-rheumatic drug tenidap. Scand J Immunol 1996; 43(5): 551–5. doi: 10.1046/j.1365-3083.1996.d01-74.x
Lim GP, Yang F, Chu T, et al. Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer’s disease. J Neurosci 2000; 20(15): 5709–14. doi: 10.1523/JNEUROSCI.20-15-05709.2000
Muchtar E, Dispenzieri A, Magen H, et al. Systemic amyloidosis from A (AA) to T (ATTR): a review. J Intern Med 2021; 289(3): 268–92. doi: 10.1111/joim.13169
Nakamura T. Clinical strategies for amyloid A amyloidosis secondary to rheumatoid arthritis. Modern Rheumatol 2008; 18(2): 109–18. doi: 10.3109/s10165-008-0035-2
Narváez J, Hernández MV, Ruiz JM, Vaquero CG, Juanola X, Nollaa JM. Rituximab therapy for AA-Amyloidosis secondary to rheumatoid arthritis. Joint Bone Spine 2011; 78(1):101–3. doi: 10.1016/j.jbspin.2010.09.020
Pepys M, Hawkins P. Amyloidosis. In: Warrell D, eds. Textbook of medicine. 4th ed. Oxford: Oxford University Press , 2003: 162–73.
Pettersson T, Konttinen YT, Maury CPJ. Treatment strategies for amyloid A amyloidosis. Expert Opin Pharmacother 2008; 9(12): 2117–28. doi: 10.1517/14656566.9.12.2117
Shirahama T, Cohen AS. Redistribution of Amyloid Deposits. Am J Pathol 1980; 99(3): 539–50.
Sipe JD, Bartle LM, Loose LD. Modification of proinflammatory cytokine production by the antirheumatic agents tenidap and naproxen. A possible correlate with clinical acute phase response. J Immunol 1992; 148(2): 480–4.
Sipe JD, Cohen AS. Review: history of the amyloid fibril. J Struct Biol 2000; 130(2/3): 88–98. doi: 10.1006/jsbi.2000.4221
Sipe JD. Amyloidosis. Annu Rev Biochem 1992; 61: 947–75. doi: 10.1146/annurev.bi.61.070192.004503
Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet 2016: 387(10038): 2641–54. doi: 10.1016/S0140-6736(15)01274-X
World Health Organization. WHO Model Lists of Essential Medicines. Geneva: WHO, 2023. https://www.who.int/groups/expert-committee-on-selection-and-use-of-essential-medicines/essential-medicines-lists. (16. 7. 2023)
Yao Y, Chinnici C, Tang H, et al. Brain inflammation and oxidative stress in a transgenic mouse model of Alzheimer-like brain amyloidosis. J Neuroinflammation 2004; 1(1): 21. doi: 10.1186/1742-2094-1-21
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Seyedian Moghaddam Atieh, Mohammad Azizzadeh, Ahmadreza Movasseghi
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
