Effect of anakinra, tocilizumab, and the combination thereof on bladder ischemia- reperfusion damage in albino Wistar-type rats.

Efecto de la anakinra, el tocilizumab y la combinación de ambos sobre el daño por isquemia-reperfusión vesical en ratas albinas tipo Wistar.

• Senol Bicer Erzincan Binali Yildirim University, Erzincan, Turkey. https://orcid.org/0000-0002-6380-4861
• Bahadir Suleyman Erzincan Binali Yildirim University, Erzincan, Turkey. https://orcid.org/0000-0001-5795-3177
• Renad Mammadov Erzincan Binali Yildirim University, Erzincan, Turkey. https://orcid.org/0000-0002-5785-1960
• Bulent Yavuzer Erzincan Binali Yildirim University, Erzincan, Turkey https://orcid.org/0000-0001-7576-0678
• Betul Cicek Erzincan Binali Yildirim University, Erzincan, Turkey https://orcid.org/0000-0003-1395-1326
• Durdu Altuner Erzincan Binali Yildirim University, Erzincan, Turkey https://orcid.org/0000-0002-5756-3459
• Taha A. Coban Erzincan Binali Yildirim University, Erzincan, Turkey. https://orcid.org/0000-0003-1711-5499
• Halis Suleyman Erzincan Binali Yildirim University, Erzincan, Turkey. https://orcid.org/0000-0002-9239-4099

DOI: https://doi.org/10.54817/IC.v64n3a9

Palabras clave: anakinra, combinación de anakinra y tocilizumab, vejiga, daño por isquemia-reperfusión, ratas, tocilizumab

Resumen

Varios estudios han demostrado que el estrés oxidativo, y las citocinas proinflamatorias tales como el factor de necrosis tumoral alfa (TNF-α), la interleucina uno beta (IL-1β) y la interleucina seis (IL-6) son los principales factores subyacentes al daño por isquemia-reperfusión (I/R) vesical. Se sabe que la anakinra y el tocilizumab son antioxidante e inhibidores de las citocina proinflamatorias. Nuestro estudio pretende investigar si la anakinra, el tocilizumab y la combinación (ATC) de ambos tienen un efecto protector contra el daño oxidativo e inflamatorio de la vejiga inducido mediante el procedimiento de I/R en ratas, y evaluarlo mediante la comparación de estos compuestos. Se dividieron a ratas macho en cinco grupos: un grupo sometido a la operación simulada (SG); un grupo al cual solo se aplicó I/R a la vejiga (IRG); un grupo al cual se aplica el procedimiento I/R a la vejiga + anakinra (AIR); un grupo en el que se aplica el procedimiento I/R a la vejiga + tocilizumab (TIR); y un grupo en el que se aplica el procedimiento I/R a la vejiga + ATC (ATIR). Se colocó una pinza atraumática en la aorta abdominal de los animales de todos los grupos (excepto SG), y se realizó una hora de isquemia seguida de dos horas de reperfusión. Nuestros hallazgos bioquímicos mostraron que la anakinra y el tocilizumab inhibieron significativamente el aumento del malondialdehído oxidante (MDA) y la disminución de antioxidantes como el glutatión total (tGSH), la superóxido dismutasa (SOD) y la catalasa (CAT) en el tejido de la vejiga por I/R, ambos a los mismos niveles. Además, la anakinra y el tocilizumab suprimieron significativamente el aumento de TNF-α, IL-1β e IL-6 asociado a la I/R en el tejido vesical. La combinación ATC fue la que mejor previno el aumento de MDA, TNF-α, IL-1β e IL-6 relacionado con la I/R y la disminución de tGSH, SOD y CAT en el tejido vesical. La ATC resultó más beneficiosa que la anakinra o el tocilizumab solos en el tratamiento del daño por I/R de la vejiga.

Citas

Levin RM, Leggett R, Whitbeck C, Horan P. Effect of calcium and calcium chelator on the response of the bladder to in vitro ischaemia. Br J Urol 1998; 82(6): 882-887. https://doi.org/10.1046/j.1464- 410x.1998.00891.x

Parekh MH, Lobel R, O’Connor LJ, Leggett RE, Levin RM. Protective effect of vitamin E on the response of the rabbit bladder to partial outlet obstruction. J Urol 2001; 166(1): 341-346. PMID: 11435897

Matsumoto S, Hanai T, Yoshioka N, Shimizu N, Sugiyama T, Uemura H, Levin RM. Edaravone protects against ischemia/ reperfusion-induced functional and bio-chemical changes in rat urinary bladder. Urology 2005; 66(4): 892-896. https://doi. org/10.1016/j.urology.2005.04.035

Thurmond P, Yang JH, Azadzoi KM. LUTS in pelvic ischemia: a new concept in voiding dysfunction. Am J Physiol Renal Physiol 15 2016; 310(8): F738-F743. https:// doi.org/10.1152/ajprenal.00333.2015

Shin JH, Chun KS, Na YG, Song KH, Kim SI, Lim JS, Kim GH. Allopurinol protects against ischemia/reperfusion-induced injury in rat urinary bladders. Oxid Med Cell Longev 2015; 2015: 906787. https://doi. org/10.1155/2015/906787

Shin JH, Kim GH, Song KH, Na YG, Sul CK, Lim JS. Protective effect of N-acetyl- cysteine against ischemia/reperfusion injury in rat urinary bladders. Cell Biochem Funct 2014; 32(1): 24-30. https://doi. org/10.1002/cbf.2967

Altunkaynak-Camca HO, Yazihan N. The pretreatment of rats with nebivolol ameliorates bladder contractile dysfunction caused by ischemia-reperfusion injury. Low Urin Tract Symptoms 2021; 13(1): 183-188. https://doi.org/10.1111/luts.12338

Oka M, Fukui T, Ueda M, Tagaya M, Oyama T, Tanaka M. Suppression of bladder oxidative stress and inflammation by a phytotherapeutic agent in a rat model of partial bladder outlet obstruction. J Urol 2009; 182(1): 382-390. https://doi. org/10.1016/j.juro.2009.02.104

Affas ZR, Rasool BQ, Sr., Sebastian SA, Affas RS, Mohamadtahr SK, Saoor NH, Mohammad AN, Saoor GH, Husain BA, Touza R, Touza G, Amen S, Nazzaro W. Rilonacept and anakinra in recurrent pericarditis: a systematic review and meta-analysis. Cureus 2022; 14(11): e31226. https://doi.org/10.7759/cureus.31226

Anakinra. Drugs and Lactation Database (LactMed(R)). National Institute of Child Health and Human Development; 2006. 30 Nov 2022. PMID: 30000931.

Cheema AH, Chaludiya K, Khalid M, Nwosu M, Konka S, Agyeman WY, Bisht A, Gopinath A, Arcia Franchini AP. Efficacy of anakinra in pericarditis: a systematic review. Cureus 2022; 14(10): e29862.https://doi.org/10.7759/cureus.29862.
Hirik E, Suleyman B, Mammadov R, Yapanoglu T, Cimen FK, Cetin N, Kurt N. Effect of anakinra, an interleukin one beta antagonist, on oxidative testicular damage induced in rats with ischemia reperfusion. Rev Int Androl 2018; 16(3): 87-94. https:// doi.org/10.1016/j.androl.2017.03.001

Nayki UA, Nayki C, Cetin N, Cimen FK, Coban A, Mammadov R, Tas IH, Malkoc Effect of Kineret(R) on ovarian ischemia reperfusion injury in a rat model. J Obstet Gynaecol Res 2016; 42(11): 1525-1533. https://doi.org/10.1111/jog.13095.

Sebba A. Tocilizumab: the first interleukin-6-receptor inhibitor. Am J Health Syst Pharm 2008; 65(15): 1413-1418. https://doi.org/10.2146/ajhp070449.

Preuss CV, Anjum F. Tocilizumab. Stat- Pearls [Internet]. © 2022, StatPearls Publishing LLC.; 2023. Jan 2022. PMID: 34033406.

Erdem KTO, Bedir Z, Kuyrukluyildiz U, Tas HG, Suleyman Z, Bulut S, Mendil AS, Sarigul C, Unver E, Suleyman H. Effect of tocilizumab on ischemia reperfusion- induced oxido-inflammatory renal damage and dysfunction in rats. Exp Anim 2022; 71(4): 491-499. https://doi.org/10.1538/expanim.22-0034.

Demiryilmaz I, Turan MI, Kisaoglu A, Gulapoglu M, Yilmaz I, Suleyman H. Protective effect of nimesulide against hepatic ischemia/reperfusion injury in rats: effects on oxidant/antioxidants, DNA mutation and COX-1/COX-2 levels. Pharmacol Rep 2014; 66(4): 647-652. https://doi. org/10.1016/j.pharep.2014.02.015

Goth L. A simple method for determination of serum catalase activity and revision of reference range. Clin Chim Acta 1991; 196(2-3): 143-151. https://doi. org/10.1016/0009-8981(91)90067-m

Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254. https://doi.org/10.1006/ abio.1976.9999

Suleyman H, Ozcicek A. Molecular mechanism of ischemia reperfusion injury. Arch Basic Clin Res 2019; 2(1): 25-27. https://doi.org/10.5152/abcr.2019.31

Radu F, Leggett RE, Schuler C, Levin RM. The effect of in vitro ischemia/reperfusion on contraction, free fatty acid content, phospholipid content, and malondialdehyde levels of the rabbit urinary bladder. Mol Cell Biochem 2011; 346(1-2): 179-186. https://doi.org/10.1007/s11010-010-0603-6.

Matsui T, Oka M, Fukui T, Tanaka M, Oyama T, Sagawa K, Nomiya M, Yamaguchi O. Suppression of bladder overactivity and oxidative stress by the phytotherapeutic agent, Eviprostat, in a rat model of atherosclerosis-induced chronic bladder is chemia. Int J Urol 2012; 19(7): 669-675. https://doi.org/10.1111/j.1442-2042. 2012.03000.x

Kandemir M, Yasar NF, Ozkurt M, Ozyurt R, Bektur Aykanat NE, Erkasap N. The role of anakinra in the modulation of intestinal cell apoptosis and inflammatory response during ischemia/reperfusion. Turk J Med Sci 2021; 51(4): 2177-2184. https:// doi.org/10.3906/sag-2008-258

Callaghan CM, Schuler C, Leggett RE, Levin RM. Effect of severity and duration of bladder outlet obstruction on catalase and superoxide dismutase activity. Int J Urol 2013; 20(11): 1130-1135. https://doi.org/10.1111/iju.12115.

Sandalio LM, Collado-Arenal AM, Romero-Puertas MC. Deciphering peroxisomal reactive species interactome and redox signalling networks. Free Radic Biol Med 2023; 197: 58-70. https://doi.org/10.1016/j.free- radbiomed.2023.01.014.

Wu YH, Chueh KS, Chuang SM, Long CY, Lu JH, Juan YS. Bladder hyperactivity induced by oxidative stress and bladder ischemia: a review of treatment strategies with antioxidants. Int J Mol Sci 2021; 22(11): https://doi.org/10.3390/ijms22116014.

Lin AD, Mannikarottu A, Kogan BA, Whitbeck C, Leggett RE, Levin RM. Effect of bilateral in vivo ischemia/reperfusion on the activities of superoxide dismutase and catalase: response to a standardized grape suspension. Mol Cell Biochem 2007; 296(1-2): 11-16. https://doi.org/10.1007/s11010-005-9068-4.

Kanno Y, Mitsui T, Kitta T, Moriya K, Tsukiyama T, Hatakeyama S, Nonomura K. The inflammatory cytokine IL -1beta is involved in bladder remodeling after bladder outlet obstruction in mice. Neurourol Urodyn 2016; 35(3): 377-381. https://doi.org/10.1002/nau.22721.

Butler DSC, Ambite I, Nagy K, Cafaro C, Ahmed A, Nadeem A, Filenko N, Tran TH, Andersson KE, Wullt B, Puthia M, Svanborg C. Neuroepithelial control of mucosal inflammation in acute cystitis. Sci Rep 2018; 8(1): 11015. https://doi. org/10.1038/s41598-018-28634-0.