Efecto del meloxicam y el Flunixin meglumina sobre algunos parámetros renales en ratas macho geriátricas

• Ahmet Ufuk Komuroglu Van Yuzuncu Yıl University, Health Service Vocational School of Higher Education. Van, Türkiye
• Yıldıray Basbugan Yuzuncu Yil University, Internal Medicine, Faculty of Veterinary Medicine. Van, Türkiye
• Nazmi Yuksek Yuzuncu Yil University, Internal Medicine, Faculty of Veterinary Medicine. Van, Türkiye
• Nuri Altug Necmettin Erbakan University, Veterinary Faculty. Konya, Türkiye
• Ugur Ozdek Van Yuzuncu Yıl University, Health Service Vocational School of Higher Education. Van, Türkiye
• Semiha Dede Van Yuzuncu Yıl University, Department of Biochemistry, Faculty of Veterinary Medicine. Van, Türkiye

DOI: https://doi.org/10.52973/rcfcv-e34428

Palabras clave: Rata geriátrica, Meloxicam, Flunixin Meglumina, KIM–1, NGAL, CYS–C, riñón

Resumen

La edad avanzada, llamada geriatría, tiene efectos negativos sobre los cambios fisiológicos que se producen con el envejecimiento en los sistemas. Se sabe que los fármacos no esteroides utilizados en edades geriátricas tienen efectos negativos sobre los riñones. Para ello, en este estudio; se evaluaron los efectos del Meloxicam y el Flunixin Meglumina, fármacos no esteroides frecuentemente preferidos en Medicina Vveterinaria, sobre los riñones de ratas geriátricas. En el estudio se utilizaron 24 ratas geriátricas macho y 24 ratas albinas Wistar macho jóvenes de 3 meses de edad. Se crearon 6 grupos, con 8 ratas en cada grupo: control joven (YC), Meloxicam joven (YM), Flunixin Meglubina joven (YFM), control geriátrico (GC), Meloxicam geriátrico (GM) y Flunixino Meglubina geriátrico (GFM). No se adminsitro ningun farmaco a los grupo YC y GC. Se administraron 5,8 mg·kg^-1 de meloxicam a los grupos YM y GM y 2,5 mg·kg^-1 de flunixima meglubina por vía intraperitoneal a los grupos YFM y GFM durante 5 días. Lipocalina asociada a gelatinasa de neutrófilos (NGAL), cistatina C (Cyc–c), molécula de lesión renal–1 (KIM–1) e interleucina–18 (IL–18), urea, creatinina (Crea), albúmina (Alb) y proteína total (TP), que son marcadores de daño renal a partir de las muestras de suero y orina obtenidas, se midieron. Se encontró que los niveles séricos de NGAL, Cys–C y KIM–1 en el grupo GC fueronsignificativamente más altos que los del grupo YC (P<0,05). La administración de ambos fármacos provocó un aumento de los niveles séricos de Cyc–c y NGAL tanto en ratas jóvenes como geriátricas (P<0,05). Dado que tanto la administración de meloxicam como de flunixina meglubina provocan un aumento de los niveles de NGAL y Cys–c en ratas jóvenes y geriátricas, se puede considerar como medida preventiva ajustar la dosis del fármaco y el tiempo de aplicación mediante la evaluación de las funciones renales iniciales antes de iniciar la terapia.

Citas

Bellows J, Center S, Daristotle L, Estrada AH, Flickinger EA, Horwitz DF, Lascelles BDX, Lepine A, Perea S, Scherk M, Shoveller AK. Evaluating aging in cats: how to determine what is healthy and what is disease. J. Feline Med. Surg. [Internet]. 2016; 18(7):551–570. doi: https://doi.org/f8v455

Haydardedeoğlu A, Kalınbacak A. Geriatrik hasta köpeklerde fiziksel, biyokimyasal ve radyolojik bulguların değerlendirilmesi [The Assessments of Physical, Biochemical and Radiological Findings in the Geriatric Patient Dogs]. Ataturk Univ. Vet. Bil. Derg. [Internet]. 2015; 10(2):93–101. Turkish. doi: https://doi.org/gt9gjs

Quinn R. Comparing rat’s to human’s age: how old is my rat in people years? Nutrition [Internet]. 2005; 21(6):775–777. doi: https://doi.org/cz3qj7

Koşal V, Keleş ÖF, Kömüroğlu AU, Basbugan Y. Investigation of Reproductive Parameters in Male Geriatric (3 years old) Rats. Van Vet. J. [Internet]. 2023; 34(2):174–179. doi: https://doi.org/gt9gjt

Basbugan Y, Yüksek N, Kömüroğlu A, Okman EN, Ozdek U. Some Renal Marker Levels in Geriatric Rats. Van Vet. J. [Internet]. 2023; 34(3):213–218. doi: https://doi.org/gt9gjv

Thomas SE, Anderson S, Gordon KL, Oyama TT, Shankland SJ, Johnson RJ. Tubulointerstitial disease in aging: evidence for underlying peritubular capillary damage, a potential role for renal ischemia. J. Am. Soc. Nephrol. [Internet]. 1998; 9(2):231–242. doi: https://doi.org/gt9gjw

Davies M. Geriatric clinics in practice. Vet. Focus. 2012;22(2):15–22.

KuKanich K, George C, Roush JK, Sharp S, Farace G, Yerramilli M, Peterson S, Grauer GF. Effects of low–dose meloxicam in cats with chronic kidney disease. J. Feline Med. Surg. [Internet]. 2021; 23(2):138–148. doi: https://doi.org/gnczmx

Whelton A. Renal and related cardiovascular effects of conventional and COX–2–specific NSAIDs and non–NSAID analgesics. Am. J. Ther. [Internet]. 2000; 7(2):63–74. doi: https://doi.org/dq8kmk

Kim S, Joo KW. Electrolyte and Acid–base disturbances associated with non–steroidal anti–inflammatory drugs. Electrolyte Blood Press. [Internet]. 2007; 5(2):116–125. doi: https://doi.org/dvh3s4

VanderBrink BA, Asanuma H, Hile K, Zhang H, Rink RC, Meldrum KK. Interleukin–18 stimulates a positive feedback loop during renal obstruction via interleukin–18 receptor. J. Urol. [Internet]. 2011; 186(4):1502–1508. doi: https://doi.org/djm2gz

Chiang CK, Hsu SP, Pai MF, Peng YS, Ho TI, Liu SH, Hung KY, Tsai TJ, Hsieh BS. Plasma interleukin–18 levels in chronic renal failure and continuous ambulatory peritoneal dialysis. Blood Purif. [Internet]. 2005; 23(2): 144–148. doi: https://doi.org/fw3436

Parikh CR, Abraham E, Ancukiewicz M, Edelstein CL. Urine IL–18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit. J. Am. Soc. Nephrol. [Internet]. 2005; 16(10):3046–3052. doi: https://doi.org/bqbkdk

Bombardieri M, McInnes IB, Pitzalis C. Interleukin–18 as a potential therapeutic target in chronic autoimmune/inflammatory conditions. Expert Opin. Biol. Ther. [Internet]. 2007; 7(1):31–40. doi: https://doi.org/fkw62p

Nakahira M, Ahn HJ, Park WR, Gao P, Tomura M, Park CS, Hamaoka T, Ohta T, Kurimoto M, Fujiwara H. Synergy of IL–12 and IL–18 for IFN–γ gene expression: IL–12–induced STAT4 contributes to IFN–γ promoter activation by up–regulating the binding activity of IL–18–induced activator protein 1. J. Immunol. [Internet]. 2002; 168(3):1146–1153. doi: https://doi.org/gj39ms

Al–Naimi MS, Rasheed HA, Hussien NR, Al–Kuraishy HM, Al–Gareeb AI. Nephrotoxicity: Role and significance of renal biomarkers in the early detection of acute renal injury. J. Adv. Pharm. Technol. Res. [Internet]. 2019; 10(3):95–99. doi: https://doi.org/gtsw8s

Bianchi M, Panerai AE. Effects of lornoxicam, piroxicam, and meloxicam in a model of thermal hindpaw hyperalgesia induced by formalin injection in rat tail. Pharm. Res. [Internet]. 2002; 45(2): 101–105. doi: https://doi.org/fwcpcw

Erpek S, Kilic N, Kozaci D, Dikicioglu E, Kavak T. Effects of flunixin meglumine, diclofenac sodium and metamizole sodium on experimental wound healing in rats. Revue Méd. Vét. [Internet]. 2006 [cited 12 Feb. 2024]; 157(4):185–192. Available in: https://goo.su/y1NxfL0

Tubbs JT, Kissling GE, Travlos GS, Goulding DR, Clark JA, King–Herbert AP, Blankenship–Paris TL. Effects of buprenorphine, meloxicam, and flunixin meglumine as postoperative analgesia in mice. J. Am. Assoc. Lab. Anim. Sci. [Internet]. 2011 [cited 12 Feb. 2024]; 50(2):185–191 Available in: https://goo.su/yEfFUcd

Durrance SA. Older adults and NSAIDs: avoiding adverse reactions. Geriatr. Nurs. [Internet]. 2003; 24(6):348–352. doi: https://doi.org/fn9hsf

Knox DM, Martof MT. Effects of drug therapy on renal function of healthy older adults. J. Gerontol. Nurs. [Internet]. 2013; 21(4):35–40. doi: https://doi.org/gt9gjx

Amatruda JG, Katz R, Peralta CA, Estrella MM, Sarathy H, Fried LF, Newman AB, Parikh CR, Ix JH, Sarnak MJ, Shlipak MG. Association of Non‐Steroidal Anti‐Inflammatory Drugs with Kidney Health in Ambulatory Older Adults. J. Am. Geriatr. Soc. [Internet]. 2021; 69(3):726–734. doi: https://doi.org/gt9gjz

Griffin MR, Yared A, Ray WA. Nonsteroidal antiinflammatory drugs and acute renal failure in elderly persons. Am. J. Epidemiol. [Internet]. 2000; 151(5):488–496. doi: https://doi.org/gt9gj2

Alorabi M, Cavalu S, Al–Kuraishy HM, Al–Gareeb AI, Mostafa–Hedeab G, Negm WA, Youssef A, El–Kadem AH, Saad HM, Batiha GE. Pentoxifylline and berberine mitigate diclofenac–induced acute nephrotoxicity in male rats via modulation of inflammation and oxidative stress. Biomed. Pharmacother. [Internet]. 2022; 152:113225. doi: https://doi.org/gt9gj3

Buonafine M, Martinez–Martinez E, Jaisser F. More than a simple biomarker: the role of NGAL in cardiovascular and renal diseases. Clin. Sci. [internet]. 2018; 132(9):909–923. doi: https://doi.org/gdkgbs

Oz K, Gode S, Basgoze S, Koser M, Oz A, Göksel OS, Yeniterzi M, Bakir I. Cystatin C and NGAL as Biomarkers for Early Detection of Acute Kidney Injury in Geriatrics. Int. Surg. [Internet]. 2016; 101(7–8):390–398. doi: https://doi.org/gbp4x7

Liu F, Yang H, Chen H, Zhang M, Ma Q. High expression of neutrophil gelatinase–associated lipocalin (NGAL) in the kidney proximal tubules of diabetic rats. Adv. Med. Sci. [Internet]. 2015; 60(1):133–138. doi: https://doi.org/gtd68g

Marakala V. Neutrophil gelatinase–associated lipocalin (NGAL) in kidney injury–A systematic review. Clin Chim Acta . [Internet]. 2022; 536(1):135–141. doi: https://doi.org/gtbf98

Nehus E, Kaddourah A, Bennett M, Pyles O, Devarajan P. Subclinical kidney injury in children receiving nonsteroidal anti–inflammatory drugs after cardiac surgery. J. Pediatr. [Internet]. 2017; 189:175–180. doi: https://doi.org/gcqr73

Zhang Z, Lu B, Sheng X, Jin N. Cystatin C in prediction of acute kidney injury: a systemic review and meta-analysis. Am. J. Kidney Dis. [Internet]. 2011; 58(3):356-365. doi: https://doi.org/cbx7mm

Togashi Y, Miyamoto Y. Urinary cystatin C as a biomarker for diabetic nephropathy and its immunohistochemical localization in kidney in Zucker diabetic fatty (ZDF) rats. Exp. Toxicol. Pathol. [Internet]. 2013; 65(5):615–622. doi: https://doi.org/gt9gj4

Munikrishnappa D. Chronic kidney disease (CKD) in the elderly–a geriatrician’s perspective. Aging Male [Internet]. 2007; 10(3):113–137. doi: https://doi.org/dfgfsz

Shukla A, Rai MK, Prasad N, Agarwal V. Short–term non–steroid anti–inflammatory drug use in spondyloarthritis patients induces subclinical acute kidney injury: biomarkers study. Nephron [Internet]. 2017; 135(4):277–286. doi: https://doi.org/f9xkdv

Vaidya VS, Ferguson MA, Bonventre JV. Biomarkers of acute kidney injury. Annu. Rev. Pharm. Toxicol. [Internet]. 2008; 48:463–493. doi: https://doi.org/dd7m6h

Melnikov VY, Ecder T, Fantuzzi G, Siegmund B, Lucia MS, Dinarello CA, Schrier RW, Edelstein CL. Impaired IL–18 processing protects caspase–1–deficient mice from ischemic acute renal failure. J. Clin. Invest. [Internet]. 2001; 107(9):1145–1152. https://doi.org/fv8twp

Wu H, Craft ML, Wang P, Wyburn KR, Chen G, Ma J, Hambly B, Chadban SJ. IL–18 contributes to renal damage after ischemia–reperfusion. J. Am. Soc. Nephrol. [Internet]. 2008; 19(12):2331–2341. doi: https://doi.org/c6qsc7

Sahu N, Mishra G, Chandra HK, Nirala SK, Bhadauria M. Naringenin mitigates antituberculosis drugs induced hepatic and renal injury in rats. J. Tradit. Complement. Med. [Internet]. 2020; 10(1):26–35. doi: https://doi.org/gmdvb3

Sepulveda JL. Challenges in Routine Clinical Chemistry Testing: Analysis of Small Molecules. In: Dasgupta A, Sepulveda JL, editors. Accurate Results in the Clinical Laboratory [Internet]. Amsterdam: Elsevier; 2013. p. 93–129. doi: https://doi.org/nfx9

Padma S, Sundaram PS. Determining an accurate method to estimate GFR in renal transplant recipients with stable serum creatinine levels. Iran. J. Nucl. Med. [Internet]. 2020 [cited 2 Jan. 2024]; 28(1):21–27. Available in: https://goo.su/pmUv

Moradi A, Abolfathi M, Javadian M, Heidarian E, Roshanmehr H, Khaledi M, Nouri A. Gallic acid exerts nephroprotective, anti–oxidative stress, and anti–inflammatory effects against diclofenac–induced renal injury in male rats. Arch. Med. Res. [Internet]. 2021; 52(4):380–388. doi: https://doi.org/gmdvc2

Borges M, Marini Filho R, Laposy CB, Guimarães–Okamoto PTC, Chaves MP, Vieira ANLS, Melchert A. Nonsteroidal anti–inflammatory therapy: changes on renal function of healthy dogs. Acta Cir. Bras. [Internet]. 2013; 28(12):842–847. doi: https://doi.org/gt9gj5