Therapeutic and protective effects of montelukast against doxorubicin-induced acute kidney damage in rats

Document Type : Original Article

Authors

1 Department of Anatomy, School of Medicine, Inonu University, Malatya, Turkey

2 Department of Urology, School of Medicine, Inonu University, Malatya, Turkey

3 Department of Histology-Embryology, School of Medicine, Inonu University, Malatya, Turkey

4 Department of Emergency, School of Medicine, Inonu University, Malatya, Turkey

5 Department of Anesthesiology and Reanimation, School of Medicine, Inonu University, Malatya, Turkey

6 Department of Physiology, School of Medicine, Inonu University, Malatya, Turkey

7 Department of Anatomy, School of Medicine, Erciyes University, Kayseri, Turkey

Abstract

Objective(s): The current study was designed to investigate the therapeutic and protective effects of montelukast (ML) against doxorubicin (DOX)-induced acute kidney damage in rats.
Materials and Methods: Thirty-five Wistar albino female rats were randomly divided into 5 groups as follows: Group I: Control; Group II: Control+ML; Group III: DOX; Group IV: DOX+ML; Group V: ML+DOX. At the end of the experiment, the kidney tissues of rats were collected. Thiobarbituric acid reactive substance (TBARS), reduced glutathione, superoxide dismutase (SOD), and catalase levels were determined from the kidney tissues. In addition, the kidney tissues were examined histologically.
Results: DOX induced a significant increase in the kidney TBARS levels, whereas SOD contents significantly decreased when compared with the control group.  On the other hand, ML administration before and after DOX injection caused significant decreases in TBARS production and also increases in SOD levels. Histologically, the most remarkable damage was glomerulosclerosis and tubular changes in the DOX group. Moreover, marked tubular necrosis and swelling in tubular epithelial cells were observed in this group. Contrarily, although glomerulosclerosis was recognized as alleviated also in both DOX+ML and ML+DOX groups, the lesions did not completely ameliorate. However, treatment with ML after DOX injection was more effective than treatment with ML before DOX injection with respect to the protection of tubular structures.
Conclusion: It was determined that ML treatment after DOX injection caused therapeutic effects against DOX-induced kidney damage. Thence, ML treatment is of some clinical properties for oxidative stress damage in kidney tissues.

Keywords

Main Subjects


1. Fadillioglu E, Erdogan H, Sogut S, and Kuku I. Protective effects of erdosteine against doxorubicin-induced cardiomyopathy in rats. J Appl Toxicol, 2003; 23:71–74.
2. Cappetta D, Rossi F, Plegari E, Quaini F, Berrino L, Urbanek K, et al. Doxorubicin targets multiple players: A new view of an old problem. Pharmacol Res 2018; 127: 4-14.
3. Jovanovic D, Djukanovic I, Susic D, Funduk G, Jovanovic Z, Dragojlovic Z, et al. The effect of captopril on the development of adriamycin nephropathy in rats with spontaneous arterial hypertension. Srp Arh Celok Lek 1996; 9:1247.
4. Zhang Y, Xu Y, Qi Y, Xu L, Song S, Yin L et al. Protective effects of dioscin against doxorubicin induced nephrotoxicity via adjusting FXR-mediated oxidative stress and inflammation. Toxicol 2017; 378: 53-64.
5. Saad SY, Najjar TA, Al-Rikabi AC. The preventive role of deferoxamine against acute doxorubicin-induced cardiac,renal and hepatic toxicity in rats. Pharmacol Res 2001; 43:211–8.
6. Zhao L, Qi Y, Xu L, Tao X, Han X, Yin L, et al. MicroRNA-140-5p aggravates doxorubicin induced cardiotoxicity by promoting myocardial oxidative stress via targeting Nrf2 and Sirt2. Redox Biol 2018; 15: 284-296.
7. Liu LL, Li QX, Xia L, Li J, Shao L. Differential effects of dihydropyridine calcium antagonists on doxorubicin-induced nephrotoxicity in rats. Toxicol 2007; 231:81–90.
8. Karaman A, Fadillioglu E, Turkmen E, Tas E, Yilmaz Z. Protective effects of leflunomide against ischemia-reperfusion injury of the rat liver. Pediatr Surg Int 2006; 22:428–434.
9. Cuciureanu M, Caruntu ID, Paduraru O, Stoica B, Jerca L, Crauciuc E, et al. The protective effect of montelukast sodium on carbon tetrachloride induced hepatopathy in rat. Prostaglandins Other Lipid Mediat 2009; 88: 82-88.
10. Sener G, Sehirli O, Velioglu-Ogunc A, Cetinel S, Gedik N, Caner M, et al. Montelukast protects against renal ischemia/reperfusion injury in rats. Pharmacol Res 2006; 54: 65-71.
11. Damtew B, Marino JA, Fratianne RB, Spagnuolo PJ. Neutrophil lipoxygenase metabolism and adhesive function following acute thermal injury. J Lab Clin Med 1993; 121: 328-336.
12. Qu X, Chen Y, Yin C. Effect of montelukast on the expression of CD4+CD25+ regulatory T cells in children with acute bronchial asthma. Exp Ther Med. 2018;16:2381-2386.
13. Wallace JL, Beck PL, Morris GP. Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage? Am J Physiol 1988; 254: 117-123.
14. Mansour RM, Ahmed MAE, El-Sahar AE, El Sayed NS. Montelukast attenuates rotenone-induced microglial activation/p38 MAPK expression in rats: Possible role of its antioxidant, anti-inflammatory and antiapoptotic effects. Toxicol Appl Pharmacol 2018;15;358:76-85.
15. Sener G, Sakarcan A, Sehirli O, Eksioglu-Demiralp E, Sener E, Ercan F, et al. Chronic renal failure-induced multiple-organ injury in rats is alleviated by the selective CysLT1 receptor antagonist montelukast. Prostaglandins Other Lipid Mediat 2007; 83:257–267.
16. Kose E, Sapmaz HI, Sarihan E, Vardi N, Turkoz Y, Ekinci N. Beneficial effects of montelukast against methotrexate-induced liver toxicity: a biochemical and histological study. SCI  World J 2012;2012:987508.
17. Kose E, Beytur A, Vardi N, Turkoz Y, Ekinci N, Ekincioglu Z. The effects of montelukast against methotrexate-induced acute renal damage. Ann Med Res 2011; 18: 73–77.
18. Yagi K. Simple assay for the level of total lipid peroxides in serum or plasma. Methods Mol Biol 1998; 108:101–106.
19. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 1968; 25:192–205.
20. Sun Y, Oberley LW, Li YA. Simple method for clinical assay of superoxide dismutase. Clin Chem 1988; 34:497–500.
21. Aebi H. Catalase.  In: Bergmeyer HU (ed) In methods of enzymatic analysis. Academic Press, NY;1974.
22. Fujihara CK, Malherios DMAC, Zatz R, Noronha IL. Mycophenolate mofetil attenuates renal injury in the rat remnant kidney. Kidney Int 1998; 54:1510–1519.
23. Ibrahim MA, Ashour OM, Ibrahim YF, El-Bitar HI, Gomaa W, Abdel-Rahim SR. Angiotensin-converting enzyme inhibition and angiotensin AT(1)-receptor antagonism equally improve doxorubicin-induced cardiotoxicity and nephrotoxicity. Pharmacol Res. 2009; 60:373-381.
24-Oz E, Ilhan MN. Effects of melatonin in reducing the toxic effects of doxorubicin. Mol Cell Biochem 2006; 286:11–15.
25. Usta Y, Ismailoglu UB, Bakkaloglu A, Orhan D, Besbas N, Sahin-Erdemli I, et al. Efects of pentoxifylline in adriamycin-induced renal disease in rats. Pediatr Nephrol 2004; 19: 840–843.
26. Rashid S, Ali N, Nafees S, Ahmad ST, Arjumand W, Hasan SK, Sultana S. Alleviation of doxorubicin-induced nephrotoxicity and hepatotoxicity by chrysin in Wistar rats. Toxicol Mech Methods 2013; 23:337-45.
27. Ayla S, Seckin I, Tanriverdi G, Cengiz M, Eser M, Soner BC, et al. Doxorubicin induced nephrotoxicity: protective effect of nicotinamide. Int J Cell Biol 2011; 2011:390238.
28. Kose E, Beytur A, Dogan Z, Ekincioglu Z, Vardi N, Cinar K, et al. The effects of montelukast against amikacin-induced acute renal damage. Eur Rev Med Pharmacol Sci 2012; 16, 503-511.
29. Tugtepe H, Sener G, Cetinel S, Velioglu-Ogunc A, Yegen BC. Oxidative renal damage in pyelonephritic rats is ameliorated by montelukast, selective leukotriene CysLT1 receptor antagonist. Eur J Pharmacol. 2007; 14;557:69-75.