Histopathological Changes of the Effect of Ketotifen in a Rat Model of Nephropathy


Ketotifen, Acute kidney injury, glycerol, histopathological.

How to Cite

Shaza Anwar Al Laham. (2019). Histopathological Changes of the Effect of Ketotifen in a Rat Model of Nephropathy . Journal of Pharmacy and Nutrition Sciences, 9(2), 130–135. https://doi.org/10.29169/1927-5951.2019.09.02.13


Acute kidney injury (AKI) remains a common clinical problem with serious consequences and unsatisfactory therapeutic options. Mast cells are distributed in the kidneys, have a role in the inflammation. Thus, a model of Acute kidney injury of rhabdomyolysis induced by glycerol was done in order to investigate the possible healing effect of Ketotifen, a selective stabilizer of mast cells and a histamine H1 receptor antagonist, in rats.

Methods: Wister rats (250-350 g) were used. Renal failure was produced by rats deprived of water for 24 hours followed by i.m. injection with 50% (vol/vol) glycerol (10 ml/kg of body weight). After 30 min, Ketotifen was used at a dose of 2 mg/kg. Rats received treatment for 5 consecutive days. On the 6th day, the rats were sacrificed; blood was obtained for blood urea and creatinine assays. The kidney tissue was used for the determination the histological injury.

Results: The levels of urea and creatinine were decreased significantly (



Korrapati MC, Shaner BE, Schnellmann RG. Recovery from glycerol-induced acute kidney injury is accelerated by suramin. J Pharmacol Exp 2012; 341(1): 126-36. https://doi.org/10.1124/jpet.111.190249

Wang Y-d, Zhang L, Cai G-Y, Zhang X-G, Lv Y, Hong Q, et al. Fasudil ameliorates rhabdomyolysis-induced acute kidney injury via inhibition of apoptosis. Renal Failure 2011; 33(8): 811-8. https://doi.org/10.3109/0886022X.2011.601830

Panizo N, Rubio-Navarro A, Amaro-Villalobos JM, Egido J, Moreno JA. Molecular mechanisms and novel therapeutic approaches to rhabdomyolysis-induced acute kidney injury. Kidney Blood Press Res 2015; 40(5): 520-32. https://doi.org/10.1159/000368528

Komada T, Usui F, Kawashima A, Kimura H, Karasawa T, Inoue Y, et al. Role of NLRP3 inflammasomes for rhabdomyolysis-induced acute kidney injury Scientific Reports 2015; 5: 10901. https://doi.org/10.1038/srep10901

Tong F, Luo L, Liu D. Effect of intervention in mast cell function before reperfusion on renal ischemia-reperfusion injury in rats. Kidney Blood Press Res 2016; 41(3): 335-44. https://doi.org/10.1159/000443437

Heyman SN, Karmeli F, Brezis M, Rachmilewitz D. The effect of ketotifen on nitric oxide synthase activity. BJP 1997; 120(8): 1545-51. https://doi.org/10.1038/sj.bjp.0701063

Eliakim R, Karmeli F, Okon E, Rachmilewitz D. Ketotifen effectively prevents mucosal damage in experimental colitis. Gut 1992; 33(11): 1498-503. https://doi.org/10.1136/gut.33.11.1498

Liu Y, Fu X, Gou L, Li S, Lan N, Zheng Y, et al. L-citrulline protects against glycerol-induced acute renal failure in rats. Renal Failure 2013; 35(3): 367-73. https://doi.org/10.3109/0886022X.2012.760408

Farshid AA, Tamaddonfard E, Belasius MS, Hamzeh-Gooshchi N. Histopathological comparison of the effects of histidine and ketotifen in a rat model of colitis. Bull Vet Inst Pulawy 2009; 53: 795-800.

Erdogan H, Fadillioglu E, Yagmurca M, Uçar M, Irmak MK. Protein oxidation and lipid peroxidation after renal ischemia-reperfusion injury: protective effects of erdosteine and N-acetylcysteine. UROL RES 2006; 34(1): 41-6. https://doi.org/10.1007/s00240-005-0031-3

Park CH, Tanaka T, Cho EJ, Park JC, Shibahara N, Yokozawa T. Glycerol-induced renal damage improved by 7-O-galloyl-D-sedoheptulose treatment through attenuating oxidative stress. Biol Pharm Bull 2012; 35(1): 34-41. https://doi.org/10.1248/bpb.35.34

Singh AP, Muthuraman A, Jaggi AS, Singh N, Grover K, Dhawan R. Animal models of acute renal failure. Pharmacological Reports 2012; 64(1): 31-44. https://doi.org/10.1016/S1734-1140(12)70728-4

Stefanovic V, Savic V, Vlahovic P, Cvetkovic T, Najman S, Mitic-Zlatkovic M. Reversal of experimental myoglobinuric acute renal failure with bioflavonoids from seeds of grape. Renal Failure 2000; 22(3): 255-66. https://doi.org/10.1081/JDI-100100870

Manikandan R, Beulaja M, Thiagarajan R, Pandi M, Arulvasu C, Prabhu NM, et al. Ameliorative effect of ferulic acid against renal injuries mediated by nuclear factor-kappaB during glycerol-induced nephrotoxicity in Wistar rats. Renal Failure 2014; 36(2): 154-65. https://doi.org/10.3109/0886022X.2013.835223

Kalia N, Brown NJ, Wood RF, Pockley AG. Ketotifen abrogates local and systemic consequences of rat intestinal ischemia–reperfusion injury. JGH 2005; 20(7): 1032-8. https://doi.org/10.1111/j.1440-1746.2005.03767.x

Li Z, Wang Y. Effect of NADPH oxidase inhibitor-apocynin on the expression of Src homology-2 domain-containing phosphatase-1 (SHP-1) exposed renal ischemia/reperfusion injury in rats. Toxicology Reports 2015; 2: 1111-6. https://doi.org/10.1016/j.toxrep.2015.07.019

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