Evaluation of the Effect of Telmisartan on Gentamicin-Induced Nephrotoxicity in Rats


Nephrotoxicity, Gentamicin, Telmisartan, Oxidative Stress, Rat.

How to Cite

Reem Haj Darwish, & Shadi Homs. (2018). Evaluation of the Effect of Telmisartan on Gentamicin-Induced Nephrotoxicity in Rats. Journal of Pharmacy and Nutrition Sciences, 8(2), 76–82. https://doi.org/10.6000/1927-5951.2018.08.02.7


Gentamicin (Gen) is widely used against serious infections, but its therapeutic use is limited due to its nephrotoxicity which causes acute renal failure.
We aimed to evaluate the potential protective effect of highly selective angiotensin II (Ang II) type 1 (AT1) receptor blocker Telmisartan (Tel) on the renal damage generated by Gentamicin in rats.
36 Male Wistar rats were divided into six groups (6 rats each): Naive, Tel group (10 mg/kg/day orally for 7 days), control (1 ml/day 0.9% NaCl intraperitoneally i.p. for 7 days), Gen group (100 mg/kg/day i.p for 7 days), Gen + Tel 5 mg/kg/day concurrently for 7 days, Gen + Tel 10 mg/kg/day concurrently for 7 days.
Concentrations of serum urea, serum creatinine, and renal reduced glutathione (GSH) levels were evaluated after treatment.
Gen was observed to cause a severe nephrotoxicity, which was evidenced by an elevation of serum urea and creatinine levels which weren’t altered by simultaneous treatment with Tel. The oxidative stress caused by Gen demonstrated by a decrease in renal GSH level was significantly attenuated by Telmisartan (the higher dose).
Conclusion: This study proves the nephrotoxicity caused by Gentamicin, and suggests that concurrent treatment with Telmisartan ameliorate oxidative stress induced by gentamicin without changes to serum urea and creatinine.



Lopez-Novoa JM, Quiros Y, Vicente L, Morales AI, Lopez-Hernandez FJ. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney International 2011; 79(1): 33-45. https://doi.org/10.1038/ki.2010.337

Wargo KA, Edwards JD. Aminoglycoside-induced nephrotoxicity. Journal of Pharmacy Practice 2014; 27(6): 573-7. https://doi.org/10.1177/0897190014546836

Ali BH, Al Za'abi M, Blunden G, Nemmar A. Experimental gentamicin nephrotoxicity and agents that modify it: a mini-review of recent research. Basic & Clinical Pharmacology & Toxicology 2011; 109(4): 225-32. https://doi.org/10.1111/j.1742-7843.2011.00728.x

Balakumar P, Rohilla A, Thangathirupathi A. Gentamicin-induced nephrotoxicity: Do we have a promising therapeutic approach to blunt it? Pharmacological Research 2010; 62(3): 179-86. https://doi.org/10.1016/j.phrs.2010.04.004

Koyner JL, Sher Ali R, Murray PT. Antioxidants. Do they have a place in the prevention or therapy of acute kidney injury? Nephron Experimental Nephrology 2008; 109(4): e109-17. https://doi.org/10.1159/000142935

Zorov DB. Amelioration of aminoglycoside nephrotoxicity requires protection of renal mitochondria. Kidney International 2010; 77(10): 841-3. https://doi.org/10.1038/ki.2010.20

McClellan KJ, Markham A. Telmisartan. Drugs 1998; 56(6): 1039-44; discussion 45-6. https://doi.org/10.2165/00003495-199856060-00007

Ladino M, Hernandez Schulman I. Renovascular and renoprotective properties of telmisartan: clinical utility. International Journal of Nephrology and Renovascular Disease 2010; 3: 33-8.

Frampton JE. Telmisartan: a review of its use in cardiovascular disease prevention. Drugs 2011; 71(6): 651-77. https://doi.org/10.2165/11206710-000000000-00000

Battershill AJ, Scott LJ. Telmisartan: a review of its use in the management of hypertension. Drugs 2006; 66(1): 51-83. https://doi.org/10.2165/00003495-200666010-00004

Remuzzi A, Remuzzi G. Potential protective effects of telmisartan on renal function deterioration. Journal of the Renin-Angiotensin-Aldosterone System: JRAAS 2006; 7(4): 185-91. https://doi.org/10.3317/jraas.2006.036

Rang H. Rang and Dale’s Pharmacology, Churchill Livingstone. Elsevier; 2007.

Fouad AA, Qureshi HA, Al-Sultan AI, Yacoubi MT, Al-Melhim WN. Nephroprotective effect of telmisartan in rats with ischemia/reperfusion renal injury. Pharmacology 2010; 85(3): 158-67. https://doi.org/10.1159/000269779

Malik S, Suchal K, Gamad N, Dinda AK, Arya DS, Bhatia J. Telmisartan ameliorates cisplatin-induced nephrotoxicity by inhibiting MAPK mediated inflammation and apoptosis. European Journal of Pharmacology 2015; 748: 54-60. https://doi.org/10.1016/j.ejphar.2014.12.008

Heeba GH. Angiotensin II receptor blocker, losartan, ameliorates gentamicin-induced oxidative stress and nephrotoxicity in rats. Pharmacology 2011; 87(3-4): 232-40. https://doi.org/10.1159/000325457

El-Kashef DH, El-Kenawi AE, Suddek GM, Salem HA. Flavocoxid attenuates gentamicin-induced nephrotoxicity in rats. Naunyn-Schmiedeberg's Archives of Pharmacology 2015; 388(12): 1305-15. https://doi.org/10.1007/s00210-015-1164-8

Rodrigues FA, Prata MM, Oliveira IC, Alves NT, Freitas RE, Monteiro HS, et al. Gingerol fraction from Zingiber officinale protects against gentamicin-induced nephrotoxicity. Anti-microbial Agents and Chemotherapy 2014; 58(4): 1872-8. https://doi.org/10.1128/AAC.02431-13

Duan SB, Wang YH, Liu FY, Xu XQ, Wang P, Zou Q, et al. The protective role of telmisartan against nephrotoxicity induced by X-ray contrast media in rat model. Acta Radiologica 2009; 50(7): 754-9. https://doi.org/10.1080/02841850902995544

Zou R, He Y, Li YQ, Han M, Ma ZF, Liu XC, et al. Telmisartan protects 5/6 Nx rats against renal injury by enhancing nNOS-derived NO generation via regulation of PPARgamma signaling. American Journal of Translational Research 2014; 6(5): 517-27.

Zhang Q, Xiao X, Li M, Li W, Yu M, Zhang H, et al. Telmisartan improves kidney function through inhibition of the oxidative phosphorylation pathway in diabetic rats. Journal of Molecular Endocrinology 2012; 49(1): 35-46. https://doi.org/10.1530/JME-12-0020

Tsunenari I, Ohmura T, Seidler R, Chachin M, Hayashi T, Konomi A, et al. Renoprotective effects of telmisartan in the 5/6 nephrectomised rats. Journal of the Renin-Angiotensin-Aldosterone System: JRAAS 2007; 8(2): 93-100. https://doi.org/10.3317/jraas.2007.017

Servais H, Ortiz A, Devuyst O, Denamur S, Tulkens PM, Mingeot-Leclercq MP. Renal cell apoptosis induced by nephrotoxic drugs: cellular and molecular mechanisms and potential approaches to modulation. Apoptosis: an Interna-tional Journal on Programmed Cell Death 2008; 13(1): 11-32. https://doi.org/10.1007/s10495-007-0151-z

Goodfriend TL, Elliott ME, Catt KJ. Angiotensin receptors and their antagonists. The New England Journal of Medicine 1996; 334(25): 1649-54. https://doi.org/10.1056/NEJM199606203342507

Michel MC, Brunner HR, Foster C, Huo Y. Angiotensin II type 1 receptor antagonists in animal models of vascular, cardiac, metabolic and renal disease. Pharmacology & Therapeutics 2016; 164: 1-81. https://doi.org/10.1016/j.pharmthera.2016.03.019

Sachse A, Wolf G. Angiotensin II-induced reactive oxygen species and the kidney. Journal of the American Society of Nephrology: JASN 2007; 18(9): 2439-46. https://doi.org/10.1681/ASN.2007020149

Kasap B, Turkmen M, Kiray M, Kuralay F, Soylu A, Tugyan K, et al. Effects of pentoxifylline on gentamicin-induced nephrotoxicity. Renal Failure 2013; 35(10): 1376-81. https://doi.org/10.3109/0886022X.2013.828359

Randjelovic P, Veljkovic S, Stojiljkovic N, Velickovic L, Sokolovic D, Stoiljkovic M, et al. Protective effect of selenium on gentamicin-induced oxidative stress and nephrotoxicity in rats. Drug and Chemical Toxicology 2012; 35(2): 141-8. https://doi.org/10.3109/01480545.2011.589446

Randjelovic P, Veljkovic S, Stojiljkovic N, Jankovic-Velickovic L, Sokolovic D, Stoiljkovic M, et al. Salicylic acid attenuates gentamicin-induced nephrotoxicity in rats. The Scientific World Journal 2012; 2012: 390613. https://doi.org/10.1100/2012/390613

Stojiljkovic N, Stoiljkovic M, Mihailovic D, Randjelovic P, Ilic S, Gocmanac-Ignjatovic M, et al. Beneficial effects of calcium oral coadministration in gentamicin-induced nephrotoxicity in rats. Renal Failure 2012; 34(5): 622-7. https://doi.org/10.3109/0886022X.2012.664809

Martinez-Salgado C, Lopez-Hernandez FJ, Lopez-Novoa JM. Glomerular nephrotoxicity of aminoglycosides. Toxicology and Applied Pharmacology 2007; 223(1): 86-98. https://doi.org/10.1016/j.taap.2007.05.004

Wang ZK, Liu ZY, Yu HB. Protective effect of telmisartan on rats with renal failure and its mechanism. Asian Pacific Journal of Tropical Medicine 2015; 8(6): 498-501. https://doi.org/10.1016/j.apjtm.2015.05.007

Nagai J, Takano M. Molecular aspects of renal handling of aminoglycosides and strategies for preventing the nephrotoxicity. Drug Metabolism and Pharmacokinetics 2004; 19(3): 159-70. https://doi.org/10.2133/dmpk.19.159

Benson SC, Pershadsingh HA, Ho CI, Chittiboyina A, Desai P, Pravenec M, et al. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity. Hypertension 2004; 43(5): 993-1002. https://doi.org/10.1161/01.HYP.0000123072.34629.57

Cabezas F, Lagos J, Cespedes C, Vio CP, Bronfman M, Marzolo MP. Megalin/LRP2 expression is induced by peroxisome proliferator-activated receptor -alpha and -gamma: implications for PPARs' roles in renal function. PloS One 2011; 6(2): e16794. https://doi.org/10.1371/journal.pone.0016794

Otunctemur A, Ozbek E, Cekmen M, Cakir SS, Dursun M, Polat EC, et al. Protective effect of montelukast which is cysteinyl-leukotriene receptor antagonist on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. Renal Failure 2013; 35(3): 403-10. https://doi.org/10.3109/0886022X.2012.761040

Patel Manali B, Deshpande S, Shah G. Evaluation of efficacy of vitamin E and N-acetyl cysteine in gentamicin-induced nephrotoxicity in rats. Renal Failure 2011; 33(3): 341-7. https://doi.org/10.3109/0886022X.2011.560987

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