Skip to main content
Top
Published in: Urolithiasis 4/2004

01-08-2004 | Original paper

Protective effect of aminoguanidine against nephrotoxicity induced by amikacin in rats

Authors: H. Parlakpinar, M. Koc, A. Polat, N. Vardi, M. K. Ozer, Y. Turkoz, A. Acet

Published in: Urolithiasis | Issue 4/2004

Login to get access

Abstract

Aminoglycoside antibiotics have long been used in antibacterial therapy. Despite their beneficial effects, aminoglycosides have considerable nephrotoxic and ototoxic side effects. It has been reported that reactive oxygen radical species (ROS) play role in the pathophysiology of aminoglycosides-induced nephrotoxicity. Aminoguanidine (AG) is an effective antioxidant and free radical scavenger which has long been known to protect against nephrotoxicity. We investigated the effects of AG on amikacin (AK)-induced changes of renal malondialdehyde (MDA), glutathione (GSH), blood urea nitrogen (BUN), serum creatinine (Cr) and albumin (Alb) which are used to monitor the development of renal tubular damage. Morphological changes in the kidney were also examined using light microscopy. A total of 21 rats were equally divided into three groups which were: (1) injected with saline, (2) injected with AK, and (3) injected with AK+AG, respectively. AK administration to control rats increased renal MDA and decreased GSH levels. AG administration before AK injection caused significant decreases in MDA and increases in GSH levels in kidneys compared to rats treated with AK alone. The serum BUN level increased slightly, Cr and serum Alb did not change as a result of any treatment. AG tended to decrease the level of serum BUN and did not cause any change in Alb or Cr levels. Morphological changes, including glomerular, tubular epithelial alterations and interstitial edema, were clearly observed in AK-treated rats. In addition, AG reversed the morphological damage to the kidney induced by AK. The results show that AG has a protective effect on nephrotoxicity induced by AK and may therefore improve the therapeutic index of AK.
Literature
1.
go back to reference Begg EJ, Barclay ML (1995) Aminoglycosides-50 years on. Br J Clin Pharmacol 39: 597PubMed Begg EJ, Barclay ML (1995) Aminoglycosides-50 years on. Br J Clin Pharmacol 39: 597PubMed
2.
go back to reference Klein J, Koren G, McLeod SM (1992) Comparison methods for prediction of nephrotoxicity during development. Dev Pharmacol Ther 19: 80PubMed Klein J, Koren G, McLeod SM (1992) Comparison methods for prediction of nephrotoxicity during development. Dev Pharmacol Ther 19: 80PubMed
3.
go back to reference Ibrahim S, Langhendries JP, Bernard A, Tulkens PM (1994) Urinary phospholipids excretion in neonates treated with amikacin. Int J Clin Pharmacol Res 14: 149PubMed Ibrahim S, Langhendries JP, Bernard A, Tulkens PM (1994) Urinary phospholipids excretion in neonates treated with amikacin. Int J Clin Pharmacol Res 14: 149PubMed
4.
go back to reference Baliga R, Zhang Z, Baliga M, Ueda N, Shah SV (1998) In vitro and in vivo evidence suggesting a role for iron in cisplatin-induced nephrotoxicity. Kidney Int 53: 394CrossRefPubMed Baliga R, Zhang Z, Baliga M, Ueda N, Shah SV (1998) In vitro and in vivo evidence suggesting a role for iron in cisplatin-induced nephrotoxicity. Kidney Int 53: 394CrossRefPubMed
5.
go back to reference Rao M, Kumar MM, Rao MA (1999) In vitro and in vivo effects of phenolic antioxidants against cisplatin-induced nephrotoxicity. J Biochem 125: 383PubMed Rao M, Kumar MM, Rao MA (1999) In vitro and in vivo effects of phenolic antioxidants against cisplatin-induced nephrotoxicity. J Biochem 125: 383PubMed
6.
go back to reference Misko TP, Moore WM, Kasten TP, Nickols GA, Corbett JA, Tilton RG, McDaniel ML, Williamson JR, Currie MG (1993) Selective inhibition of the inducible nitric oxide synthase by aminoguanidine. Eur J Pharmacol 233: 119CrossRefPubMed Misko TP, Moore WM, Kasten TP, Nickols GA, Corbett JA, Tilton RG, McDaniel ML, Williamson JR, Currie MG (1993) Selective inhibition of the inducible nitric oxide synthase by aminoguanidine. Eur J Pharmacol 233: 119CrossRefPubMed
7.
go back to reference Tilton RG, Chang K, Hasan KS, Smith SR, Petrash JM, Misko TP, Moore WM, Currie MG, Corbett JA, McDaniel ML (1993) Prevention of diabetic vascular dysfunction by guanidines. Inhibition of nitric oxide synthase versus advanced glycation endproduct formation. Diabetes 42: 221PubMed Tilton RG, Chang K, Hasan KS, Smith SR, Petrash JM, Misko TP, Moore WM, Currie MG, Corbett JA, McDaniel ML (1993) Prevention of diabetic vascular dysfunction by guanidines. Inhibition of nitric oxide synthase versus advanced glycation endproduct formation. Diabetes 42: 221PubMed
8.
go back to reference Sugimoto K, Yagihashi S (1997) Effects of aminoguanidine on structural alterations of microvessels in peripheral nerve of streptozotocin diabetic rats. Microvasc Res 53: 105CrossRefPubMed Sugimoto K, Yagihashi S (1997) Effects of aminoguanidine on structural alterations of microvessels in peripheral nerve of streptozotocin diabetic rats. Microvasc Res 53: 105CrossRefPubMed
9.
go back to reference Ihm SH, Yoo HJ, Park SW, Ihm J (1999) Effect of aminoguanidine on lipid peroxidation in streptozotocin induced diabetic rats. Metabolism 48: 1141PubMed Ihm SH, Yoo HJ, Park SW, Ihm J (1999) Effect of aminoguanidine on lipid peroxidation in streptozotocin induced diabetic rats. Metabolism 48: 1141PubMed
10.
go back to reference Szabo C, Ferrer-Sueta G, Zingarelli B, Southan GJ, Salzman AL, Radi R (1997) Mercaptoethylguanidine and guanidine inhibitors of nitric-oxide synthase react with peroxynitrite and protect against peroxynitrite-induced oxidative damage. J Biol Chem 272: 9030CrossRefPubMed Szabo C, Ferrer-Sueta G, Zingarelli B, Southan GJ, Salzman AL, Radi R (1997) Mercaptoethylguanidine and guanidine inhibitors of nitric-oxide synthase react with peroxynitrite and protect against peroxynitrite-induced oxidative damage. J Biol Chem 272: 9030CrossRefPubMed
11.
go back to reference Aoki K, Ohmori M, Takimoto M, Ota H, Yoshida T (1997) Cocaine-induced liver injury in mice is mediated by nitric oxide and reactive oxygen species. Eur J Pharmacol 336: 43CrossRefPubMed Aoki K, Ohmori M, Takimoto M, Ota H, Yoshida T (1997) Cocaine-induced liver injury in mice is mediated by nitric oxide and reactive oxygen species. Eur J Pharmacol 336: 43CrossRefPubMed
12.
go back to reference Shiomi M, Wakabayashi Y, Sano T, Sinoda Y, Nimura Y, Ishimura Y, Suematsu M (1998) Nitric oxide suppression reversibly attenuates mitochondrial dysfunction and cholestasis in endotoxemic rat liver. Hepatology 27: 108PubMed Shiomi M, Wakabayashi Y, Sano T, Sinoda Y, Nimura Y, Ishimura Y, Suematsu M (1998) Nitric oxide suppression reversibly attenuates mitochondrial dysfunction and cholestasis in endotoxemic rat liver. Hepatology 27: 108PubMed
13.
go back to reference Al-Shabanah OA, Alam KS, Nagi MN, Al-Rikabi AC, Al-Bekairi AM (2000) Protective effect of aminoguanidine, a nitric oxide synthase inhibitor, against carbon tetrachloride induced hepatotoxicity in mice. Life Sci 66: 265CrossRefPubMed Al-Shabanah OA, Alam KS, Nagi MN, Al-Rikabi AC, Al-Bekairi AM (2000) Protective effect of aminoguanidine, a nitric oxide synthase inhibitor, against carbon tetrachloride induced hepatotoxicity in mice. Life Sci 66: 265CrossRefPubMed
14.
go back to reference Mansour MA, Mostafa AM, Nagi MN, Khattab MM, Al-Shabnah OA (2002) Protective effect of aminoguanidine against nephrotoxicity induced by cisplatin in normal rats. Comp Biochem Physiol C 132: 123CrossRef Mansour MA, Mostafa AM, Nagi MN, Khattab MM, Al-Shabnah OA (2002) Protective effect of aminoguanidine against nephrotoxicity induced by cisplatin in normal rats. Comp Biochem Physiol C 132: 123CrossRef
15.
go back to reference Parlakpinar H, Ozer MK, Sahna E, Vardi N, Cigremis Y, Acet A (2003) Amikacin-induced acute renal injury in rats protective role of melatonin. J Pineal Res 35: 85CrossRefPubMed Parlakpinar H, Ozer MK, Sahna E, Vardi N, Cigremis Y, Acet A (2003) Amikacin-induced acute renal injury in rats protective role of melatonin. J Pineal Res 35: 85CrossRefPubMed
16.
go back to reference Takizawa S, Fukuyama N, Hirabayashi H, Nakazawa H, Shinohara Y (1999) Dynamics of nitrotyrosine formation and decay in rat brain during focal ischemia-reperfusion J Cereb Blood Flow Metab 19: 667 Takizawa S, Fukuyama N, Hirabayashi H, Nakazawa H, Shinohara Y (1999) Dynamics of nitrotyrosine formation and decay in rat brain during focal ischemia-reperfusion J Cereb Blood Flow Metab 19: 667
17.
go back to reference Vermeulen NPE, Baldew GS (1992) The role of lipid peroxidation in the nephrotoxicity of cisplatin. Biochem Pharmacol 44: 1193CrossRefPubMed Vermeulen NPE, Baldew GS (1992) The role of lipid peroxidation in the nephrotoxicity of cisplatin. Biochem Pharmacol 44: 1193CrossRefPubMed
18.
go back to reference Sahna E, Parlakpinar H, Ozturk F, Cigremis Y, Acet A (2003) The protective effects of physiological and pharmacological concentrations of melatonin on renal ischemia-reperfusion injury in rats. Urol Res 31: 188CrossRefPubMed Sahna E, Parlakpinar H, Ozturk F, Cigremis Y, Acet A (2003) The protective effects of physiological and pharmacological concentrations of melatonin on renal ischemia-reperfusion injury in rats. Urol Res 31: 188CrossRefPubMed
20.
go back to reference Moore RD, Lietman PS, Smith C (1987). Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis 155: 93PubMed Moore RD, Lietman PS, Smith C (1987). Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis 155: 93PubMed
21.
go back to reference Prins JM, Weverling GJ, De Blok K, Van Ketel RJ, Speelman P (1996) Validation and nephrotoxicity of a simplified once-daily aminoglycoside schedule and guidelines for monitoring therapy. Antimicrob Agents Chemother 40: 2494PubMed Prins JM, Weverling GJ, De Blok K, Van Ketel RJ, Speelman P (1996) Validation and nephrotoxicity of a simplified once-daily aminoglycoside schedule and guidelines for monitoring therapy. Antimicrob Agents Chemother 40: 2494PubMed
22.
go back to reference Smith CR, Lipsky JJ, Laskin OL, Hellman DB, Mellits ED, Longstreth J, Lietman PS (1980) Double-blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin. N Engl J Med 302: 1106PubMed Smith CR, Lipsky JJ, Laskin OL, Hellman DB, Mellits ED, Longstreth J, Lietman PS (1980) Double-blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin. N Engl J Med 302: 1106PubMed
23.
go back to reference Gilbert DN (1995) Aminoglycosides. Principles and practice of infectious diseases, 4th edn. Churchill Livingstone, New York, p 279 Gilbert DN (1995) Aminoglycosides. Principles and practice of infectious diseases, 4th edn. Churchill Livingstone, New York, p 279
24.
go back to reference Hagiwara M, Inagaki M, Kanamura K, Ohta H, Hidaka H (1988) Inhibitory effects of aminoglycosides on renal protein phosphorylation by protein kinase C. J Pharmacol Exp Ther 244: 355PubMed Hagiwara M, Inagaki M, Kanamura K, Ohta H, Hidaka H (1988) Inhibitory effects of aminoglycosides on renal protein phosphorylation by protein kinase C. J Pharmacol Exp Ther 244: 355PubMed
25.
go back to reference Halliwell B, Gutteridge JMC, Cross CE (1992) Free radicals, antioxidants and human disease. Where are we now? J Lab Clin Med 119: 598PubMed Halliwell B, Gutteridge JMC, Cross CE (1992) Free radicals, antioxidants and human disease. Where are we now? J Lab Clin Med 119: 598PubMed
26.
go back to reference Wolff SP (1993) Diabetes mellitus and free radicals. Free radicals, transition metals and oxidative stressing the etiology of diabetes mellitus and complications. Br Med Bull 49: 642PubMed Wolff SP (1993) Diabetes mellitus and free radicals. Free radicals, transition metals and oxidative stressing the etiology of diabetes mellitus and complications. Br Med Bull 49: 642PubMed
27.
go back to reference Yildiz G, Demiryurek AT, Sahin-Erdemli I, Kanzik I (1998) Comparison of antioxidant activities of aminoguanidine, methyl-guanidine and guanidine by luminol-enhanced chemiluminescence. Br J Pharmacol 124: 905PubMed Yildiz G, Demiryurek AT, Sahin-Erdemli I, Kanzik I (1998) Comparison of antioxidant activities of aminoguanidine, methyl-guanidine and guanidine by luminol-enhanced chemiluminescence. Br J Pharmacol 124: 905PubMed
28.
go back to reference Giardino I, Fard AK, Hatchell DL, Brownlee M (1998) Aminoguanidine inhibits reactive oxygen species formation, lipid peroxidation, and oxidant-induced apoptosis. Diabetes 47: 1114PubMed Giardino I, Fard AK, Hatchell DL, Brownlee M (1998) Aminoguanidine inhibits reactive oxygen species formation, lipid peroxidation, and oxidant-induced apoptosis. Diabetes 47: 1114PubMed
29.
go back to reference Babu E, Gopalakrishnan VK, Sriganth IN, Gopalakrishnan R, Sakthisekaran D (1995) Cisplatin induced nephrotoxicity and the modulating effect of glutathione ester. Mol Cell Biochem 144: 7PubMed Babu E, Gopalakrishnan VK, Sriganth IN, Gopalakrishnan R, Sakthisekaran D (1995) Cisplatin induced nephrotoxicity and the modulating effect of glutathione ester. Mol Cell Biochem 144: 7PubMed
30.
go back to reference Parlakpinar H, Sahna E, Ozer MK, Ozugurlu F, Vardi N, Acet A (2002) Physiological and pharmacological concentrations of melatonin protect against cisplatin induced acute renal injury. J Pineal Res 33: 161CrossRefPubMed Parlakpinar H, Sahna E, Ozer MK, Ozugurlu F, Vardi N, Acet A (2002) Physiological and pharmacological concentrations of melatonin protect against cisplatin induced acute renal injury. J Pineal Res 33: 161CrossRefPubMed
31.
go back to reference Sugimoto H, Shikata K, Wada J, Horiuchi S, Makino H (1999) Advanced glycation end products–cytokine–nitric oxide sequence pathway in the development of diabetic nephropathy: aminoguanidine ameliorates the overexpression of tumor necrosis factor-alpha and inducible nitric oxide synthase in diabetic rat glomeruli. Diabetologia 42: 878CrossRefPubMed Sugimoto H, Shikata K, Wada J, Horiuchi S, Makino H (1999) Advanced glycation end products–cytokine–nitric oxide sequence pathway in the development of diabetic nephropathy: aminoguanidine ameliorates the overexpression of tumor necrosis factor-alpha and inducible nitric oxide synthase in diabetic rat glomeruli. Diabetologia 42: 878CrossRefPubMed
Metadata
Title
Protective effect of aminoguanidine against nephrotoxicity induced by amikacin in rats
Authors
H. Parlakpinar
M. Koc
A. Polat
N. Vardi
M. K. Ozer
Y. Turkoz
A. Acet
Publication date
01-08-2004
Publisher
Springer-Verlag
Published in
Urolithiasis / Issue 4/2004
Print ISSN: 2194-7228
Electronic ISSN: 2194-7236
DOI
https://doi.org/10.1007/s00240-004-0399-5

Other articles of this Issue 4/2004

Urolithiasis 4/2004 Go to the issue