Protective effect of aminoguanidine against nephrotoxicity induced by amikacin in rats.
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.
Department of Pharmacology, Faculty of Medicine, Inonu University, 44069, Malatya, Turkey. hparlakpinar@inonu.edu.tr
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Parlakpinar
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Koc
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Polat
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Vardi
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Ozer
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Turkoz
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Acet
D000583:Amikacin / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000473:pathology* / Q000517:prevention & control*; D007677:Kidney Function Tests; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D011336:Probability; D020011:Protective Agents / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity
D006146:Guanidines; D020011:Protective Agents; D008315:Malondialdehyde; D000583:Amikacin; C004479:pimagedine