Alterações Renais por Aminoglicosídeos

 

Vanessa Barboza de Souza, Rodrigo Fagundes de Oliveira, Aurigena Ferreira, Raimundo de Araújo Júnior

Departamento de Morfologia, Universidade Federal do Rio Grande do Norte, Brasil

 

O objetivo dessa revisão é o acesso crítico à literatura a respeito dos efeitos tóxicos dos aminoglicosídeos nas estruturas histológicas do rim. Foram pesquisados os artigos científicos nas bases de dados da ScienceDirect, cujas palavras-chaves foram “NEPHROTOXICITY”, “AMINOGLYCOSIDES”, “GENTAMICIN” e “RENAL INJURY”. Os artigos que apresentavam apenas o abstract disponível, bem como as revisões sistemáticas foram excluídos. Foram considerados somente artigos relacionados com a morfologia do sistema renal publicados em língua inglesa e espanhola, e aqueles acessados através da base de dados da Capes. Dois revisores independentes avaliaram a elegibilidade e a qualidade metodológica de cada ensaio experimental e extraíram os dados. Sete foram selecionados. As variáveis estudadas foram as seguintes: autor(es), ano, objetivo, metodologia e conclusões. Os artigos selecionados utilizaram desde técnicas histoquímica e imunoistoquímica para identificação morfológica das alterações renais até espectroscopia. Foi possível também, verificar métodos de prevenção à nefrotoxicidade induzida pelos aminoglicosídeos, minimizando efeitos tóxicos. Os achados histopatológicos mostraram que a administração de aminoglicosídeos causaram apoptose e edema celular, interrupção da membrana basal, redução do espaço de Bowman e necrose tubular aguda.

Palavras-chave: aminoglicosídeos; apoptose; gentamicina; necrose tubular aguda.

 

Kidney Alterations by Aminoglycosides

The purpose of the review is to critically assess the published literature regarding the toxic effect of aminoglycosides in kidney morphological structures. Scientific manuscripts had been evaluated by the ScienceDirect databases whose keywords were “NEPHROTOXICITY”, “AMINOGLYCOSIDES”, “GENTAMICIN” e “RENAL INJURY”. The articles that presented only available abstract, as well as the systematic reviews were removed. Articles related with morphology of the renal system published in English and Spanish language, and those had assess through the database of the Capes had been considered only. Two independent reviewers assessed the eligibility, and the methodological quality of each trial, and extracted the data. Seven studies were included on this review. The studied variables were the following ones: author, age, objective, methodology and conclusions. The selected articles used since histochemical and immunoistochemical techniques for morphological identification of the kidney alterations until spectroscopy. It was possible also, to verify methods of prevention to the induced nephrotoxicity for the aminoglycosides, being minimized toxic effect. The histopathological findings showed that administration of aminoglycosides caused apoptosis and intracellular edema, basement membrane interruption, glomeruli narrowing of the Bowman’s space and acute tubule necrosis.

Key-words: aminoglycosides; apoptosis; gentamicin; acute tubular necrosis.

 

 

Texto completo disponível apenas em PDF.

Full text only available in PDF format.

 

 

REFERÊNCIAS

1 -Souza LB, Pinto LP, MedeirosAMC,Araújo Jr RF, Mesquita OJX . Oralmanifestationsin HIV-infected patientsin a Brazilian population. Pesqui Odontol Bras 2000;14:15-29.

        [ Links ]

2 -Kierszenbaum AL. Sistema urinário. In: KierszenbaumAL, organizador. Histologia e biologia celular: uma introdução à patologia. Rio de Janeiro: Elsevier; 2004. p.389-15.

3 -Bennett CC. The aminoglycosides. Primary Care Update for OB/GYNS 1996;6:186-91.

4 -Busse HJ, Wostmann C, Bakker EP. The bactericidalaction of streptomycin: membrane permeabilization caused by the insertion of mistranslated proteins into the cytoplasmic membrane of Escherichia coli and subsequent caging of the antibiotic inside the cells due to degradation of these proteins. J Gen Microbiol 1992;138:551-61.

5 -Chambers, HF. Aminoglicosídeos. In: Brunton, Larence L, Lazo JS, Parker KL, organizadores. Goodman E. Gilman. As bases farmacológicas de terapêutica. 10 ed. Rio de Janeiro: McGraw-Hill 2006;1039-54.

6 -Martínez-Salgado C, Henández-López FJ, Novoa-López JM. Glomerular nephrotoxicity of aminoglycosides. Toxicol Appl Pharmacol 2007;223:86-98.

7 -Bowman RL, Silverblatt FJ, Kaloyanides GJ. Comparison of the nephrotoxicity of netilmicin and gentamicin in rats. Antimicrob Agents Chemother 1977;12:474-8.

8 -French MA, Cerra FB, Plaut ME, Schentag JJ. Amikacin and nephrotoxicityin criticallyillpatients.AntimicrobAgents Chemother 1981;19:147-52.

9 -Hanslik T, Blanchet F, Noohy D, Pirotzy E, Guilmard C, Seta N, et al. Effect of the platelet activatin factor antagonist BN52021 in rabbits: Role in gentamicin nephrotoxicity. Toxicol Appl Pharmacol 1994;128:111-5.

10 -GurnaniK, KhouriH, Couture M, Bergeron MG, Beauchamp D, Carrier D. Molecular basis os theinhibition of gentamicin nephrotoxicity by daptomycin; an infrared spectroscopic investigation. Biochim Biophys Acta 1995;1237:86-94.

11 - Takamoto K, Kawada M, Usui T, Ishizuka M, Ikeda D. Aminoglycosides antibiotics reduce glucose reabsorptionin kidney through dow-regulation of SGLT1. Biochem Biophys Res Commun. 2003;308:866-71.

12 -Watanabe A, Nagai J, Adachi Y, Katsube T, Kitahara Y, Murakami T, et al. Targeted prevention of renal accumulation and toxicity of gentamicin by aminoglycoside binding receptor antagonists. J Control Release 2004;95:423-33.

13 -Hosaka EM, Santos OFP, Seguro AC, Vattimo MFF. Effect of cyclooxygenase inhibitors on gentamicin induced nephrotoxicity in rats. Braz J Med Biol Res 2004;37:979-85.

14 -Yanagida C, Ito K, Komiya I, Horie T. Protective effect of fosfomycin on gentamicin-induced lipid peroxidation of rat renal tissue. Chem Biol Interact 2004;148:139-47.

15 -Servais H, Smissen PVD, Thirion G, Essen GVD, Bambeke FV,Tulkens PM, Mingeot-Leclercq M-P. Gentamicin-induced apoptosisin LLC-PK1 cells: Involvement oflysossomes and mitochondria. Toxicol Appl Pharmacol 2005;206:321-33.

16 -Polat A, Palakpinar H, Tasdemir S, Colak C, Vardi N, Ucar M, Emre MH, Acet A. Protective role of aminoguanidine on gentamicin-induced acute renal failure in rats. Acta Histochem 2006;108:365-71.

17 -Allory Y, Commo F, Boccon-Gibod L, Sibony M, Callard P, Ronco P, et al. Sulfated HNK1 epitope in developing and mature kidney: a new marker for thin ascending loop of Henle and tubular injury in acute tubular necrosis. J Histochem Cytochem 2006;54:575-84.

 

 

Correspondência:

Prof. Dr. Raimundo de Araújo Júnior

Departamento de Morfologia

Centro de Biociências

Universidade Federal do Rio Grande do Norte

Av. Senador Salgado Filho, S/N

Campus Universitário

Lagoa Nova

59072-970 Natal, RN, Brasil

e-mail: araujojr@cb.ufrn.br