1 Acta Paulista de Enfermagem Vol: 26(1):. DOI: 10.1590/S0103-21002013000100010

Polimixina B: efeito dose e tempo dependente na nefrotoxicidade in vitro

OBJECTIVE: To characterize the toxicity of polymyxin B (PmxB) in renal cell in different dosage and times.METHODS: LLC-PK1 cells grown in 12 well multiwell plates were divided into the following groups: Control (CTL) - cells maintained in DMEM supplemented with 5%; G1 - cells exposed to concentration of 75µM PmxB G2 - cells exposed to concentration of 375µM PmxB. Each group was assessed at 24,48 and 72 hours as for cell viability (Acridine orange/ethidium bromide) and apoptosis (Hoechst 33342).RESULTS: The data demonstrate the cell viability and apoptosis exposure of three doses of PmxB in three time intervals, with a significant increase in toxicity to high doses and longer duration of stay in the antibiotic to apoptosis.CONCLUSION: Cytotoxicity by PmxB in cell culture model, showed to be time and dose dependent, increasing with increased exposure and higher dose of antibiotic.

  1. Pannu N, Nadim MK. An overview of drug-induced acute kidney injury. Crit Care Med. 36 (4 Suppl):S , 216-23 (2008) .
  2. Hermsen ED, Sulllivan CJ, Rotschafer JC. Polymyxins: pharmacology, pharmacokinectics, pharmacodynamics and clinical applications. Infect Dis Clin North Am. 17(3) , 545-62 (2003) .
  3. Arnold TM, Forrest GN, Messmer KJ. Polymyxin antibiotics for gram-negative infections. Am J HealthSyst Pharm. 64(8) , 819-26 (2007) .
  4. Kwa AL, LimTP, Low JG, Hou J, Kurup A, Prince RA, Tam VH. Phamacokinectics of polymyxin B1 in patients with multidrug resistant Gram-negative bacterial infections. Diagn Microbial Infect Dis. 60(2) , 163-7 (2008) .
  5. Dezoti C, Watanabe M, Pinto CF, Neiva LB, Vattimo MF. Functional protection of heme-oxygenase-1 enzyme in ischemic and toxic acute kidney injury. Acta Paul Enferm. 22 (Especial-Nefrologia) , 490-3 (2009) .
  6. Havasi A, Borkan SC. Apoptosis and acute kidney injury. Kidney Int. 80(1) , 29-40 (2011) .
  7. Coico R. In vitro assays for mouse B and T cell function. Related isolation procedures and functional assays. In: Coligan JE, Kruisbeek AM, Margulies DH, Shevach EM, Strober W, editors.,Current protocols in immunology. Vol. 3.17. New York: John Wiley & Sons, Inc.; p , 1-33 (1995) .
  8. Filatov MV, Varfolomeeva EY. Active dissociation of Hoechst 3from DNA in living mammalian cells. Mutat Res. 1995; 327: 209-15 , 1-2 (3342) .
  9. Falagas ME, Kasiakou SK. Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Crit Care.10(1): R27 , (2006) .
  10. Dollery C, editor. Therapeutic drugs. Edinburgh: Churchill Livingstone; Polymyxin B (sulphate); v. 2, pt. 2 , 151-4 (1991) .
  11. Pedersen RS, Lonka L, Hansen HE. Acute renal failure caused by polymixin B containing ointment. Scand J Urol Nephrol. 21(2) , 153-4 (1987) .
  12. Ouderkirk JP, Nord JA, Turett GS, Kislak JW. Polymyxin B nephrotoxicity and efficancy against nosocomial infections caused by multiresistant gram-negative bacteria. Antimicrob Agents Chemother. 47(8) , 2659-62 (2003) .
  13. Danner RL, Joiner KA, Rubin M, Patterson WH, Johnson N, Ayers KM, et al. Purification, Toxicity, and antiendotoxinactivity of polymyxin B nonapeptide. Antimicrob Agents Chemother. 33(9):.Correspondence to: Maria de Fátima Fernandes VattimoDoctor Enéas Carvalho de Aguiar Avenue, nº 419, Cerqueira César Zip Code: 05403-000 - São Paulo, SP, BrazilEmail: nephron@usp.br Submitted April 19, 2012Accepted February 21, 2013 Conflicts of interest: there are no conflicts of interest to be declared , 1428-34 (1989) .