This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by El Mouedden, M.
Right arrow Articles by Tulkens, P. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by El Mouedden, M.
Right arrow Articles by Tulkens, P. M.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2000, p. 665-675, Vol. 44, No. 3
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Apoptosis in Renal Proximal Tubules of Rats Treated with Low Doses of Aminoglycosides

Mohammed El Mouedden,1 Guy Laurent,2 Marie-Paule Mingeot-Leclercq,1 Henryk S. Taper,3 Jean Cumps,4 and Paul M. Tulkens1,*

Unités de Pharmacologie Cellulaire et Moléculaire,1 de Pharmacocinétique, Métabolisme, Nutrition et Toxicologie,3 et de Chimie Pharmaceutique et Radiopharmacie,4 Université Catholique de Louvain, B-1200 Brussels, and Service d'Histologie et de Cytologie Expérimentale, Université de Mons-Hainaut, B-7000 Mons,2 Belgium

Received 19 August 1999/Returned for modification 1 December 1999/Accepted 20 December 1999

Kidney cortex apoptosis was studied with female Wistar rats treated for 10 days with gentamicin and netilmicin at daily doses of 10 or 20 mg/kg of body weight and amikacin or isepamicin at daily doses of 40 mg/kg. Apoptosis was detected and quantitated using cytological (methyl green-pyronine) and immunohistochemical (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) staining, in parallel with a measurement of drug-induced phospholipidosis (cortical phospholipids and phospholipiduria), cortical proliferative response (3H incorporation in DNA and histoautoradiography after in vivo pulse-labeling with [3H]thymidine), and kidney dysfunction (blood urea nitrogen and creatinine). Gentamicin induced in proximal tubules a marked apoptotic reaction which (i) was detectable after 4 days of treatment but was most conspicuous after 10 days, (ii) was dose dependent, (iii) occurred in the absence of necrosis, and (iv) was nonlinearly correlated with the proliferative response (tubular and peritubular cells). Comparative studies revealed a parallelism among the extents of phospholipidosis, apoptosis, and proliferative response for three aminoglycosides (gentamicin >> amikacin congruent  isepamicin). By contrast, netilmicin induced a marked phospholipidosis but a moderate apoptosis and proliferative response. We conclude that rats treated with gentamicin develop an apoptotic process as part of the various cortical alterations induced by this antibiotic at low doses. Netilmicin, and still more amikacin and isepamicin, appears safer in this respect. Whereas a relation between aminoglycoside-induced tubular apoptosis and cortical proliferative response seems to be established, no simple correlation with phospholipidosis can be drawn.

* Corresponding author. Mailing address: Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, UCL 73.70 Avenue E. Mounier 73, B-1200 Brussels, Belgium. Phone: 32-2-764.73.75. Fax: 32-2-764.73.73. E-mail: elmouedden{at}facm.ucl.ac.be.

Antimicrobial Agents and Chemotherapy, March 2000, p. 665-675, Vol. 44, No. 3
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Chen, H.-H., Sue, Y.-M., Chen, C.-H., Hsu, Y.-H., Hou, C.-C., Cheng, C.-Y., Lin, S.-L., Tsai, W.-L., Chen, T.-W., Chen, T.-H. (2009). Peroxisome proliferator-activated receptor alpha plays a crucial role in L-carnitine anti-apoptosis effect in renal tubular cells. Nephrol Dial Transplant 24: 3042-3049 [Abstract] [Full Text]  
  • Sue, Y.-M., Cheng, C.-F., Chang, C.-C., Chou, Y., Chen, C.-H., Juan, S.-H. (2009). Antioxidation and anti-inflammation by haem oxygenase-1 contribute to protection by tetramethylpyrazine against gentamicin-induced apoptosis in murine renal tubular cells. Nephrol Dial Transplant 24: 769-777 [Abstract] [Full Text]  
  • Denamur, S., Van Bambeke, F., Mingeot-Leclercq, M.-P., Tulkens, P. M. (2008). Apoptosis Induced by Aminoglycosides in LLC-PK1 Cells: Comparative Study of Neomycin, Gentamicin, Amikacin, and Isepamicin Using Electroporation. Antimicrob. Agents Chemother. 52: 2236-2238 [Abstract] [Full Text]  
  • Juan, S.-H., Chen, C.-H., Hsu, Y.-H., Hou, C.-C., Chen, T.-H., Lin, H., Chu, Y.-L., Sue, Y.-M. (2007). Tetramethylpyrazine protects rat renal tubular cell apoptosis induced by gentamicin. Nephrol Dial Transplant 22: 732-739 [Abstract] [Full Text]  
  • Servais, H., Jossin, Y., Van Bambeke, F., Tulkens, P. M., Mingeot-Leclercq, M.-P. (2006). Gentamicin Causes Apoptosis at Low Concentrations in Renal LLC-PK1 Cells Subjected to Electroporation.. Antimicrob. Agents Chemother. 50: 1213-1221 [Abstract] [Full Text]  
  • Bledsoe, G., Crickman, S., Mao, J., Xia, C.-F., Murakami, H., Chao, L., Chao, J. (2006). Kallikrein/kinin protects against gentamicin-induced nephrotoxicity by inhibition of inflammation and apoptosis. Nephrol Dial Transplant 21: 624-633 [Abstract] [Full Text]  
  • Ward, D. T., Maldonado-Perez, D., Hollins, L., Riccardi, D. (2005). Aminoglycosides Induce Acute Cell Signaling and Chronic Cell Death in Renal Cells that Express the Calcium-Sensing Receptor. J. Am. Soc. Nephrol. 16: 1236-1244 [Abstract] [Full Text]  
  • Van Bambeke, F., Michot, J.-M., Tulkens, P. M. (2003). Antibiotic efflux pumps in eukaryotic cells: occurrence and impact on antibiotic cellular pharmacokinetics, pharmacodynamics and toxicodynamics. J Antimicrob Chemother 51: 1067-1077 [Full Text]  
  • Ward, D. T., McLarnon, S. J., Riccardi, D. (2002). Aminoglycosides Increase Intracellular Calcium Levels and ERK Activity in Proximal Tubular OK Cells Expressing the Extracellular Calcium-Sensing Receptor. J. Am. Soc. Nephrol. 13: 1481-1489 [Abstract] [Full Text]  
  • El Mouedden, M., Laurent, G., Mingeot-Leclercq, M.-P., Tulkens, P. M. (2000). Gentamicin-Induced Apoptosis in Renal Cell Lines and Embryonic Rat Fibroblasts. Toxicol Sci 56: 229-239 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»