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 Zhao, Y. L.
Right arrow Articles by Hasegawa, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhao, Y. L.
Right arrow Articles by Hasegawa, T.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 2002, p. 1522-1528, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1522-1528.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Shiga-Like Toxin II Derived from Escherichia coli O157:H7 Modifies Renal Handling of Levofloxacin in Rats

Ying Lan Zhao,1,2 Xiao Bo Cen,2 Masafumi Ito,3 Keiko Yokoyama,4 Kenji Takagi,1 Kiyoyuki Kitaichi,1 Masayuki Nadai,5 Michio Ohta,4 Kenzo Takagi,1 and Takaaki Hasegawa1*

Department of Medical Technology, Nagoya University School of Health Sciences,1 Department of Pathology,3 Department of Bacteriology, Nagoya University School of Medicine,4 Faculty of Pharmacy, Meijo University, Nagoya, Japan,5 National Safety Assessment Center of Traditional Chinese Medicine, First University Hospital, Sichuan University, Chengdu, China2

Received 9 April 2001/ Returned for modification 26 September 2001/ Accepted 31 January 2002

The effect of Shiga-like toxin II (SLT-II) (2 µg/animal), which was derived from Escherichia coli O157:H7, on renal handling of levofloxacin (LVX), a model drug for quinolone antimicrobial agents, was investigated in rats 24 h after intravenous injection. In histopathological examination, acute tubular injury was observed in SLT-II-treated rats, but the glomeruli were not injured. SLT-II significantly increased the steady-state concentration of LVX in plasma to 1.5-fold that of control rats. SLT-II induced significant decreases in the glomerular filtration rate (GFR) and renal clearance (CLR) of LVX. SLT-II slightly, but significantly, increased the unbound fraction and decreased renal plasma flow with no change in the extraction ratio of p-aminohippurate. SLT-II significantly increased concentrations of tumor necrosis factor alpha (TNF-{alpha}) and nitrite and nitrate (NOx) in plasma. The TNF-{alpha} inhibitor pentoxifylline partly, but significantly, inhibited SLT-II-induced decreases in the GFR and CLR of LVX; in contrast, S-methylisothiourea, a selective inhibitor of inducible nitric oxide synthase, did not. Western blotting analysis revealed that SLT-II did not alter the levels of multidrug resistance-associated protein 2 (Mrp2) and P-glycoprotein in kidneys 24 h after injection, assuming the lack of involvement of Mrp2 and P-glycoprotein in SLT-II-induced acute renal tubular injury and renal handling of LVX observed 24 h after SLT-II injection. The present study suggests that SLT-II impairs the renal handling of LVX by decreasing GFR and causing decreased renal plasma flow.

* Corresponding author. Mailing address: Department of Medical Technology, Nagoya University School of Health Sciences, 1-1-20 Daikominami, Higashi-ku, Nagoya 461-8673, Japan. Phone: 81-52-719-3008. Fax: 81-52-719-3009. E-mail: hasegawa{at}met.nagoya-u.ac.jp.

Antimicrobial Agents and Chemotherapy, May 2002, p. 1522-1528, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1522-1528.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Okuda, T., Tokuda, N., Numata, S.-i., Ito, M., Ohta, M., Kawamura, K., Wiels, J., Urano, T., Tajima, O., Furukawa, K., Furukawa, K. (2006). Targeted Disruption of Gb3/CD77 Synthase Gene Resulted in the Complete Deletion of Globo-series Glycosphingolipids and Loss of Sensitivity to Verotoxins. J. Biol. Chem. 281: 10230-10235 [Abstract] [Full Text]  
  • Sugie, M., Asakura, E., Zhao, Y. L., Torita, S., Nadai, M., Baba, K., Kitaichi, K., Takagi, K., Takagi, K., Hasegawa, T. (2004). Possible Involvement of the Drug Transporters P Glycoprotein and Multidrug Resistance-Associated Protein Mrp2 in Disposition of Azithromycin. Antimicrob. Agents Chemother. 48: 809-814 [Abstract] [Full Text]  
  • Hidemura, K., Zhao, Y. L., Ito, K., Nakao, A., Tatsumi, Y., Kanazawa, H., Takagi, K., Ohta, M., Hasegawa, T. (2003). Shiga-Like Toxin II Impairs Hepatobiliary Transport of Doxorubicin in Rats by Down-Regulation of Hepatic P Glycoprotein and Multidrug Resistance-Associated Protein Mrp2. Antimicrob. Agents Chemother. 47: 1636-1642 [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»