Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Comparison of In Vivo Nephrotoxicity in the Rabbit by a Pyrrolidinyl-Thio Carbapenem CW-270031

  • Kim, Jong-Myung (Department of Microbiology, Kyungpook National University) ;
  • Ha, Jong-Ryul (Central Research Institute, ChoongWae Pharmaceutical Co. Ltd.) ;
  • Oh, Se-Woong (Central Research Institute, ChoongWae Pharmaceutical Co. Ltd.) ;
  • Kim, Hong-Gi (Central Research Institute, ChoongWae Pharmaceutical Co. Ltd.) ;
  • Lee, Jin-Man (Department of Food and Biotechnology, Hoseo University) ;
  • Kim, Byung-Oh (Department of Applied Biology, Sangju National University) ;
  • Lee, Dong-Gun (Department of Microbiology, Kyungpook National University) ;
  • Lee, Sang-Han (Department of Food Science and Biotechnology, Kyungpook National University) ;
  • Kim, Jong-Guk (Department of Microbiology, Kyungpook National University)
  • Published : 2008.11.30
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Abstract

CW-270031 is a novel synthesized carbapenem antibiotic with a broad antimicrobial activity. Carbapenem antibiotics are well known for their nephrotoxicity. In this study, we evaluated the nephrotoxicity potential of this compound in rabbits, which are known for being more sensitive than other animals to renal insult. CW-270031 was administered to NZW male rabbits via an ear vein (200 mg/kg, single injection). Blood samples were collected on 2, 3, and 4 days after treatment. Urea nitrogen and creatinine in plasma were quantified. Four days after the treatment, all animals were autopsied and histopathological examinations were performed on their kidneys, revealing that cephaloridine and imipenem were highly nephrotoxic, and cefazolin had mild renal toxicity, whereas CW-270031 as well as meropenem and tienam had no toxicity to the kidney. The present findings suggest that CW-270031 is a potential carbapenem antibiotic with no nephrotoxicity.

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References

  1. Balfour, J. A., M. B. Harriet, and N. B. Rex. 1996. Imipenem/cilastatin; An update of its antibacterial activity, pharmacokinetics and therapeutic efficacy in the treatment of serious infections. Drugs 51: 99-136 https://doi.org/10.2165/00003495-199651010-00008
  2. Birnbaum, J., M. Frederick, M. A. Kahan, K. Helmut, and S. M. James. 1985. Carbapenems, a new class of beta-lactam antibiotics. Am. J. Med. 78(Suppl 6A): 3-10
  3. Boyd, J. F., B. T. Butcher, and G. T. Stewart. 1971. The nephrotoxicity and histology of cephaloridine and its polymers in rats. Br. J. Exp. Pathol. 52: 503-509
  4. Bruce, M. T. 1974. Renal tubular transport and nephrotoxicity of beta lactam antibiotics: Structure-activity relationships. Miner. Electrolyte Metab. 20: 221-231
  5. Dean, S. W. 1999. Environmental enrichment of laboratory animals used in regulatory toxicology studies. Lab. Anim. 33: 309-327 https://doi.org/10.1258/002367799780487823
  6. Helmut, K., G. S. Jon, H. Richard, and M. K. Frederick. 1982. Metabolism of thienamycin and related carbapenem antibiotics by the renal dipeptidase, dehydropeptidase-I. Antimicrob. Agents Chemother. 22: 62-70 https://doi.org/10.1128/AAC.22.1.62
  7. Hwang, Y. K., J. S. Chun, P. D. Yoo, J. Y. Ma, B. H. Hyun, S. U. Kim, K. T. Chang, and S. H. Lee. 2004. Occlusal reduction of unilateral molars influences change of stress-related hormones in rats. Scand. J. Lab. Anim. Sci. 31: 73-77
  8. Kahan, F. M., H. Kropp, and J. G. Sundelof. 1983. Thienamycin; development of imipenem-cilastatin. J. Antimicrob. Chemother. 12(Suppl D): 1-35 https://doi.org/10.1093/jac/12.1.1
  9. Kahan, J. S., F. M Kahan, R. Goegelman, S. A. Currie, M. Jackson, E. O. Stapley, et al. 1979. Thienamycin, a new betalactam antibiotic. I. Discovery, taxonomy, isolation and physical properties. J. Antibiot. 32: 1-12 https://doi.org/10.7164/antibiotics.32.1
  10. Kim, J. M., S. W. Oh, J. R. Ha, H. G. Kim, J. M. Lee, B. O. Kim, S. H. Lee, and J. G. Kim. 2006. Antimicrobial effect of novel pyrrollidinyl-thio carbapenem, CW-270031. Kor. J. Microbiol. Biotechnol. 34: 352-356
  11. Kim, J. M., D. W. Lee, Y. S. Song, S. W. Kang, and S. W. Kim. 2007. The within-host population dynamics of normal flora in the presence of an invading pathogen and antibiotic treatments. J. Microbiol. Biotechnol. 16: 331-348
  12. Lee, K. W., H. S. Joo, Y. H. Yang, E. J. Song, and B. G. Kim. 2006. Proteomics for Streptomyces: Industrial proteomics for antibiotics. J. Microbiol. Biotechnol. 16: 331-348
  13. Masatomo, F., S. Yoshihiro, T. H. Eiko, T. Tomoharu, T. Hiroshi, K. Tsuneo, O. Takao, M. Haruki, and S. Makoto. 1992. Stability of meropenem and effect of 1 $\beta$-methyl substitution on its stability in the presence of renal dehydropeptidase I. Antimicrob. Agents Chemother. 36: 1577-1579 https://doi.org/10.1128/AAC.36.7.1577
  14. Petersen, P. J., N. V. Jacobus, W. J. Weiss, and R. T. Testa. 1990. In vitro and in vivo activities of LJC10,627, a new carbapenem with stability to dehydropeptidase I. Antimicrob. Agents Chemother. 35: 203-209
  15. Shishido, H., H. Nagai, A. Kurashima, K. Sato, and K. Kawakami. 1992. A study on in vitro antibacterial activity and clinical usefulness in respiratory tract infections of panipenem/ betamipron, a newly synthesized carbapenem antibiotic. Jpn. J. Antibiot. 45: 143-154
  16. Silverblatt, F., M. Turck, and R. Bulger. 1970. Nephrotoxicity due to cephaloridine: A light- and electron-microscopic study in rabbits. J. Infec. Dis. 122: 33-39 https://doi.org/10.1093/infdis/122.1-2.33
  17. Yang, Y. Y., X. Q. Zhao, Y. Y. Jin, J. H. Huh, J. H. Cheng, D. Singh, H. J. Kwon, and J. W. Suh. 2006. Novel function of cytokinin: A signaling molecule for promotion of antibiotic production in Streptomycetes. J. Microbiol. Biotechnol. 16: 896-900
  18. Zhao, X. Q., Y. Y. Jin, H. J. Kwon, Y. Y. Yang, and J. W. Suh. 2006. S-Adenosylmethionine (SAM) regulates antibiotic biosynthesis in Streptomyces spp. in a mode independent of its role as a methyl donor. J. Microbiol. Biotechnol. 16: 927-932

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