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Influence of sevoflurane on the metabolism and renal effects of compound a in rats

Publication ,  Journal Article
Kharasch, ED; Schroeder, JL; Sheffels, P; Liggitt, HD
Published in: Anesthesiology
January 1, 2005

Background: The sevoflurane degradation product compound A is nephrotoxic in rats. In contrast, patient exposure to compound A during sevoflurane anesthesia has no clinically significant renal effects. The mechanism for this difference is incompletely understood. One possibility is that the metabolism and toxicity of compound A in humans is prevented by sevoflurane. However, the effect of sevoflurane on compound A metabolism and nephrotoxicity is unknown. Thus, the purpose of this investigation was to determine the effect of sevoflurane on the metabolism and renal toxicity of compound A in rats. Methods: Male rats received 0.25 mmol/kg intraperitoneal compound A, alone and during sevoflurane anesthesia (3%, 1.3 minimum alveolar concentration, for 3 h). Compound A metabolites in urine were quantified, and renal function was evaluated by serum creatinine and urea nitrogen, urine volume, osmolality, protein excretion, and renal tubular histology. Results: Sevoflurane coadministration with compound A inhibited compound A defluorination while increasing relative metabolism through pathways of sulfoxidation and β-lyase-catalyzed metabolism, which mediate toxicity. Sevoflurane co-administration with compound A increased some (serum creatinine and urea nitrogen, and necrosis) but not other (urine volume, osmolality, and protein excretion) indices of renal toxicity. Conclusions: Sevoflurane does not suppress compound A nephrotoxicity in rats in vivo. These results do not suggest that lack of nephrotoxicity in surgical patients exposed to compound A during sevoflurane anesthesia results from an inhibitory effect of sevoflurane on compound A metabolism and toxicity. Rather, these results are consistent with differences between rats and humans in compound A exposure and inherent susceptibility to compound A nephrotoxicity. © 2005 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.

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Published In

Anesthesiology

DOI

EISSN

1528-1175

ISSN

0003-3022

Publication Date

January 1, 2005

Volume

103

Issue

6

Start / End Page

1183 / 1188

Related Subject Headings

  • Anesthesiology
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
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Kharasch, E. D., Schroeder, J. L., Sheffels, P., & Liggitt, H. D. (2005). Influence of sevoflurane on the metabolism and renal effects of compound a in rats. Anesthesiology, 103(6), 1183–1188. https://doi.org/10.1097/00000542-200512000-00012
Kharasch, E. D., J. L. Schroeder, P. Sheffels, and H. D. Liggitt. “Influence of sevoflurane on the metabolism and renal effects of compound a in rats.” Anesthesiology 103, no. 6 (January 1, 2005): 1183–88. https://doi.org/10.1097/00000542-200512000-00012.
Kharasch ED, Schroeder JL, Sheffels P, Liggitt HD. Influence of sevoflurane on the metabolism and renal effects of compound a in rats. Anesthesiology. 2005 Jan 1;103(6):1183–8.
Kharasch, E. D., et al. “Influence of sevoflurane on the metabolism and renal effects of compound a in rats.” Anesthesiology, vol. 103, no. 6, Jan. 2005, pp. 1183–88. Scopus, doi:10.1097/00000542-200512000-00012.
Kharasch ED, Schroeder JL, Sheffels P, Liggitt HD. Influence of sevoflurane on the metabolism and renal effects of compound a in rats. Anesthesiology. 2005 Jan 1;103(6):1183–1188.

Published In

Anesthesiology

DOI

EISSN

1528-1175

ISSN

0003-3022

Publication Date

January 1, 2005

Volume

103

Issue

6

Start / End Page

1183 / 1188

Related Subject Headings

  • Anesthesiology
  • 1103 Clinical Sciences