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Publication Detail

Title: Influence of sevoflurane on the metabolism and renal effects of compound A in rats.

Authors: Kharasch, Evan D; Schroeder, Jesara L; Sheffels, Pam; Liggitt, H Denny

Published In Anesthesiology, (2005 Dec)

Abstract: 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.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.Sevoflurane coadministration with compound A inhibited compound A defluorination while increasing relative metabolism through pathways of sulfoxidation and beta-lyase-catalyzed metabolism, which mediate toxicity. Sevoflurane coadministration 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.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.

PubMed ID: 16306730 Exiting the NIEHS site

MeSH Terms: Anesthetics, Inhalation/pharmacology*; Animals; Biotransformation; Ethers/metabolism*; Ethers/toxicity*; Ethers/urine; Hydrocarbons, Fluorinated/metabolism*; Hydrocarbons, Fluorinated/toxicity*; Hydrocarbons, Fluorinated/urine; Kidney Diseases/chemically induced; Kidney Diseases/pathology; Kidney Function Tests; Kidney/drug effects*; Kidney/pathology; Male; Methyl Ethers/pharmacology*; Rats; Rats, Inbred F344; Sevoflurane; Sulfoxides/metabolism

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