Determination of the sulphoxides and sulphones of three simple sulphides in rat urine: effects of phenobarbitone, beta-naphthoflavone and methimazole.
In this investigation, the measurement and identification of the S-oxidation products of three simple sulphides-ethyl methyl sulphide (EMS), 4-chlorophenyl methyl sulphide (CPMS) and diphenyl sulphide (DPS)-in rat urine were carried out and a study of the effects of phenobarbitone (PB), beta-naphtho flavone (betaNF) and methimazole on the urinary levels of their metabolites was conducted. Male Wistar rats (n = 4) were pretreated with PB (80 mg/kg/day in saline, i.p.), betaNF (100 mg/kg/day in corn oil, i.p.), methimazole (50 mg/kg/day in saline, i.p.) or the vehicles alone (1 mL/kg) for three consecutive days. After pretreatment, EMS, CPMS or DPS (50 mg/kg in corn oil, 500 microL) was administered orally to the appropriate groups of rats. The animals were placed in metabolic cages and urine samples collected at 24 h intervals over 96 h. Chromatographic and spectroscopic techniques were used for the measurement and identification of the sulphoxides and sulphones of EMS, CPMS and DPS in rat urine. Although only a trace of ethyl methyl sulphoxide (EMSO) was present in rat urine after administration of EMS, ethyl methyl sulphone (EMSO(2)) accounted for about 16% of the administered dose in the urine of male rats given EMS. In addition, pretreatment of rats with methimazole significantly decreased the S-oxidation of EMS. 4-Chlorophenyl methyl sulphone (CPMSO(2)) was the main metabolite recovered in the urine of male rats treated with CPMS, accounting for about 10% of the dose. Pretreatment of rats with PB before administration of CPMS significantly increased the levels of CPMSO(2) excreted in the urine. Additionally, pretreatment of rats with methimazole significantly decreased the S-oxidation of CPMS in vivo. About 2.5% of diphenyl sulphoxide (DPSO) and 4% of diphenyl sulphone (DPSO(2)) were recovered in the urine of male rats given DPS. Pretreatment of rats with PB, betaNF or methimazole before administration of DPS decreased the levels of DPSO and DPSO(2) excreted in the urine, although this was not statistically significant. These results indicate that microsomal monooxygenases mediate the S-oxidation of EMS, CPMS and DPS to their corresponding sulphones via a transient sulphoxide in rats.
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N Broad Street, Philadelphia, PA 19140, USA. ivo.nnane@temple.edu
Ivo P
IP
Nnane
Lyaquat A
LA
Damani
D000818:Animals; D002722:Chlorobenzenes / Q000378:metabolism; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D008713:Methimazole / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000378:metabolism*; D013450:Sulfones / Q000652:urine*; D013454:Sulfoxides / Q000652:urine*; D019324:beta-Naphthoflavone / Q000494:pharmacology*
D002722:Chlorobenzenes; D013440:Sulfides; D013450:Sulfones; D013454:Sulfoxides; C403226:ethylmethyl sulfide; C037534:4-chlorophenyl methyl sulfide; D008713:Methimazole; D019324:beta-Naphthoflavone; C444009:diphenyl sulfide; D006899:Mixed Function Oxygenases; D010634:Phenobarbital