Metabolism of [14C]Benzyl Selenocyanate in the F344 Rat

Karam El-Bayoumy, Pramod Upadhyaya, Vandana Date, Ock Soon Sohn, Emerich S. Fiala, Bandaru Reddy

Research output: Contribution to journalArticle

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Abstract

Benzyl selenocyanate (BSC), a synthetic organoselenium compound, has been shown to inhibit chemically induced tumors in several animal model systems. However, it is not known whether BSC or one of its metabolites is responsible for the chemopreventive effect. An initial approach to this question requires the structural elucidation of BSC metabolites in vitro and in vivo. To determine the structures of BSC metabolites in vitro, we studied the metabolism of [14C]BSC using Aroclor-induced rat liver 9000g supernatant. Under these conditions, BSC was partially converted to dibenzyl diselenide (DDS) and phenylmethaneseleninic acid. The metabolism of [14C]BSC (12.5 mg/kg body weight, 8 mCi/mmol, oral administration) in male F344 rats was also studied. Excretion was monitored by measurement of radioactivity as well as by selenium content using atomic absorption spectrophotometry (AAS). The results indicate that urine was the major route of excretion. Approximately 22% of the dose was excreted in the urine over the course of 35 days; however, a large portion (~70%) of the dose remained in the body. Benzoic acid, hippuric acid, and their sulfate and glucuronide conjugates, accounting for 16% of the dose, were identified in the urine. The formation of these metabolites indicates that BSC is metabolized in part via bond cleavage between the benzyl moiety and the selenocyanate function. Additional support for this cleavage was obtained from fecal analysis; over the course of 23 days 9% of the selenium (AAS) but only <1% of the radioactivity was recovered in feces. No radioactivity was detected in the exhaled air. We also studied the metabolism of [14C]DDS (17.3 mg/kg body weight, 2.5 mCi/mmol) in male F344 rats. Urine was the major route of excretion; 40% of the dose was excreted in urine over the course of 18 days, and <3% was excreted in the feces. As in the case of BSC, a major portion of the dose remained in the body. Benzoic acid and hippuric acid were also identified in the urine. These results suggest that BSC may be converted partially to DDS. The facile reactions in vitro of BSC with numerous proteins and amino acids containing SH, SeMe, or SeSe groups and the relatively slow excretion pattern in vivo compared to inorganic selenium compounds suggest the possible formation of protein adducts which may degrade slowly to yield BSC metabolites. The structures and the biological significance of these protein adducts will be established in future studies.

Original languageEnglish (US)
Pages (from-to)560-565
Number of pages6
JournalChemical research in toxicology
Volume4
Issue number5
DOIs
StatePublished - Sep 1 1991

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Inbred F344 Rats
Metabolism
Rats
Metabolites
Urine
Radioactivity
Benzoic Acid
Atomic Spectrophotometry
Spectrophotometry
Selenium
Feces
benzyl selenocyanate
Organoselenium Compounds
Aroclors
Selenium Compounds
Body Weight
Proteins
Glucuronides
Liver
Sulfates

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

El-Bayoumy, K., Upadhyaya, P., Date, V., Sohn, O. S., Fiala, E. S., & Reddy, B. (1991). Metabolism of [14C]Benzyl Selenocyanate in the F344 Rat. Chemical research in toxicology, 4(5), 560-565. https://doi.org/10.1021/tx00023a012
El-Bayoumy, Karam ; Upadhyaya, Pramod ; Date, Vandana ; Sohn, Ock Soon ; Fiala, Emerich S. ; Reddy, Bandaru. / Metabolism of [14C]Benzyl Selenocyanate in the F344 Rat. In: Chemical research in toxicology. 1991 ; Vol. 4, No. 5. pp. 560-565.
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abstract = "Benzyl selenocyanate (BSC), a synthetic organoselenium compound, has been shown to inhibit chemically induced tumors in several animal model systems. However, it is not known whether BSC or one of its metabolites is responsible for the chemopreventive effect. An initial approach to this question requires the structural elucidation of BSC metabolites in vitro and in vivo. To determine the structures of BSC metabolites in vitro, we studied the metabolism of [14C]BSC using Aroclor-induced rat liver 9000g supernatant. Under these conditions, BSC was partially converted to dibenzyl diselenide (DDS) and phenylmethaneseleninic acid. The metabolism of [14C]BSC (12.5 mg/kg body weight, 8 mCi/mmol, oral administration) in male F344 rats was also studied. Excretion was monitored by measurement of radioactivity as well as by selenium content using atomic absorption spectrophotometry (AAS). The results indicate that urine was the major route of excretion. Approximately 22{\%} of the dose was excreted in the urine over the course of 35 days; however, a large portion (~70{\%}) of the dose remained in the body. Benzoic acid, hippuric acid, and their sulfate and glucuronide conjugates, accounting for 16{\%} of the dose, were identified in the urine. The formation of these metabolites indicates that BSC is metabolized in part via bond cleavage between the benzyl moiety and the selenocyanate function. Additional support for this cleavage was obtained from fecal analysis; over the course of 23 days 9{\%} of the selenium (AAS) but only <1{\%} of the radioactivity was recovered in feces. No radioactivity was detected in the exhaled air. We also studied the metabolism of [14C]DDS (17.3 mg/kg body weight, 2.5 mCi/mmol) in male F344 rats. Urine was the major route of excretion; 40{\%} of the dose was excreted in urine over the course of 18 days, and <3{\%} was excreted in the feces. As in the case of BSC, a major portion of the dose remained in the body. Benzoic acid and hippuric acid were also identified in the urine. These results suggest that BSC may be converted partially to DDS. The facile reactions in vitro of BSC with numerous proteins and amino acids containing SH, SeMe, or SeSe groups and the relatively slow excretion pattern in vivo compared to inorganic selenium compounds suggest the possible formation of protein adducts which may degrade slowly to yield BSC metabolites. The structures and the biological significance of these protein adducts will be established in future studies.",
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El-Bayoumy, K, Upadhyaya, P, Date, V, Sohn, OS, Fiala, ES & Reddy, B 1991, 'Metabolism of [14C]Benzyl Selenocyanate in the F344 Rat', Chemical research in toxicology, vol. 4, no. 5, pp. 560-565. https://doi.org/10.1021/tx00023a012

Metabolism of [14C]Benzyl Selenocyanate in the F344 Rat. / El-Bayoumy, Karam; Upadhyaya, Pramod; Date, Vandana; Sohn, Ock Soon; Fiala, Emerich S.; Reddy, Bandaru.

In: Chemical research in toxicology, Vol. 4, No. 5, 01.09.1991, p. 560-565.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Metabolism of [14C]Benzyl Selenocyanate in the F344 Rat

AU - El-Bayoumy, Karam

AU - Upadhyaya, Pramod

AU - Date, Vandana

AU - Sohn, Ock Soon

AU - Fiala, Emerich S.

AU - Reddy, Bandaru

PY - 1991/9/1

Y1 - 1991/9/1

N2 - Benzyl selenocyanate (BSC), a synthetic organoselenium compound, has been shown to inhibit chemically induced tumors in several animal model systems. However, it is not known whether BSC or one of its metabolites is responsible for the chemopreventive effect. An initial approach to this question requires the structural elucidation of BSC metabolites in vitro and in vivo. To determine the structures of BSC metabolites in vitro, we studied the metabolism of [14C]BSC using Aroclor-induced rat liver 9000g supernatant. Under these conditions, BSC was partially converted to dibenzyl diselenide (DDS) and phenylmethaneseleninic acid. The metabolism of [14C]BSC (12.5 mg/kg body weight, 8 mCi/mmol, oral administration) in male F344 rats was also studied. Excretion was monitored by measurement of radioactivity as well as by selenium content using atomic absorption spectrophotometry (AAS). The results indicate that urine was the major route of excretion. Approximately 22% of the dose was excreted in the urine over the course of 35 days; however, a large portion (~70%) of the dose remained in the body. Benzoic acid, hippuric acid, and their sulfate and glucuronide conjugates, accounting for 16% of the dose, were identified in the urine. The formation of these metabolites indicates that BSC is metabolized in part via bond cleavage between the benzyl moiety and the selenocyanate function. Additional support for this cleavage was obtained from fecal analysis; over the course of 23 days 9% of the selenium (AAS) but only <1% of the radioactivity was recovered in feces. No radioactivity was detected in the exhaled air. We also studied the metabolism of [14C]DDS (17.3 mg/kg body weight, 2.5 mCi/mmol) in male F344 rats. Urine was the major route of excretion; 40% of the dose was excreted in urine over the course of 18 days, and <3% was excreted in the feces. As in the case of BSC, a major portion of the dose remained in the body. Benzoic acid and hippuric acid were also identified in the urine. These results suggest that BSC may be converted partially to DDS. The facile reactions in vitro of BSC with numerous proteins and amino acids containing SH, SeMe, or SeSe groups and the relatively slow excretion pattern in vivo compared to inorganic selenium compounds suggest the possible formation of protein adducts which may degrade slowly to yield BSC metabolites. The structures and the biological significance of these protein adducts will be established in future studies.

AB - Benzyl selenocyanate (BSC), a synthetic organoselenium compound, has been shown to inhibit chemically induced tumors in several animal model systems. However, it is not known whether BSC or one of its metabolites is responsible for the chemopreventive effect. An initial approach to this question requires the structural elucidation of BSC metabolites in vitro and in vivo. To determine the structures of BSC metabolites in vitro, we studied the metabolism of [14C]BSC using Aroclor-induced rat liver 9000g supernatant. Under these conditions, BSC was partially converted to dibenzyl diselenide (DDS) and phenylmethaneseleninic acid. The metabolism of [14C]BSC (12.5 mg/kg body weight, 8 mCi/mmol, oral administration) in male F344 rats was also studied. Excretion was monitored by measurement of radioactivity as well as by selenium content using atomic absorption spectrophotometry (AAS). The results indicate that urine was the major route of excretion. Approximately 22% of the dose was excreted in the urine over the course of 35 days; however, a large portion (~70%) of the dose remained in the body. Benzoic acid, hippuric acid, and their sulfate and glucuronide conjugates, accounting for 16% of the dose, were identified in the urine. The formation of these metabolites indicates that BSC is metabolized in part via bond cleavage between the benzyl moiety and the selenocyanate function. Additional support for this cleavage was obtained from fecal analysis; over the course of 23 days 9% of the selenium (AAS) but only <1% of the radioactivity was recovered in feces. No radioactivity was detected in the exhaled air. We also studied the metabolism of [14C]DDS (17.3 mg/kg body weight, 2.5 mCi/mmol) in male F344 rats. Urine was the major route of excretion; 40% of the dose was excreted in urine over the course of 18 days, and <3% was excreted in the feces. As in the case of BSC, a major portion of the dose remained in the body. Benzoic acid and hippuric acid were also identified in the urine. These results suggest that BSC may be converted partially to DDS. The facile reactions in vitro of BSC with numerous proteins and amino acids containing SH, SeMe, or SeSe groups and the relatively slow excretion pattern in vivo compared to inorganic selenium compounds suggest the possible formation of protein adducts which may degrade slowly to yield BSC metabolites. The structures and the biological significance of these protein adducts will be established in future studies.

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