Metabolism of [14C]benzyl selenocyanate in the F344 rat

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 (approximately 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential Effects of Selenium on Benign and Malignant Prostate Epithelial Cells: Stimulation of LNCaP Cell Growth by Noncytotoxic, Low Selenite Concentrations

“…There are many reports of experimental evidence that selenium supplementation can reduce the incidence of many types of cancer when nontoxic doses are provided to the diet of rodent species (9,10). Epidemiological studies have identified low selenium levels as one of several factors that are associated with an increased risk of prostate cancer (11,12), but not all studies have shown this relationship (6,13).…”

Potassium bromide or sodium chloride catalyzed acetoxyselenenylation of alkenes with diselenides and mCPBA

“…As shown in Table 2, the reaction was compatible with most of the studied alkenes except bicyclo[2.2.1]hept-2-ene (1j), which provided the corresponding 2-acetoxy-1-selenenylation compounds in good to excellent yields (entries [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. It was also determined that the groups on the benzene ring, no matter whether they were electron-donating or electron-withdrawing groups, did not influence the yield (entries 2-7, 13, 14).…”

“…When treated under the same conditions, the addition to cyclohexene (1i) and 1j proceeded in a trans fashion and the single stereoisomers were isolated with an excellent yield for 3i (entry 9) and a poor yield for 3j due to the steric hinderance effect of the methylene group (entry 10). Compared with 2a, the dibenzyl diselenide (2b), an aliphatic diselenide, also reacted easily with alkenes, but the yields were slightly lower (entries [12][13][14]. From Table 2, it is obvious that the yields for most products 3 were higher when KBr was used as catalyst as opposed to NaCl, so the catalytic effect of KBr is better than NaCl in the acetoxyselenenylation of alkenes.…”

“…In neat AcOH, several kinds of bromide sources were studied. Among them, inorganic bromides usually gave appreciable results and KBr was the most effective while organic bromine compound led to low yield (entries 1, [11][12][13][14][15]. Compared with mCPBA, other oxidants such as Oxone 1 , TBHP, NaBO 3 Á4H 2 O and H 2 O 2 usually resulted in moderate, or poor yields (entries 1, [16][17][18][19].…”

“…Because of their synthetic applications [6] and biological activities such as antitumor, antibacterial activities and other properties [7][8][9][10][11][12][13][14], selenium compounds have been increasing in importance in recent years. The introduction of organolseleno groups into organic molecules has been widely studied, in which the oxyselenenylation reaction is a very useful procedure for the anti-l,2-addition of an organylseleno group and an oxygen substituent (HO, RO, RCO 2 ) to an olefin [15][16][17][18].…”