1 |
|
Metabolism of tert-butylhydroquinone to S-substituted conjugates in the male fischer 344 rat
tert-Butyl-4-hydroxyanisole (BHA) and its demethylated analog, tert- butyl-hydroquinone (TBHQ), are antioxidants used in food. Both BHA and TBHQ have been shown to promote kidney and bladder carcinogenesis in the rat. We have previously demonstrated that glutathione (GSH) conjugates of a variety of hydroquinones are nephrotoxic and proposed that GSH conjugation serves to target these compounds to the kidney. In the present study, we examined the metabolism of TBHQ, focusing on the formation of potentially nephrotoxic sulfur-containing metabolites. 2-tert-Butyl-5-glutathion-S-ylhydroquinone, 2- tert-butyl-6-glutathion-S-ylhydroquinone, and 2-tert-butyl-3,6-bisglutathion- S-ylhydroquinone were identified as biliary metabolites of TBHQ (1.0 mmol/kg, ip) in male F344 rats, accounting for 2.2% of the dose. Liquid chromatography/mass spectroscopic analysis of urine also revealed the presence of additional sulfur-containing metabolites, tentatively identified as 2,5-dihydroxy-3-tert-butylthiophenol, 2,5-dihydroxy-4-tert- butylthiophenol, and their S-methyl derivatives. No mercapturic acids of TBHQ were found in the urine. The major biliary and urinary metabolites were TBHQ- glucuronide and TBHQ-sulfate, with a trace of TBHQ excreted unchanged. The results indicate that TBHQ undergoes oxidation and GSH conjugation in vivo in the male F344 rat. These conjugates are excreted into bile and undergo further metabolism prior to excretion in urine. Formation of the S-containing metabolites of TBHQ may occur in amounts sufficient to play a role in the toxicity of TBHQ to kidney and bladder. Chemicals/CAS: 2-tert-butylhydroquinone, 1948-33-0; Antioxidants; Butylated Hydroxyanisole, 25013-16-5; Glutathione, 70-18-8; Hydroquinones; Sulfides
|
[Abstract]
|
2 |
|
Hexachlorobenzene and its metabolites pentachlorophenol and tetrachlorohydroquinone: Interacion with thyroxine binding sites of rat thyroid hormone carriers ex vivo and in vitro
Previous results have indicated that hexachlorobenzene (HCB)-induced hypothyroidism may be caused by its main metabolite pentachlorophenol (PCP), and by tetrachlorohydroquinone (TCHQ), rather than by the parent compound. In the present experiments it was investigated whether hormone displacement from serum carriers could be a factor in the development of this hypothyroidism. In an in vitro competition assay PCP was an effective competitor for the thyroxine (T4)-binding sites of serum carriers, whereas HCB was ineffective. Ex vivo experimental results demonstrated occupation of T4-binding sites in sera from PCP-exposed animals but not in sera from HCB-or TCHQ-treated animals. Competing ability for T4-binding sites was still present in sera of PCP-exposed animals but was absent in HCB- or TCHQ-exposed animals. The results suggest that thyroid hormone displacement by the major metabolite PCP may play a role in HCB-induced hypothyroidism. Chemicals/CAS: 2,3,5,6-tetrachlorohydroquinone, 87-87-6; Hexachlorobenzene, 118-74-1; Hydroquinones; Pentachlorophenol, 87-86-5; Thyroxine, 7488-70-2
|
[Abstract]
|
3 |
|
Lack of clastogenic effects in cultured human lymphocytes treated with hydroquinone
Hydroquinone (HQ) occurs in the environment as a result of manmade processes as well as in natural products from plants and animals. The compound has been reported to produce chromosomal effects in some in vivo and in vitro animal models. However, its potential to produce similar effects in human lymphocytes is less clear. To obtain more information on the clastogenic potential of HQ in human cells, its ability to induce structural chromosomal aberrations in human lymphocytes in vitro has been examined, both in the absence and presence of exogenous metabolic activation. Moreover, the effect of HQ pre-incubation on peroxide induced clastogenicity was studied, because HQ has putative chemopreventive activity as well. It was found that HQ was cytotoxic, but did not induce chromosomal aberrations in human lymphocytes cultured in vitro. Additionally, it was observed that pre-incubation of lymphocytes with HQ resulted in a concentration dependent reduction of the H2O2 induced chromosomal aberrations (P=0.069). However, this effect was present at 12 mM H2O2 only, because of high cytotoxicity at higher dosages. © 2003 Elsevier Ltd. All rights reserved.
|
[Abstract]
|