Inhibition of glutathione-S- aryltransferase from rat liver by organogermanium, lead and tin compounds

Henry, Roy A.; Byington, Keith H.

doi:10.1016/0006-2952(76)90012-5

Cited by 66 publications

(17 citation statements)

References 22 publications

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“…Greater inhibitory e!ectiveness of DBT compared with TBT and TPT is contrary to the general structure}activity and physical property relationships reported for inhibition of glutathione S-transferase activity in "sh (Al-Ghais and Ali, 1999) and rat (Henry and Byington, 1976), induction of mitochondrial swelling and hemolysis (Henry and Byington, 1976), and toxicity caused by organotin compounds (WHO, 1990;Morcillo et al, 1997). These studies on the biochemical mechanism of action and tissue distribution of organotins have revealed high a$nity of these compounds toward amino acids, peptides, and proteins having }SH and " NH groups rather than lipids (Henry and Byington, 1976;Morcillo et al, 1997;Kannan et al, 1997). Though the explanation for distinct patterns of "sh liver carboxylesterase inhibition by dialkyl and trialkyl tins is not known at present, it may be attributed to the possible additional role of the carbohydrate moiety of the glycoprotein molecule of carboxylesterases and/or serine or other amino acids constituting the active site in organotin}enzyme interaction (Hosokawa et al, 1990).…”

Section: Discussionmentioning

confidence: 57%

Differential Inhibition of Xenobiotic-Metabolizing Carboxylesterases by Organotins in Marine Fish

Al-Ghais

Ahmad

Ali

2000

Ecotoxicology and Environmental Safety

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Section: Discussionmentioning

confidence: 57%

Differential Inhibition of Xenobiotic-Metabolizing Carboxylesterases by Organotins in Marine Fish

Al-Ghais

Ahmad

Ali

2000

Ecotoxicology and Environmental Safety

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“…While we did not measure hepatic GST activity nor the proportions of the various types of B a P metabolites accumulated in the bile, the current literature does not support such a mechanism. For instance, the in vitro inhibition of hepatic GST activity by TBT has been reported in fish [26] and in mammals [27]. Thus, TBT has the potential to inhibit, rather than induce, hepatic GST activity.…”

Section: Discussionmentioning

confidence: 99%

Mutual in vivo interactions between benzo[a]pyrene and tributyltin in brook trout (Salvelinus fontinalis)

Padrós

Pelletier

Reader

et al. 2000

Enviro Toxic and Chemistry

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Tributyltin (TBT), an organometal used as an antifouling biocide, has been reported to inhibit cytochrome P450 (P450) 1A isozyme. Benzo[a]pyrene (BaP), a widespread carcinogenic polycyclic aromatic hydrocarbon, is both metabolized and bioac‐tivated to carcinogenic BaP diol‐epoxide (BPDE) metabolites primarily by hepatic P450 1A. Hence, TBT may inhibit the metabolism and bioactivation of BaP This study was therefore designed to examine the potential in vivo interactions between BaP and TBT in a model fish. Male brook trout (Salvelinus fontinalis) were given a single intraperitoneal injection of either BaP (10 mg/kg), TBT (10 mg/kg), or both in combination. After 48 h, blood, bile, and liver samples were collected and analyzed for a suite of biomarkers associated with P450 activity, BaP metabolism and bioactivation, and TBT metabolism. The results showed that TBT significantly (p < 0.05; two‐way analysis of variance) inhibited (a) the induction of hepatic P450 1A‐mediated ethoxyresorufin O‐deethylase (EROD) and P450‐mediated 3‐cyano‐7‐ethoxycoumarin‐O‐deethylase (CN‐ECOD) activities by BaP, (b) the formation of biliary BaP metabolites, and (c) the formation of (+)‐anti‐BPDE‐plasma albumin adducts as measured by high‐performance liquid chromatography/fluorescence. Notably, TBT alone did not inhibit EROD activity but induced CN‐ECOD activity (p < 0.05). Gas chromatography/mass spectrometry analysis indicated that the combined BaP + TBT dose resulted in higher levels of dibutyltin metabolites in the bile (p < 0.05). The present study supports the hypothesis that a single, high dose of TBT can antagonize the metabolism and bioactivation of BaP at least by inhibiting the induction of P4501A. On the other hand, BaP unexpectedly potentiated the metabolism of TBT, suggesting that hepatic isoforms other than P4501A may be responsible for TBT metabolism. Finally, this study supports the utility of a biomarker approach to screen potential xenobiotic interactions in aquatic organisms and to obtain mechanistic insights.

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“…Significant increases in testosterone levels were reported in clams (Ruditapes decussata) exposed to TBT due to inhibition of the P450 aromatase that converts testosterone to estradiol 17-␤ [Morcillo et al, 1998]. Organotins are also potent inhibitors of glutathione transferase-mediated conjugation and excre-tion in mammals and fish [Henry and Byington, 1976;Al-Ghais and Ali, 1999], and this could also be involved in mollusk masculinization [Ronis and Mason, 1996]. Preferential inhibition by TBT of the conjugation/detoxification of AAF metabolites, as compared to 2-AA derivatives, could explain the increased AAF activation in clams exposed to this organotin.…”

Section: Discussionmentioning

confidence: 99%

Mutagenic activation of arylamines by subcellular fractions of Chamaelea gallina clams exposed to environmental pollutants

Rodríguez-Ortega

Rodríguez‐Ariza

Amezcua³

et al. 2003

Environ and Mol Mutagen

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Biochemical measurements in the sentinel clam Chamaelea gallina have been used as biomarkers of marine pollution. In this study, S9, cytosolic fractions (CF), and microsomal fractions (MF) prepared from unexposed clams and clams exposed to model pollutants were used to activate 2-aminoanthracene (2-AA) and 2-acetylaminofluorene (AAF) to mutagens in Salmonella typhimurium strain BA149, which overexpresses O-acetyltransferase. Arylamine activation was similar with subcellular fractions from unexposed and Aroclor 1254-exposed clams, but decreased with fractions from As(III)- and Cu(II)-exposed clams. Bioactivation of arylamines by CF was higher than by MF, and higher with NADH than with NADPH as the reducing agent. alpha-Naphthoflavone inhibited AAF activation by CF and MF, but increased 2-AA activation nearly twofold. In contrast to the results with arylamine activation, benzo[a]pyrene hydroxylase (BPH) activity increased twofold in fractions from Aroclor 1254- and Cu(II)-exposed clams. Activation of 2-AA was also evaluated using S9 fractions from clams sampled at littoral sites with different pollutant levels. Compared to a reference site, lower 2-AA bioactivation and higher BPH activity were found in clams containing high levels of copper and organic contaminants, although the differences were not statistically significant. While these findings agree with the results of the model Cu(II) exposure, the effects of other pollutants cannot be ruled out. The results of the study demonstrate that arylamine activation by clams is not preferentially catalyzed by microsomal monooxygenases but by unknown cytosolic system(s), and that bioactivation of 2-AA and AAF appears to occur by different pathways.

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Inhibition of glutathione-S- aryltransferase from rat liver by organogermanium, lead and tin compounds

Cited by 66 publications

References 22 publications

Differential Inhibition of Xenobiotic-Metabolizing Carboxylesterases by Organotins in Marine Fish

Differential Inhibition of Xenobiotic-Metabolizing Carboxylesterases by Organotins in Marine Fish

Mutual in vivo interactions between benzo[a]pyrene and tributyltin in brook trout (Salvelinus fontinalis)

Mutagenic activation of arylamines by subcellular fractions of Chamaelea gallina clams exposed to environmental pollutants

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