Tributyltin is metabolized by cytochrome P-450 (CYP) system enzymes, and its metabolic fate may contribute to the toxicity of the chemical. In the present study, it is examined whether sex differences in the metabolism of tributyltin exist in rats. In addition, the in vivo and in vitro metabolism of tributyltin was investigated using rat hepatic CYP systems to confirm the principal CYP involved. A significant sex difference in metabolism occurred both in vivo and in vitro, suggesting that one of the CYPs responsible for tributyltin metabolism in rats is male specific or predominant at least. Eight cDNA-expressed rat CYPs, including typical phenobarbital (PB)-inducible forms and members of the CYP2C subfamily, were tested to determine their capability for tributyltin metabolism. Among the enzymes studied, a statistically significant dealkylation of tributyltin was mediated by CYP2C6 and 2C11. Furthermore, the sex difference in metabolism disappeared in vitro after anti-rat CYP2C11 antibody pretreatment because CYP2C11 is a major male-specific form in rats. These results indicate that CYP2C6 is the principal CYP for tributyltin metabolism in female rats, whereas CYP2C11 as well as 2C6 is involved in tributyltin metabolism in male rats, and it is suggested that CYP2C11 is responsible for the significant sex difference in the metabolism of tributyltin observed in rats.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.taap.2005.06.013 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Endocrine Disruptors Chemicals: Impacts of Bisphenol A, Tributyltin and Lead on Thyroid Function.
Mol Cell Endocrinol
January 2025
Programa de Pós-graduação em Medicina (Endocrinologia), Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro-RJ, Brazil; Centro de Pesquisa em Medicina de Precisão, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro-RJ, Brazil; Programa de Pós-graduação em Ciências Biológicas (Fisiologia), Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro-RJ, Brazil.
The large-scale industrial production characteristic of the last century led to an increase in man-made compounds and mobilization of natural compounds, many of which can accumulate in the environment and organisms due to their bioaccumulation and biomagnification properties. The endocrine system is especially vulnerable to these compounds that are known as endocrine disruptor chemicals (EDCs). Thyroid hormones (THs) are essential for normal development and growth, besides being the main regulators of basal metabolic rate.
View Article and Find Full Text PDFAdipose tissue as target of environmental toxicants: focus on mitochondrial dysfunction and oxidative inflammation in metabolic dysfunction-associated steatotic liver disease.
Mol Cell Biochem
December 2024
Department of Surgery I-Clinic of Surgical Semiotics & Thoracic Surgery, Center for Hepato-Biliary and Pancreatic Surgery, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Eftimie Murgu Sq., No.2, 300041, Timișoara, Romania.
Obesity, diabetes, and their cardiovascular and hepatic comorbidities are alarming public health issues of the twenty-first century, which share mitochondrial dysfunction, oxidative stress, and chronic inflammation as common pathophysiological mechanisms. An increasing body of evidence links the combined exposure to multiple environmental toxicants with the occurrence and severity of metabolic diseases. Endocrine disruptors (EDs) are ubiquitous chemicals or mixtures with persistent deleterious effects on the living organisms beyond the endocrine system impairment; in particular, those known as metabolism-disrupting chemicals (MDCs), increase the risk of the metabolic pathologies in adult organism or its progeny.
View Article and Find Full Text PDFDelineating lipidomic landscapes in human and mouse ovaries: Spatial signatures and chemically-induced alterations via MALDI mass spectrometry imaging: Spatial ovarian lipidomics.
Environ Int
December 2024
Department of Pathology, University of Illinois Chicago, Chicago, IL, USA; Chicago Center for Health and Environment, University of Illinois Chicago, Chicago, IL, USA. Electronic address:
This study addresses the critical gap in understanding the ovarian lipidome's abundance, distribution, and vulnerability to environmental disruptors, a largely unexplored field. Leveraging the capabilities of matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI), we embarked on a novel exploration of the ovarian lipidome in both mouse and human healthy tissues. Our findings revealed that the obesogenic chemical tributyltin (TBT), at environmentally relevant exposures, exerts a profound and region-specific impact on the mouse ovarian lipidome.
View Article and Find Full Text PDFTranscriptomic and epigenomic signatures distinguish high- and low-risk endotypes for liver tumor development.
Environ Mol Mutagen
November 2024
Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, Texas, USA.
The epigenome is a target for environmental exposures and a potential determinant of inter-individual differences in response. In genetically identical C57Bl/6 mice exposed from gestation to weaning to the endocrine-disrupting chemical (EDC) tributyltin (TBT), hepatic tumor development later in life varied across multiple cohorts over time and depending on sex and diet. In one cohort where approximately half of TBT-exposed male mice developed liver tumors at 10 months (Katz et al.
View Article and Find Full Text PDFEndocrine-Disrupting Chemicals, Hypothalamic Inflammation and Reproductive Outcomes: A Review of the Literature.
Int J Mol Sci
October 2024
Second Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, 'Aretaieion' University Hospital, 11528 Athens, Greece.
Endocrine-disrupting chemicals (EDCs) are environmental and industrial agents that interfere with hormonal functions. EDC exposure is linked to various endocrine diseases, especially in reproduction, although the mechanisms remain unclear and effects vary among individuals. Neuroinflammation, particularly hypothalamic inflammation, is an emerging research area with implications for endocrine-related diseases like obesity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!