Metabolism and Toxicity of Trichloroethylene in Epididymis and Testis

Forkert, Poh‐Gek; Lash, Lawrence H.; Nadeau, Véronique; Tardif, Robert; Simmonds, Andrea C.

doi:10.1006/taap.2002.9421

Cited by 40 publications

(42 citation statements)

References 37 publications

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“…CYP2Е1 induction by ethanol has been suggested to include two stages: a post-transcriptional mechanism for low doses and a transcriptional mechanism for high doses (31). Our results may have proven that chronically administered ethanol induces CYP2Е1 expression not only in the liver [as was previously described in a number of reviews (35,(37)(38)(39)], but also in the testes, possibly through each of the abovementioned mechanisms. The increase in CYP2E1 mRNA content from our experiment suggests a transcriptional regulation of its expression, or mRNA stabilization.…”

Section: Discussionsupporting

confidence: 80%

“…Lipid peroxidation is a key factor in damaging cell membranes, which means that cytotoxic action could be realized not only by oxygen reactive forms but also by the terminal products of the peroxide catabolism. Testis CYP2Е1 is localized in the Leydig cells, where testosterone biosynthesis takes place (36,37). Consequently, these structures and the damage of their microenvironment by free radicals resulting from ethanol biotransformation could be a reason for the decrease in steroidogenesis enzyme activity.…”

Section: Discussionmentioning

confidence: 99%

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CYP2E1 Testis Expression and Alcoholmediated Changes of Rat Spermatogenesis Indices and Type I Collagen

Shayakhmetova

Bondarenko

Коваленко

et al. 2013

Archives of Industrial Hygiene and Toxicology

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This study is a complex investigation of alcohol-mediated changes in CYP2E1 mRNA and protein expression in the testes, as well as spermatogenesis indices and type I collagen amino acid contents, in male rats. Wistar albino male rats were divided into two groups: I -control (intact animals), II -experimental (chronic alcoholism, exposure to a 15 % ethanol aqueous solution during 150 days). The destructive changes in the spermatogenic epithelium were accompanied by a decrease in sperm number and motility time. CYP2E1 mRNA and protein expression were elevated in the testes 3 and 1.4 times, respectively. Also, signifi cantly lower contents of lysine, glutamic acid, serine, proline, alanine, valine, and phenylalanine residues accompanied by an increase of hydroxyproline, glycine, and threonine residue contents were detected in the skin type I collagen of the experimental group. Chronic ethanol consumption caused testicular failure along with an overexpression of CYP2E1 mRNA and protein in the testes as well as quantitative changes in type I collagen amino acid contents. The profound alcohol-mediated changes in collagen type I amino acid contents may have affected the spermatogenic epithelium state. The modulation of testicular cytochrome P450 2E1 mRNA and protein expression could change the functioning of this isozyme in target organs and take part in the mechanism of ethanol gonadotoxicity.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

CYP2E1 Testis Expression and Alcoholmediated Changes of Rat Spermatogenesis Indices and Type I Collagen

Shayakhmetova

Bondarenko

Коваленко

et al. 2013

Archives of Industrial Hygiene and Toxicology

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“…In our recent studies in mice, we identified the male reproductive system as a sensitive target of TCE-induced toxicity (Forkert et al, 2002). Inhalation exposure to TCE resulted in its metabolism to chloral that was produced at higher levels in the epididymis than in the testis, and is consistent with the greater amounts of CYP2E1 present in the former versus the latter.…”

mentioning

confidence: 67%

“…In addition, CYP2E1 was localized in the epididymal epithelium. To confirm the role of CYP2E1 in TCE metabolism, preincubation of epididymal microsomes with a CYP2E1 inhibitory antibody significantly inhibited the production of chloral from TCE (Forkert et al, 2002). These data correlated with structural damage of the epididymal epithelium, suggesting that generation of CYP2E1-mediated metabolites from TCE plays a role in the toxic response.…”

mentioning

confidence: 97%

Identification of Trichloroethylene and Its Metabolites in Human Seminal Fluid of Workers Exposed to Trichloroethylene

Forkert¹,

Lash²,

Tardif³

et al. 2003

Drug Metab Dispos

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ABSTRACT:We have investigated the potential of the male reproductive tract to accumulate trichloroethylene (TCE) and its metabolites, including chloral, trichloroethanol (TCOH), trichloroacetic acid (TCA), and dichloroacetic acid (DCA). Human seminal fluid and urine samples from eight mechanics diagnosed with clinical infertility and exposed to TCE occupationally were analyzed. In in vivo experimental studies, TCE and its metabolites were determined in epididymis and testis of mice exposed to TCE (1000 ppm) by inhalation for 1 to 4 weeks. In other studies, incubations of monkey epididymal microsomes were performed in the presence of TCE and NADPH. Our results showed that seminal fluid from all eight subjects contained TCE, chloral, and TCOH. DCA was present in samples from two subjects, and only one contained TCA. TCA and/or TCOH were also identified in urine samples from only two subjects. TCE, chloral, and TCOH were detected in murine epididymis after inhalation exposure with TCE for 1 to 4 weeks. Levels of TCE and chloral were similar throughout the entire exposure period. TCOH levels were similar at 1 and 2 weeks but increased significantly after 4 weeks of TCE exposure. Chloral was identified in microsomal incubations with TCE in monkey epididymis. CYP2E1, a P450 that metabolizes TCE, was localized in human and monkey epididymal epithelium and testicular Leydig cells. These results indicated that TCE is metabolized in the reproductive tract of the mouse and monkey. Furthermore, TCE and its metabolites accumulated in seminal fluid, and suggested associations between production of TCE metabolites, reproductive toxicity, and impaired fertility.

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“…Its use has been decreasing in the developed countries, however, it is still used in industrializing countries because of its superior degreasing power, noncombustibility and cheaper cost 1) . TRI is carcinogenic to humans 2) and poses potential adverse effects on the human central nervous system, liver, kidney, and immune system, and also on animal reproductive organs 3,4) . Regarding its influence on the immune system, there are at least two kinds of pathological abnormality: one is generalized hypersensitive dermatitis complicated with severe hepatitis 5,6) , and another is autoimmune hepatitis, which is observed in patients with scleroderma or systemic lupus erythematosus 7,8) .…”

mentioning

confidence: 99%

Sex Differences in Metabolism of Trichloroethylene and Trichloroethanol in Guinea Pigs

Hibino

Wang²,

Naito

et al. 2013

Journal of Occupational Health

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Sex Differences in Metabolism of Trichloroethylene and Trichloroethanol in Guinea Pigs: Yui HIBINO, et al. Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine— Objectives Trichloroethylene (TRI) has the potential to cause generalized dermatitis complicated with hepatitis. The guinea pig maximization test (GPMT) also suggests that both TRI and its metabolite trichloroethanol (TCE) exhibit immunogenicity and possible sex differences in guinea pigs. However, TRI and TCE metabolisms in guinea pigs have not been elucidated in detail. The first issue to clarify may be the sex differences in relation to the immunogenicity. Methods We collected urine from Hartley male and female guinea pigs 24 hours after intracutaneous injection of TRI, TCE or trichloroacetic acid (TCA) during a GPMT and measured the urinary metabolites by gas chromatography‐mass spectrometry. Results After TRI treatment, the amount of TCA was significantly greater in females than males, while there was no sex difference in the total amount (TCA + TCE). TCA was only detected in urine after TCA treatment. Interestingly, not only TCE but also TCA was detected in urine of both sexes after TCE treatment, and the amount of TCA was also greater in females than males. An additional experiment showed that TCE treatment did not result in the detection of urinary TCA in cytochrome P450 (CYP)2E1‐null mice but did in wild‐type mice, suggesting the involvement of CYP2E1 in the metabolism from TCE to TCA. The constitutive expression of CYP2E1 in the liver of guinea pigs was greater in females than males. Conclusions The sex difference in urinary TCA excretion after TRI and TCE treatments may be due to variation of the constitutive expression of CYP2E1.

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Metabolism and Toxicity of Trichloroethylene in Epididymis and Testis

Cited by 40 publications

References 37 publications

CYP2E1 Testis Expression and Alcoholmediated Changes of Rat Spermatogenesis Indices and Type I Collagen

CYP2E1 Testis Expression and Alcoholmediated Changes of Rat Spermatogenesis Indices and Type I Collagen

Identification of Trichloroethylene and Its Metabolites in Human Seminal Fluid of Workers Exposed to Trichloroethylene

Sex Differences in Metabolism of Trichloroethylene and Trichloroethanol in Guinea Pigs

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