Involvement of constitutive androstane receptor in liver hypertrophy and liver tumor development induced by triazole fungicides

Tamura, Kazutoshi; Inoue, Kaoru; Takahashi, Miwa; Matsuo, Saori; Irie, Kaoru; Kodama, Yukio; Gamo, Toshie; Ozawa, Shogo; Yoshida, Midori

doi:10.1016/j.fct.2015.01.021

Cited by 28 publications

(38 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In previous studies using CARKO mice, eosinophilic proliferating lesions were increased in WT mice only by PB treatment Sakamoto et al, 2013), suggesting that the treatment-related increase in eosinophilic type could indicate the involvement of CAR in hepatotumorigenesis in mice. In addition, eosinophilic foci and/or adenomas were also induced by GBE or cyproconazole; these compounds also cause CAR-mediated liver tumor development (Maeda et al, 2015;Tamura et al, 2015). Basophilic and other proliferating lesions were not changed by treatment with IMA, similar to the results of treatment with PB.…”

Section: Discussionsupporting

confidence: 66%

“…1) was conducted to clarify the involvement of CAR in IMA-inducing liver tumor development by the initiation and promotion rodent model in accordance with previous reports (Diwan et al, 1986;Sakamoto et al, 2013;Tamura et al, 2015). We also investigated the involvement of CAR in liver hypertrophy induced by the same dose IMA.…”

Section: Experimental Procedures (Exps1 and 2)mentioning

confidence: 69%

“…The incidence and multiplicity (number of lesions per animal) of each proliferative lesion were calculated. Multiplicity was evaluated as a semi-quantitative analysis to make the difference of tumorigenesis clearer in the same manner as previous reports Tamura et al, 2015;Sakamoto et al, 2013).…”

Section: Pathological and Immunohistochemical Examination Of The Livermentioning

confidence: 99%

“…However, a recent report suggested that liver hypertrophy is not essential in hepatocarcinogenesis, but rather is associated with hepatocarcinogenesis (Elcombe et al, 2014). Our previous studies using C3H-derived CAR-knockout (CARKO) mice provided evidence that CAR is a main factor involved in liver tumor development induced by many compounds, including triazole fungicides, piperonyl butoxide (PBO), and Ginkgo biloba extract (GBE) (Sakamoto et al, 2013;Tamura et al, 2015;Maeda et al, 2015). Additionally, we found that liver hypertrophy induced by several compounds is not mediated by CAR (Sakamoto et al, 2013;Tamura et al, 2015), indicating that the pathway of liver hypertrophy is not always the same as that in tumor development.…”

Section: Introductionmentioning

confidence: 99%

“…The previous studies demonstrated that CARKO mice are a useful tool to clarify the involvement of other nuclear receptors in liver hypertrophy and tumor development, if the expression levels of several types of CYPs are investigated in the liver Sakamoto et al, 2013;Tamura et al, 2015;Maeda et al, 2015). Various chemicals activate multiple nuclear receptors and increase the expression of CYPs in the mouse liver.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

A crucial role of constitutive androstane receptor (CAR) in liver tumor development by imazalil in mice

et al. 2016

Self Cite

View full text Add to dashboard Cite

-To clarify the major pathway of liver tumor development induced by imazalil (IMA), an imidazole fungicide, male constitutive androstane receptor (CAR)-knockout (CARKO) and wild-type (WT) mice were treated with IMA at 500 ppm in the diet up to 27 weeks after initiation by diethylnitrosamine. After 27 weeks of treatment, neither altered foci nor adenomas were significantly increased in CARKO mice, whereas both eosinophilic altered foci and adenomas were increased in WT mice. After 4 or 13 weeks of IMA treatment, liver hypertrophy was observed at the tumor-inducible dose without differences among genotypes or durations. Analysis of hepatic drug metabolite enzymes, performed after administration of multiple doses during a 1-week period, indicated that pregnane X receptor might be involved in liver hypertrophy because IMA markedly elevated Cyp3a11 and Cyp2b10 expression levels in a dose-dependent manner in both genotypes. Our results demonstrated that the CAR pathway was the main mechanism of liver tumor development induced by IMA. The carcinogenic pathway was different from that of liver hypertrophy.

show abstract

Section: Discussionsupporting

confidence: 66%

Section: Experimental Procedures (Exps1 and 2)mentioning

confidence: 69%

Section: Pathological and Immunohistochemical Examination Of The Livermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A crucial role of constitutive androstane receptor (CAR) in liver tumor development by imazalil in mice

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

Microwave‐assisted‐demulsification dispersive liquid–liquid microextraction for the determination of triazole fungicides in water by gas chromatography with mass spectrometry

Wang

Zhao

Wang

et al. 2018

J of Separation Science

View full text Add to dashboard Cite

A novel microwave‐assisted‐demulsification dispersive liquid–liquid microextraction technique was established for determination of three triazole fungicides in environmental water samples by gas chromatography with mass spectrometry. Importantly, microwave irradiation has been applied in demulsification to achieve the phase separation and enrichment of triazole fungicides in water samples successfully with low‐density toluene as extractant. The experimental variables, including microwave power, microwave time, ultrasonic time, type and volume of extraction solvent, and effect of salting out were investigated. Under the optimized conditions, the method showed good linearity for myclobutanil, tebuconazole, and difenoconazole in the range of 1–100 μg/L. The limits of detection and the limits of quantification were within the range of 0.14–0.27 and 0.47–0.90 μg/L, respectively. The suitable enrichment factors for three triazole pesticides were in the range of 425–636. The recoveries were between 89.3 and 108.7%, and the relative standard deviations were from 5.4 to 8.6%. Finally, environmental water samples were used to verify the applicability of the proposed method for analysis of triazole fungicides targets. It can be concluded that the developed microwave‐assisted‐demulsification dispersive liquid–liquid microextraction gas chromatography with mass spectrometry method was a rapid, efficient, reliable, and environmental friendly way for analysis of triazole fungicides in water.

show abstract

Effects of tebuconazole on cytochrome P450 enzymes, oxidative stress, and endocrine disruption in male rats

Yang

Liu

Liao

et al. 2018

Environmental Toxicology

View full text Add to dashboard Cite

The major objective of the present study was to determine the ability of a triazole fungicide tebuconazole to induce cytochrome P450-dependent monooxygenases, oxidative stress, and endocrine-disrupting activity using male rats treated with tebuconazole at 10, 25, and 50 mg/kg p.o. once daily for 28 days. In liver, tebuconazole dose-dependently increased microsomal contents of cytochrome P450 and cytochrome b and the activities of NADPH-cytochrome P450 reductase, 7-ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase, pentoxyresorufin O-dealkylase, 7-ethoxycoumarin O-deethylase, aniline hydroxylase, and erythromycin N-demethylase. In kidney, tebuconazole increased 7-ethoxycoumarin O-deethylase activity without affecting other monooxygenase activities. In marked contrast to liver and kidney, tebuconazole decreased testicular 7-ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase, 7-ethoxycoumarin O-deethylase, aniline hydroxylase, and erythromycin N-demethylase activities. The results of immunoblot analysis of liver microsomes of controls and tebuconazole-treated rats revealed that tebuconazole induced CYP1A1/2, CYP2B1/2, CYP2E1, and CYP3A proteins in liver. Additions of tebuconazole to liver microsomes inhibited microsomal 7-ethoxycoumarin O-deethylase activity in vitro (IC = 1.50-1.69 µM). Treatment of rats with tebuconazole decreased glutathione content and increased glutathione S-transferase, superoxide dismutase, catalase, and glutathione peroxidase activities in liver; increased superoxide dismutase activities in kidney and testis; but decreased glutathione S-transferase activity in testis. Treatments with tebuconazole decreased serum testosterone concentration and cauda epididymal sperm count. The present study demonstrates that tebuconazole induces a multiplicity of CYPs and oxidative stress in liver; inhibits testicular P450 and glutathione S-transferase activities; and produces anti-androgenic effects in male rats.

show abstract

Involvement of constitutive androstane receptor in liver hypertrophy and liver tumor development induced by triazole fungicides

Cited by 28 publications

References 28 publications

A crucial role of constitutive androstane receptor (CAR) in liver tumor development by imazalil in mice

A crucial role of constitutive androstane receptor (CAR) in liver tumor development by imazalil in mice

Microwave‐assisted‐demulsification dispersive liquid–liquid microextraction for the determination of triazole fungicides in water by gas chromatography with mass spectrometry

Effects of tebuconazole on cytochrome P450 enzymes, oxidative stress, and endocrine disruption in male rats

Contact Info

Product

Resources

About