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Alteration in the expression of cytochrome P450s (CYP1A1, CYP2E1, and CYP3A11) in the liver of mouse induced by microcystin-LR.

Zhang B, Liu Y, Li X - Toxins (Basel) (2015)

Bottom Line: Microcystins (MCs) are cyclic heptapeptide toxins and can accumulate in the liver.Cytochrome P450s (CYPs) play an important role in the biotransformation of endogenous substances and xenobiotics in animals.The result showed that MCLR significantly decreased ethoxyresorufin-O-deethylase (EROD) (CYP1A1) and erythromycin N-demthylase (ERND) (CYP3A11) activities and increased aniline hydroxylase (ANH) activity (CYP2E1) in the liver of mice during the period of exposure.

View Article: PubMed Central - PubMed

Affiliation: College of Life Science, Henan Normal University, Xinxiang 453007, Henan, China. 041129@htu.cn.

ABSTRACT
Microcystins (MCs) are cyclic heptapeptide toxins and can accumulate in the liver. Cytochrome P450s (CYPs) play an important role in the biotransformation of endogenous substances and xenobiotics in animals. It is unclear if the CYPs are affected by MCs exposure. The objective of this study was to evaluate the effects of microcystin-LR (MCLR) on cytochrome P450 isozymes (CYP1A1, CYP2E1, and CYP3A11) at mRNA level, protein content, and enzyme activity in the liver of mice the received daily, intraperitoneally, 2, 4, and 8 µg/kg body weight of MCLR for seven days. The result showed that MCLR significantly decreased ethoxyresorufin-O-deethylase (EROD) (CYP1A1) and erythromycin N-demthylase (ERND) (CYP3A11) activities and increased aniline hydroxylase (ANH) activity (CYP2E1) in the liver of mice during the period of exposure. Our findings suggest that MCLR exposure may disrupt the function of CYPs in liver, which may be partly attributed to the toxicity of MCLR in mice.

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Cytochrome P450 2E1 (CYP2E1) mRNA level (A); protein content (B); and aniline hydroxylase (ANH) activities (C) in mouse liver. Asterisks denote a response that is significantly different from the control (* p < 0.05, ** p < 0.01). CYP2E1 protein contents were normalized to β-actin followed by analysis of the relative intensity. The values indicated the fold change compared to the control (0 μg/kg).
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toxins-07-01102-f002: Cytochrome P450 2E1 (CYP2E1) mRNA level (A); protein content (B); and aniline hydroxylase (ANH) activities (C) in mouse liver. Asterisks denote a response that is significantly different from the control (* p < 0.05, ** p < 0.01). CYP2E1 protein contents were normalized to β-actin followed by analysis of the relative intensity. The values indicated the fold change compared to the control (0 μg/kg).

Mentions: CYP2E1 transcription was significantly up-regulated in the mice exposed to 4 μg/kg of MCLR for 1 day, 2 μg/kg MCLR for 7 days, or 4 and 8 µk/kg MCLR for 7 days (Figure 2A). Furthermore, CYP2E1 protein content was significantly increased in all MCLR-treated groups at 1, 3, and 7 day (Figure 2B). ANH activities increased in 4 and 8 μg/kg of MCLR groups after 3 days of exposure. After 7 days of exposure, ANH activities were significantly increased in all treatment groups (Figure 2C).


Alteration in the expression of cytochrome P450s (CYP1A1, CYP2E1, and CYP3A11) in the liver of mouse induced by microcystin-LR.

Zhang B, Liu Y, Li X - Toxins (Basel) (2015)

Cytochrome P450 2E1 (CYP2E1) mRNA level (A); protein content (B); and aniline hydroxylase (ANH) activities (C) in mouse liver. Asterisks denote a response that is significantly different from the control (* p < 0.05, ** p < 0.01). CYP2E1 protein contents were normalized to β-actin followed by analysis of the relative intensity. The values indicated the fold change compared to the control (0 μg/kg).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4417957&req=5

toxins-07-01102-f002: Cytochrome P450 2E1 (CYP2E1) mRNA level (A); protein content (B); and aniline hydroxylase (ANH) activities (C) in mouse liver. Asterisks denote a response that is significantly different from the control (* p < 0.05, ** p < 0.01). CYP2E1 protein contents were normalized to β-actin followed by analysis of the relative intensity. The values indicated the fold change compared to the control (0 μg/kg).
Mentions: CYP2E1 transcription was significantly up-regulated in the mice exposed to 4 μg/kg of MCLR for 1 day, 2 μg/kg MCLR for 7 days, or 4 and 8 µk/kg MCLR for 7 days (Figure 2A). Furthermore, CYP2E1 protein content was significantly increased in all MCLR-treated groups at 1, 3, and 7 day (Figure 2B). ANH activities increased in 4 and 8 μg/kg of MCLR groups after 3 days of exposure. After 7 days of exposure, ANH activities were significantly increased in all treatment groups (Figure 2C).

Bottom Line: Microcystins (MCs) are cyclic heptapeptide toxins and can accumulate in the liver.Cytochrome P450s (CYPs) play an important role in the biotransformation of endogenous substances and xenobiotics in animals.The result showed that MCLR significantly decreased ethoxyresorufin-O-deethylase (EROD) (CYP1A1) and erythromycin N-demthylase (ERND) (CYP3A11) activities and increased aniline hydroxylase (ANH) activity (CYP2E1) in the liver of mice during the period of exposure.

View Article: PubMed Central - PubMed

Affiliation: College of Life Science, Henan Normal University, Xinxiang 453007, Henan, China. 041129@htu.cn.

ABSTRACT
Microcystins (MCs) are cyclic heptapeptide toxins and can accumulate in the liver. Cytochrome P450s (CYPs) play an important role in the biotransformation of endogenous substances and xenobiotics in animals. It is unclear if the CYPs are affected by MCs exposure. The objective of this study was to evaluate the effects of microcystin-LR (MCLR) on cytochrome P450 isozymes (CYP1A1, CYP2E1, and CYP3A11) at mRNA level, protein content, and enzyme activity in the liver of mice the received daily, intraperitoneally, 2, 4, and 8 µg/kg body weight of MCLR for seven days. The result showed that MCLR significantly decreased ethoxyresorufin-O-deethylase (EROD) (CYP1A1) and erythromycin N-demthylase (ERND) (CYP3A11) activities and increased aniline hydroxylase (ANH) activity (CYP2E1) in the liver of mice during the period of exposure. Our findings suggest that MCLR exposure may disrupt the function of CYPs in liver, which may be partly attributed to the toxicity of MCLR in mice.

Show MeSH
Related in: MedlinePlus