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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 3A11 (CYP3A11) mRNA level (A); protein content (B); and erythromycin N-demthylase (ERND) activities (C) in mouse liver. Asterisks denote a response that is significantly different from the control (* p < 0.05, ** p < 0.01). CYP3A11 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-f003: Cytochrome P450 3A11 (CYP3A11) mRNA level (A); protein content (B); and erythromycin N-demthylase (ERND) activities (C) in mouse liver. Asterisks denote a response that is significantly different from the control (* p < 0.05, ** p < 0.01). CYP3A11 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: After 1 day of MCLR exposure, CYP3A11 transcription was remarkably suppressed in 2 and 4 µg/kg groups, while promoted in 8 µg/kg group, but it remained unchanged after 3 days. However, at the end of exposure, it was significantly up-regulated again in all treatment groups, when compared to the control group (Figure 3A). The protein content of CYP3A11 decreased in a dose-dependent manner in almost all treatment groups from 1 to 7 days of exposure in comparison with control groups (Figure 3B). In a similar way, ERND activity decreased in almost all treatment groups throughout the period of test (Figure 3C).


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 3A11 (CYP3A11) mRNA level (A); protein content (B); and erythromycin N-demthylase (ERND) activities (C) in mouse liver. Asterisks denote a response that is significantly different from the control (* p < 0.05, ** p < 0.01). CYP3A11 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-f003: Cytochrome P450 3A11 (CYP3A11) mRNA level (A); protein content (B); and erythromycin N-demthylase (ERND) activities (C) in mouse liver. Asterisks denote a response that is significantly different from the control (* p < 0.05, ** p < 0.01). CYP3A11 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: After 1 day of MCLR exposure, CYP3A11 transcription was remarkably suppressed in 2 and 4 µg/kg groups, while promoted in 8 µg/kg group, but it remained unchanged after 3 days. However, at the end of exposure, it was significantly up-regulated again in all treatment groups, when compared to the control group (Figure 3A). The protein content of CYP3A11 decreased in a dose-dependent manner in almost all treatment groups from 1 to 7 days of exposure in comparison with control groups (Figure 3B). In a similar way, ERND activity decreased in almost all treatment groups throughout the period of test (Figure 3C).

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