<abstract xmlns="http://www.w3.org/1999/xhtml">

<bold>Objective.</bold> Carbamazepine (CBZ), a widely used antiepileptic drug, is one major cause of the idiosyncratic liver injury along with immune reactions. Conversely, prostaglandin E2 (PGE2) demonstrates a hepatoprotective effect by regulating immune reactions and promoting liver repair in various types of liver injury. However, the amount of hepatic PGE2 during CBZ-induced liver injury remains elusive. In this study, we aimed to evaluate the hepatic PGE2 levels during CBZ-induced liver injury using a mouse model.
<bold>Methods.</bold> Mice were orally administered with CBZ at a dose of 400 mg/kg for 4 days, and 800 mg/kg on the 5th day.
<bold>Results.</bold> Plasma alanine transaminase (ALT) level increased in some of mice 24 h after the last CBZ administration. Although median value of hepatic PGE2 amount in the CBZ-treated mice showed same extent as vehicle-treated control mice, it exhibited significant elevated level in mice with severe liver injury presented by a plasma ALT level >1000 IU/L. According to these results, mice had a plasma ALT level >1000 IU/L were defined as responders and the others as non-responders in this study. Even though, the hepatic PGE2 levels increased in responders, the hepatic expression and enzyme activity related to PGE2 production were not upregulated when compared with vehicle-treated control mice. However, the hepatic 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression and activity decreased significantly in responders when compared with control mice.
<bold>Conclusions.</bold> These results indicate that elevated hepatic PGE2 levels can be attributed to the downregulation of 15-PGDH expression under CBZ-induced liver injury.
</abstract>

Objective. Carbamazepine (CBZ), a widely used antiepileptic drug, is one major cause of the idiosyncratic liver injury along with immune reactions. Conversely, prostaglandin E2 (PGE2) demonstrates a hepatoprotective effect by regulating immune reactions and promoting liver repair in various types of liver injury. However, the amount of hepatic PGE2 during CBZ-induced liver injury remains elusive. In this study, we aimed to evaluate the hepatic PGE2 levels during CBZ-induced liver injury using a mouse model.
Methods. Mice were orally administered with CBZ at a dose of 400 mg/kg for 4 days, and 800 mg/kg on the 5th day.
Results. Plasma alanine transaminase (ALT) level increased in some of mice 24 h after the last CBZ administration. Although median value of hepatic PGE2 amount in the CBZ-treated mice showed same extent as vehicle-treated control mice, it exhibited significant elevated level in mice with severe liver injury presented by a plasma ALT level >1000 IU/L. According to these results, mice had a plasma ALT level >1000 IU/L were defined as responders and the others as non-responders in this study. Even though, the hepatic PGE2 levels increased in responders, the hepatic expression and enzyme activity related to PGE2 production were not upregulated when compared with vehicle-treated control mice. However, the hepatic 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression and activity decreased significantly in responders when compared with control mice.
Conclusions. These results indicate that elevated hepatic PGE2 levels can be attributed to the downregulation of 15-PGDH expression under CBZ-induced liver injury.

Assessment of hepatic prostaglandin E2 level in carbamazepine induced liver injury

Department of Pharmacy, Faculty of Pharmacy

Takasaki University of Health and Welfare

Endocrine Regulations

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Assessment of hepatic prostaglandin E level in carbamazepine induced liver injury

Objective. Carbamazepine (CBZ), a widely used antiepileptic drug, is one major cause of the idiosyncratic liver injury along with immune reactions. Conversely,...

Assessment of hepatic prostaglandin E₂ level in carbamazepine induced liver injury

Data publikacji: 18 lut 2022

Zakres stron: 22 - 30

DOI: https://doi.org/10.2478/enr-2022-0003

Słowa kluczowe
liver injury, prostaglandin E, carbamazepine, 15-PGDH

© 2022 Ken-ichi Oba et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Assessment of hepatic prostaglandin E2 level in carbamazepine induced liver injury

Data publikacji: 18 lut 2022

Zakres stron: 22 - 30

DOI: https://doi.org/10.2478/enr-2022-0003

Słowa kluczoweliver injury, prostaglandin E, carbamazepine, 15-PGDH

© 2022 Ken-ichi Oba et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Assessment of hepatic prostaglandin E₂ level in carbamazepine induced liver injury

Słowa kluczowe
liver injury, prostaglandin E, carbamazepine, 15-PGDH