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301286

HEPATOPROTECTIVE AND ANTIOXIDANT EFFECTS OF CAFFEINE AND SILYMARIN COMBINATION BY DECREASING LYSOPHOSPHATIDIC ACID RECEPTOR 3 TISSUE AND GENE EXPRESSION IN RATS

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Last updated: 25 Dec 2024

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Abstract

Liver disease causes about 2 million deaths yearly in the world. Caffeine (Caff) is the most common psychoactive substance utilized around the world. Caff has been demonstrated to possess anti-fibrotic actions in the liver. Silymarin (Sily) is a natural product largely used for its hepatoprotective actions through antioxidant, anti-inflammatory, and anti-fibrotic effects. Aim of the study: The current study aims to investigate the hepatoprotective and antioxidant effects of Caff and Sily alone or in combination in a rat model of liver fibrosis focusing on their effects on lysophosphatidic acid receptor 3 (LPAR3) expression. Materials and methods: 200 mg/kg of thioacetamide (TAA) was injected intraperitoneally twice weekly for 8 weeks to induce liver fibrosis. Caff, Sily, and their combination were orally administered to rats at a dose of 50 mg/kg/day for 8 weeks together with TAA injection. Results: Caff and Sily alone or in combination significantly improved liver function tests compared with fibrotic group. Moreover, they significantly decreased hepatic malondialdehyde (MDA) content and significantly increased the hepatic glutathione (GSH) concentration as compared with the fibrotic group. They significantly decreased fibrosis and necro-inflammatory scores with a superior significant effect in the necro-inflammatory score for the combination group each drug alone. Caff and Sily alone or in combination significantly decreased the hepatic LPAR3 gene and tissue expression, which was significantly correlated to their hepatoprotective effects. Conclusion: Caff and Sily alone or in combination protected against hepatic fibrosis through down-regulation of LPAR3 as well as antioxidant effects.

DOI

10.21608/bfsa.2023.301286

Keywords

Caffeine, glutathione, Liver fibrosis, Lysophosphatidic acid receptor, Malondialdehyde, Oxidative Stress, Silymarin

Authors

First Name

Salma

Last Name

Eraky

MiddleName

M.

Affiliation

Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt

Email

salmamossad@mans.edu.eg

City

-

Orcid

-

First Name

Mohamed

Last Name

El-Mesery

MiddleName

-

Affiliation

Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt

Email

-

City

-

Orcid

-

First Name

Amro

Last Name

El-Karef

MiddleName

-

Affiliation

Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt

Email

aelkaref@gmail.com

City

-

Orcid

-

First Name

Laila

Last Name

Eissa

MiddleName

A.

Affiliation

Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt

Email

lailaeissa2002@yahoo.com

City

-

Orcid

-

First Name

Amal

Last Name

El-Gayar

MiddleName

M.

Affiliation

Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt

Email

elgayaramal@gmail.com

City

-

Orcid

-

Volume

46

Article Issue

1

Related Issue

41495

Issue Date

2023-06-01

Receive Date

2023-01-20

Publish Date

2023-06-01

Page Start

615

Page End

631

Print ISSN

1110-0052

Online ISSN

3009-7703

Article File

BFSA_Volume 46_Issue 1_Pages 615-631.pdf

PDF . 1.6MB

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https://bpsa.journals.ekb.eg/article_301286.html

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https://bpsa.journals.ekb.eg/service?article_code=301286

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301,286

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Original Article

Type Code

1,096

Publication Type

Journal

Publication Title

Bulletin of Pharmaceutical Sciences Assiut University

Publication Link

https://bpsa.journals.ekb.eg/

MainTitle

HEPATOPROTECTIVE AND ANTIOXIDANT EFFECTS OF CAFFEINE AND SILYMARIN COMBINATION BY DECREASING LYSOPHOSPHATIDIC ACID RECEPTOR 3 TISSUE AND GENE EXPRESSION IN RATS

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Article

Created At

25 Dec 2024