Erythropoietin Suppresses the Hepatic Fibrosis Caused by Thioacetamide

Role of the PI3K/Akt and TLR4 Signaling Pathways

authored by

Marawan A. Elbaset, Bassim M. S. A. Mohamed, Passant E. Moustafa, Dina F. Mansour, Sherif M. Afifi, Tuba Esatbeyoglu, Sahar S. M. Abdelrahman, Hany M. Fayed

Abstract

Erythropoietin (EPO) is recognized for its function in erythropoiesis; however, its potential antifibrotic effect against liver fibrosis remains unknown. This study examined whether EPO affects thioacetamide (TAA)-induced liver fibrosis by concentrating on the Toll-like receptor 4 (TLR4) cascade and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway as possible pathways. Male Wistar rats were randomized into four groups, which included: the negative control group, the TAA group (intraperitoneal; TAA 100 mg/kg three times per week for 2 weeks), and EPO-treated groups (150 and 300 IU/kg, i.p.) for 2 weeks after TAA injections. EPO attenuated hepatic fibrosis in a dosage-dependent way, as manifested by the diminution in serum alanine aminotransferase and aspartate aminotransferase activities, as well as the increase in albumin level. EPO inhibited the increase in tissue levels of tumor necrosis factors-α, interleukin-1β, transforming growth factor-β1, and TLR4 and raised tissue levels of PI3K and p-PI3K. EPO antioxidant properties were demonstrated by restoring hepatic glutathione and superoxide dismutase by preventing the accumulation of hepatic malondialdehyde. Further, EPO increased the protein expression of PI3K and Akt and decreased TLR4 protein expression. Immunohistochemically, EPO treatment altered tissue histology and downregulated mitogen-activated protein kinase protein expression. Overall, the research suggested that EPO could prevent TAA-induced hepatic fibrosis through upregulating the PI3K/Akt signaling cascade and downregulation the TLR4 downstream axis.

Organisation(s)

Institute of Food Science and Human Nutrition
Molecular Food Chemistry and Food Development

External Organisation(s)

National Research Centre (NRC)
Galala University (GU)
University of Sadat City
Cairo University

Type

Article

Journal

Oxidative Medicine and Cellular Longevity

Volume

2023

Pages

5514248

ISSN

1942-0900

Publication date

22.08.2023

Publication status

Published

Peer reviewed

Yes

Electronic version(s)

https://doi.org/10.1155/2023/5514248 (Access: Open)