Details
| Original language | English |
|---|---|
| Article number | 5514248 |
| Pages (from-to) | 5514248 |
| Journal | Oxidative Medicine and Cellular Longevity |
| Volume | 2023 |
| Publication status | Published - 22 Aug 2023 |
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.
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In: Oxidative Medicine and Cellular Longevity, Vol. 2023, 5514248, 22.08.2023, p. 5514248.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Erythropoietin Suppresses the Hepatic Fibrosis Caused by Thioacetamide
T2 - Role of the PI3K/Akt and TLR4 Signaling Pathways
AU - Elbaset, Marawan A.
AU - Mohamed, Bassim M. S. A.
AU - Moustafa, Passant E.
AU - Mansour, Dina F.
AU - Afifi, Sherif M.
AU - Esatbeyoglu, Tuba
AU - Abdelrahman, Sahar S. M.
AU - Fayed, Hany M.
N1 - The authors would like to thank Science Shake Inc. for conducting proofreading and English language editing (https://science-shake.com/). The publication of this article was funded by the Open Access Fund of Leibniz Universität Hannover. “The funders had no role in study design, data collection, and analysis, the decision to publish, or preparation of the manuscript.”
PY - 2023/8/22
Y1 - 2023/8/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85169503327&partnerID=8YFLogxK
U2 - 10.1155/2023/5514248
DO - 10.1155/2023/5514248
M3 - Article
VL - 2023
SP - 5514248
JO - Oxidative Medicine and Cellular Longevity
JF - Oxidative Medicine and Cellular Longevity
SN - 1942-0900
M1 - 5514248
ER -