Article ; Online: The implication of LPS/TLR4 and FXR receptors in hepatoprotective efficacy of indole-3-acetic acid and chenodeoxycholic acid.
2023 Volume 334, Page(s) 122182
Abstract: Aim: Valproic acid (VPA) belongs to the first-generation antiepileptic drugs, yet its prolonged use can cause life-threatening liver damage. The importance of our study is to investigate the protective effect of indole-3-acetic acid (IAA), ... ...
| Abstract | Aim: Valproic acid (VPA) belongs to the first-generation antiepileptic drugs, yet its prolonged use can cause life-threatening liver damage. The importance of our study is to investigate the protective effect of indole-3-acetic acid (IAA), chenodeoxycholic acid (CDCA) and their combination on VPA-induced liver injury focusing on lipopolysaccharides (LPS)/toll-like receptor 4 (TLR4) pathway and farnesoid X receptor (FXR). Methods: Thirty rats were randomly assigned into five groups, normal control group, VPA group received 500 mg/kg of VPA intraperitoneally. The remaining groups were orally treated with either 40 mg/kg of IAA, 90 mg/kg of CDCA, or a combination of both, along with VPA. All treatments were administered one hour after the administration of VPA for three weeks. Key findings: VPA group showed significant elevations in the liver weight/body weight ratio, serum aminotransferases, triglyceride, and total cholesterol levels. Hepatic glutathione (GSH) level and superoxide dismutase (SOD) activity were significantly decreased, while malondialdehyde (MDA) level, tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β), lipopolysaccharide (LPS) and caspase 3 were significantly increased. Likewise, immunohistochemical analysis revealed that TLR4 expression was elevated, whereas FXR expression was downregulated in hepatocytes. IAA substantially ameliorated all previously altered parameters, whereas CDCA treatment showed a partial improvement compared to IAA. Surprisingly, combination therapy of IAA with CDCA showed an additive effect only in the hepatic expression of TLR4 and FXR proteins. Significance: IAA could be a promising protective agent against VPA-induced liver injury. |
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| MeSH term(s) | Rats ; Animals ; Lipopolysaccharides/pharmacology ; Chenodeoxycholic Acid/pharmacology ; Chenodeoxycholic Acid/metabolism ; Toll-Like Receptor 4/metabolism ; Chemical and Drug Induced Liver Injury, Chronic/metabolism ; Liver/metabolism ; Glutathione/metabolism | |||||
| Chemical Substances | Lipopolysaccharides ; Chenodeoxycholic Acid (0GEI24LG0J) ; Toll-Like Receptor 4 ; indoleacetic acid (6U1S09C61L) ; Glutathione (GAN16C9B8O) | |||||
| Language | English | |||||
| Publishing date | 2023-10-18 | |||||
| Publishing country | Netherlands | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 3378-9 | |||||
| ISSN | 1879-0631 ; 0024-3205 | |||||
| ISSN (online) | 1879-0631 | |||||
| ISSN | 0024-3205 | |||||
| DOI | 10.1016/j.lfs.2023.122182 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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