鹅去氧胆酸
法尼甾体X受体
化学
丙二醛
内分泌学
药理学
内科学
谷胱甘肽
肝损伤
胆汁酸
TLR4型
受体
生物化学
抗氧化剂
医学
核受体
转录因子
基因
酶
作者
Amjad S. Aljarboa,Ahlam M. Alhusaini,Wedad S. Sarawi,Raeesa Ahmed,Rehab A. Ali,Iman H. Hasan
出处
期刊:Life Sciences
[Elsevier]
日期:2023-12-01
卷期号:334: 122182-122182
标识
DOI:10.1016/j.lfs.2023.122182
摘要
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).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.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.IAA could be a promising protective agent against VPA-induced liver injury.
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