坏死性下垂
利拉鲁肽
丙戊酸
愤怒(情绪)
药理学
HMGB1
医学
肝损伤
内科学
内分泌学
癌症研究
化学
程序性细胞死亡
细胞凋亡
神经科学
糖尿病
生物化学
生物
受体
2型糖尿病
癫痫
精神科
作者
Marwa Mohamed Atef,N. Abo Hashish,Yasser Mostafa Hafez,Ahmed Fawzy Selim,Hoda A. Ibrahim,Eman Fawzy Eltabaa,Fatma H. Rizk,Amany Mohamed Shalaby,Nadia M. Ezzat,Mohamed Ali Alabiad,Amira M. Elshamy
摘要
Valproic acid (VPA) is a commonly used drug for management of epilepsy. Prolonged VPA administration increases the risk of hepatotoxicity. Liraglutide is a glucagon-like peptide 1 receptor (GLP-1R) agonist that act as a novel antidiabetic drug with broad-spectrum anti-inflammatory and antioxidant effects. This study tested the protective effect of liraglutide against VPA-induced hepatotoxicity elucidating the possible underlying molecular mechanisms. Forty adult male rats were allocated in to four equally sized groups; Group I (control group) received oral distilled water and subcutaneous normal saline for 2 weeks followed by subcutaneous normal saline only for 2 weeks. Group II (liraglutide group) received subcutaneous liraglutide dissolved in normal saline daily for 4 weeks. Group III (valproic acid-treated group) received sodium valproate dissolved in distilled water for 2 weeks. Group IV (Combined valproic acid & liraglutide treated group) received valproic acid plus liraglutide daily for 2 weeks which was continued for additional 2 weeks after valproic acid administration. The hepatic index was calculated. Serum AST, ALT, GGT, and ALP activities were estimated. Hepatic tissue homogenate MDA, GSH, SOD, HMGB1, MAPK, RIPK1, and RIPK3 levels were evaluated using ELISA. However, hepatic RAGE and MLKL messenger RNA expression levels using the QRT-PCR technique. Hepatic NF-κB and TNF-α were detected immunohistochemically. Results proved that liraglutide coadministration significantly decreased liver enzymes, MDA, HMGB1, MAPK, RIPK1 RIPK3, RAGE, and MLKL with concomitant increased GSH and SOD in comparison to the correspondent values in VPA-hepatotoxicity group. Conclusions: Liraglutide's protective effects against VPA-induced hepatotoxicity are triggered by ameliorating oxidative stress, inflammation, and necroptosis.
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