Mobasher Maysa A, Ahmed Eman Ibrahim, Hakami Nora Y, Germoush Mousa O, Awad Nabil S, Khodeer Dina M
Department of Pathology, Biochemistry Division, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia.
Pharmacology and Therapeutics Department, College of Medicine, Jouf University, Sakaka 72346, Saudi Arabia.
Metabolites. 2023 Jan 6;13(1):94. doi: 10.3390/metabo13010094.
Drug-induced liver damage is a life-threatening disorder, and one major form of it is the hepatotoxicity induced by the drug cisplatin. In folk medicine, Licorice ( (is used for detoxification and is believed to be a potent antioxidant. Currently, the magically self-renewable potential of bone marrow mesenchymal stem cells (BM-MSCs) has prompted us to explore their hepatoregenerative capability. The impact of extract (GGE) and BM-MSCs alone and, in combination, on protecting against hepatotoxicity was tested on cisplatin-induced liver injury in rats. Hepatic damage, as revealed by liver histopathology and increased levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and malondialdehyde (MDA), was elevated in rats by received 7 mg/kg of cisplatin intraperitoneally. The combination of GGE and BM-MSCs returned the enzyme levels to near the normal range. It also improved levels of liver superoxide dismutase (SOD) and glutathione (GSH) and reduced MDA levels. Additionally, it was found that when GGE and BM-MSCs were used together, they significantly downregulated caspase9 (Casp9), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), and interleukin-1β (IL-1β), which are involved in severe proinflammatory and apoptotic signaling cascades in the liver. Moreover, combining GGE and BM-MSCs led to the normal result of hepatocytes in several examined liver histological sections. Therefore, our findings suggest that GGE may have protective effects against oxidative liver damage and the promising regenerative potential of BM-MSCs.
药物性肝损伤是一种危及生命的疾病，其主要形式之一是顺铂诱导的肝毒性。在民间医学中，甘草用于解毒，被认为是一种有效的抗氧化剂。目前，骨髓间充质干细胞（BM-MSCs）神奇的自我更新潜力促使我们探索它们的肝再生能力。在顺铂诱导的大鼠肝损伤模型中，测试了甘草提取物（GGE）、BM-MSCs单独及联合应用对肝毒性的保护作用。腹腔注射7mg/kg顺铂可使大鼠肝脏组织病理学改变及血清天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、碱性磷酸酶（ALP）和丙二醛（MDA）水平升高，提示肝损伤加重。GGE与BM-MSCs联合应用可使上述酶水平恢复至接近正常范围。同时，联合应用还可提高肝脏超氧化物歧化酶（SOD）和谷胱甘肽（GSH）水平，降低MDA水平。此外，研究发现，GGE与BM-MSCs联合应用时，可显著下调参与肝脏严重促炎和凋亡信号级联反应的半胱天冬酶9（Casp9）、活化B细胞核因子κB（NF-κB）和白细胞介素-1β（IL-1β）。而且，GGE与BM-MSCs联合应用使多个肝脏组织学切片中的肝细胞结果恢复正常。因此，我们的研究结果表明，GGE可能对氧化型肝损伤具有保护作用，且BM-MSCs具有良好的再生潜力。
