Amygdalin protects against acetaminophen-induced acute liver failure by reducing inflammatory response and inhibiting hepatocyte death
Amygdalin protects against acetaminophen-induced acute liver failure by reducing inflammatory response and inhibiting hepatocyte death
复制标题
苦杏仁苷通过减少炎症反应和抑制肝细胞死亡来预防对乙酰氨基酚引起的急性肝衰竭
DOI：
10.1016/j.bbrc.2022.03.011
复制
发表时间：
2022
影响因子：
3.1
通讯作者：
Gao Yueqiu
中科院分区：
文献类型：
--
作者：
Zhang Congcong;Lin Jiacheng;Zhen Chao;Wang Fang;Sun Xuehua;Kong Xiaoni;Gao Yueqiu
苦杏仁苷是苦杏籽中的一种天然化合物，据报道具有抗炎活性。对乙酰氨基酚（APAP）引起的药物性肝损伤是世界范围内急性肝衰竭（ALI）的主要原因，只有n -乙酰半胱氨酸是公认的解毒药物。然而，目前还没有有效的药物来改善肝细胞死亡和继发性炎症损伤。本研究旨在探讨苦杏仁苷对apap诱导的急性肝衰竭小鼠模型的保护作用。我们通过腹腔注射APAP建立ALI模型，并腹腔注射苦杏仁苷给药。检测肝酶及组织学变化评价肝损伤程度。我们测量了肝组织的氧化损伤标志物和炎症细胞浸润。最后探讨了苦杏仁苷对肝细胞的保护作用机制。结果表明，苦杏仁苷能降低肝组织ALT/AST水平，减少肝组织坏死面积。此外，苦杏仁苷降低肝脏MPO+（中性粒细胞）和F4/80+（巨噬细胞）的计数，抑制IL-6、TNF-a和IL-1b的表达。苦杏仁苷降低肝脏SOD和MDA水平，增加Nrf2/NQO1/HO1蛋白表达。此外，苦杏仁苷降低了肝组织中TUNEL+和P-MLKL +染色细胞。机制上，苦杏仁苷促进AKT磷酸化，抑制JNK/RIP3/MLKL信号通路。
Amygdalin is a natural compound from Bitter Apricot Seed which is reported to have anti-inflammatory activity. Acetaminophen (APAP) resulted in drug-induced liver injury is the main cause of acute liver failure (ALI) worldwide and only N-acetylcysteine is the accepted detoxification drug. However, there is no effective medicine to perfect the hepatocyte death and secondary inflammation injury. In this study, we aim to investigate the protective effect of Amygdalin in the APAP-induced acute liver failure mice model. We establish the ALI model via intraperitoneal APAP injection and mice were treated with Amygdalin with intraperitoneal injection. We detected liver enzyme and histological change to evaluate the liver injury. We measured oxidative damage markers and inflammatory cell infiltration of liver tissues. At last, we investigated the mechanism of Amygdalin on protecting hepatocytes. Results showed that Amygdalin reduced ALT/AST level and decreased necrotic area of liver tissue. In addition, Amygdalin reduced the count of MPO+(neutrophils) and F4/80+(macrophages) of the liver and inhibited IL-6, TNF-a, and IL-1b expression. Amygdalin reduced liver SOD and MDA levels and increased Nrf2/NQO1/HO1 protein expression. Moreover, Amygdalin reduced TUNEL+ and P-MLKL + staining cells in liver tissue. Mechanically, Amygdalin promoted phosphorylation of AKT and suppressed JNK/RIP3/MLKL signaling.