Abstract

Morin is a flavonoid and broadly found in white berry and cranberry branch. Ifosfamide (IFOS) is known as an anticancer and cytotoxic drug especially on the liver. This study aimed to explore the potential protective effects of Morin against IFOS-induced liver toxicity in rats. The model group of rats received a single injection of IFOS (500 mg/kg; i.p.) at day 2, whereas the protective groups of rats were given two different doses of Morin (100 and 200 mg/kg; given by gavage) at days 1 and 2. All animals were then culled 24 h post-IFOS injection. We observed that IFOS caused liver injury, oxidative stress, inflammation, DNA damage, and apoptosis. However, Morin decreased the levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT) (p < 0.05). While Morin contributed to the recovery of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) levels, Morin decreased the levels of malondialdehyde (MDA) induced by IFOS in the liver (p < 0.05). Besides, the levels of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and P53 measured by ELISA test were reduced via Morin administration (p < 0.05). Lastly, the mRNA transcript levels of Bax, Apaf-1, Bcl-2, Bcl-xL, and inducible nitric oxide synthase (iNOS) determined by RT-PCR were down-regulated in the Morin groups (p < 0.05). These results indicate that Morin plays a protective role by reducing oxidative stress, inflammation, and apoptosis in the IFOS-induced liver injury in rats.

摘要

莫林是一种黄酮类化合物，广泛存在于白色浆果和蔓越莓枝中。异环磷酰胺 (IFOS) 被称为抗癌和细胞毒性药物，尤其是在肝脏上。本研究旨在探讨莫林对 IFOS 诱导的大鼠肝毒性的潜在保护作用。模型组大鼠在第2天单次注射IFOS（500 mg/kg；ip），而保护组大鼠在第2天给予两种不同剂量的Morin（100和200 mg/kg；灌胃） 1 和 2。然后在 IFOS 注射后 24 小时淘汰所有动物。我们观察到 IFOS 引起肝损伤、氧化应激、炎症、DNA 损伤和细胞凋亡。然而，Morin 降低了天冬氨酸氨基转移酶 (AST)、碱性磷酸酶 (ALP)、丙氨酸氨基转移酶 (ALT) 的水平（p < 0.05)。虽然 Morin 有助于恢复超氧化物歧化酶 (SOD)、过氧化氢酶 (CAT)、谷胱甘肽过氧化物酶 (GPx)、谷胱甘肽 (GSH) 水平，但 Morin 降低了 IFOS 诱导的肝脏中丙二醛 (MDA) 水平 ( p  < 0.05) . 此外，通过ELISA 试验测得的核因子 kappa B (NF-κB)、肿瘤坏死因子-α (TNF-α) 和 P53 的水平在Morin 给药下降低 ( p  < 0.05)。最后，通过 RT-PCR 测定的Bax、Apaf-1、Bcl-2、Bcl-xL和诱导型一氧化氮合酶 ( iNOS ) 的 mRNA 转录水平在 Morin 组中下调（p < 0.05)。这些结果表明，Morin 通过减少 IFOS 诱导的大鼠肝损伤中的氧化应激、炎症和细胞凋亡发挥保护作用。