Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Department of General Surgery, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, Shandong, China.
Environ Sci Pollut Res Int. 2021 Aug;28(29):39625-39636. doi: 10.1007/s11356-021-13392-w. Epub 2021 Mar 24.
Treatment with anti-neoplastic agents, including cyclophosphamide (CP), is associated with several adverse reactions. Here, we distinguished the potential protective effect of allicin against CP-mediated hepatotoxicity in rats. To assess the effect of allicin, four experimental groups were used, with 7 rats per group, including control, allicin (10 mg/kg), CP (200 mg/kg), and allicin + CP-treated groups. All groups were treated for 10 days. Blood and liver samples were collected for biochemical, molecular, and histological analyses. Treatment with CP led to deformations in the liver tissue that were associated with higher liver function markers (alanine transaminase, aspartate transaminase, and alkaline phosphatase). Additionally, a disturbance in the redox balance was observed after CP exposure, as indicated by increased levels of oxidants, including malondialdehyde and nitric oxide, and the decreased levels of endogenous antioxidants, including glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase. At the molecular level, CP treatment resulted in reduced expression of the Nrf2/ARE pathway and other genes related to this pathway, including NAD(P)H quinone dehydrogenase 1 and glutamate-cysteine ligase catalytic subunit. CP also led to a hyper-inflammatory response in hepatic tissue, with increased production of pro-inflammatory cytokines, including tumor necrosis factor-alpha and interlukin-1beta, and upregulation of nitric oxide synthase 2. CP also enhanced the immunoreactivity of the profibrogenic cytokine, transforming growth factor-beta, in liver tissue. Upregulation of caspase 3 and Bcl-2-associated X protein and downregulation of B-cell lymphoma 2 were also observed in response to CP treatment. Treatment with allicin reversed the molecular, biochemical, and histological changes that occurred with CP exposure. These results suggest that allicin can be used in combination with CP to avoid hepatotoxicity.
用抗肿瘤药物治疗，包括环磷酰胺（CP），与多种不良反应有关。在这里，我们研究了大蒜素对 CP 介导的大鼠肝毒性的潜在保护作用。为了评估大蒜素的作用，我们使用了四个实验组，每组 7 只大鼠，包括对照组、大蒜素（10mg/kg）组、CP（200mg/kg）组和大蒜素+CP 处理组。所有组均治疗 10 天。收集血液和肝脏样本进行生化、分子和组织学分析。CP 治疗导致肝组织变形，与更高的肝功能标志物（丙氨酸转氨酶、天冬氨酸转氨酶和碱性磷酸酶）相关。此外，CP 暴露后观察到氧化还原平衡失调，表现为氧化剂水平升高，包括丙二醛和一氧化氮，内源性抗氧化剂水平降低，包括谷胱甘肽、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、超氧化物歧化酶和过氧化氢酶。在分子水平上，CP 处理导致 Nrf2/ARE 通路和其他与该通路相关的基因表达降低，包括 NAD(P)H 醌脱氢酶 1 和谷氨酸-半胱氨酸连接酶催化亚基。CP 还导致肝组织中产生过度的促炎细胞因子，包括肿瘤坏死因子-α和白细胞介素-1β，并上调一氧化氮合酶 2。CP 还增强了肝组织中促纤维化细胞因子转化生长因子-β的免疫反应性。CP 处理还观察到 caspase 3 和 Bcl-2 相关 X 蛋白的上调和 B 细胞淋巴瘤 2 的下调。大蒜素治疗逆转了 CP 暴露引起的分子、生化和组织学变化。这些结果表明，大蒜素可以与 CP 联合使用以避免肝毒性。
