Department of Medical Analysis, Princess Aisha Bint Al-Hussein College of Nursing and Health Sciences, Al-Hussein Bin Talal University, Ma'an, Jordan.
Department of Medical Analysis, Princess Aisha Bint Al-Hussein College of Nursing and Health Sciences, Al-Hussein Bin Talal University, Ma'an, Jordan; Department of Biology, College of Science, Al-Hussein Bin Talal University, Ma'an, Jordan.
Biomol Biomed. 2023 Jul 3;23(4):649-660. doi: 10.17305/bb.2022.8743.
Taxifolin (TA) is a natural flavonoid found in many foods and medicinal plants with well-documented antioxidant and anti-inflammatory properties. Cyclophosphamide (CP) is an effective antineoplastic and immunosuppressive agent; however, it is associated with numerous adverse events, including hepatotoxicity. Herein, we aimed to investigate the potential protective effects of TA using a mouse model of CP-induced hepatotoxicity. Mice were co-treated with TA (25 and 50 mg/kg, orally) and CP (30 mg/kg, i.p.) for 10 consecutive days and sacrificed 24 hours later. CP induced increased transaminases (ALT and AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) paralleled with pronounced histopathological alterations in the liver. Moreover, hepatic tissues of CP-injected mice showed increased malondialdehyde (MDA), protein carbonyl, and nitric oxide (NO) levels, accompanied by decreased antioxidant defenses (glutathione [GSH], superoxide dismutase [SOD], and catalase [CAT]). Livers of CP-injected mice also showed increased inflammatory response (nuclear transcription factor kappa-B [NF-κB] p65 activation, increased levels of proinflammatory cytokines tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1β], and IL-6) and apoptosis (decreased Bcl-2 and increased Bax and caspase-3 expression levels). Remarkably, TA ameliorated markers of liver injury and histological damage in CP-injected mice. TA treatment also attenuated numerous markers of oxidative stress, inflammation, and apoptosis in the liver of CP-injected mice. This was accompanied by increased nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) expression in the liver tissues of CP-injected mice. Taken together, this study indicates that TA may represent a promising new avenue to prevent/treat CP-induced hepatotoxicity and perhaps other liver diseases associated with oxidative stress and inflammation.
花旗松素（TA）是一种天然类黄酮，存在于许多食物和药用植物中，具有良好的抗氧化和抗炎特性。环磷酰胺（CP）是一种有效的抗肿瘤和免疫抑制剂；然而，它与许多不良反应有关，包括肝毒性。在此，我们旨在通过 CP 诱导的肝毒性小鼠模型来研究 TA 的潜在保护作用。小鼠连续 10 天接受 TA（25 和 50mg/kg，口服）和 CP（30mg/kg，腹腔注射）联合治疗，24 小时后处死。CP 诱导的丙氨酸转氨酶（ALT 和 AST）、碱性磷酸酶（ALP）和乳酸脱氢酶（LDH）升高，肝组织出现明显的组织病理学改变。此外，CP 注射小鼠的肝组织中丙二醛（MDA）、蛋白羰基和一氧化氮（NO）水平升高，抗氧化防御（谷胱甘肽[GSH]、超氧化物歧化酶[SOD]和过氧化氢酶[CAT]）水平降低。CP 注射小鼠的肝脏还表现出炎症反应增强（核转录因子 kappa-B [NF-κB] p65 激活，促炎细胞因子肿瘤坏死因子-α[TNF-α]、白细胞介素 1β[IL-1β]和白细胞介素 6[IL-6]水平升高）和细胞凋亡（Bcl-2 降低，Bax 和 caspase-3 表达水平升高）。值得注意的是，TA 改善了 CP 注射小鼠的肝损伤和组织学损伤标志物。TA 治疗还减轻了 CP 注射小鼠肝脏中许多氧化应激、炎症和细胞凋亡标志物。这伴随着 CP 注射小鼠肝组织中核因子红细胞 2 相关因子 2（Nrf2）/血红素加氧酶 1（HO-1）表达的增加。综上所述，这项研究表明，TA 可能代表一种有前途的新途径，可用于预防/治疗 CP 诱导的肝毒性，也许还可用于治疗其他与氧化应激和炎症相关的肝脏疾病。
