Department of Biochemistry, Faculty of Veterinary Medicine, Bingol University, Bingol, Turkey.
Department of Solhan School of Health Services, Bingol University, Bingol, Turkey.
Environ Sci Pollut Res Int. 2018 Jul;25(21):20968-20984. doi: 10.1007/s11356-018-2242-5. Epub 2018 May 15.
Cyclophosphamide (CP) is a common chemotherapeutic agent that is effective against a wide variety of tumors. The associated hepatotoxicity and nephrotoxicity, however, limit its therapeutic use. Naringin (NG) is a natural flavanone glycoside that has pharmacological and therapeutic activities, such as anti-inflammation, anti-apoptotic, and antioxidant properties. Therefore, the present study was undertaken to evaluate the protective effect of NG against CP-induced hepatotoxicity and nephrotoxicity in rats. Rats were pre-treated with NG (50 and 100 mg/kg b.w.) for 7 days before administering a single dose of CP (200 mg/kg b.w.) on the seventh day. CP-induced hepatotoxicity and nephrotoxicity were associated with an increase in serum toxicity markers and a decrease in antioxidant enzyme activities. CP also induced inflammatory responses by increasing the levels of tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, it activated the apoptotic and autophagic pathway by increasing cysteine aspartate-specific protease-3 (caspase-3) expression and light chain 3B (LC3B) level and also increased the expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is the marker of oxidative DNA damage. Pre-treatment with NG (50 and 100 mg/kg), however, significantly decreased serum toxicity markers, increased antioxidant enzyme activities, and regulated inflammation, apoptosis, autophagy, and oxidative DNA damage in hepatic and renal tissues. These results indicated that NG was an effective protectant against CP-induced hepatotoxicity and nephrotoxicity.
环磷酰胺（CP）是一种常用的化疗药物，对多种肿瘤有效。然而，其相关的肝毒性和肾毒性限制了其治疗用途。柚皮苷（NG）是一种天然类黄酮糖苷，具有药理学和治疗作用，如抗炎、抗凋亡和抗氧化特性。因此，本研究旨在评估 NG 对 CP 诱导的大鼠肝毒性和肾毒性的保护作用。大鼠在第 7 天给予 CP（200mg/kg b.w.）前，预先用 NG（50 和 100mg/kg b.w.）预处理 7 天。CP 诱导的肝毒性和肾毒性与血清毒性标志物的增加和抗氧化酶活性的降低有关。CP 还通过增加肿瘤坏死因子-α（TNF-α）、核因子 kappa B（NF-κB）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）的水平以及诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）的活性来诱导炎症反应。此外，它通过增加半胱氨酸天冬氨酸特异性蛋白酶-3（caspase-3）表达和轻链 3B（LC3B）水平来激活凋亡和自噬途径，还增加了 8-羟基-2'-脱氧鸟苷（8-OHdG）的表达，这是氧化 DNA 损伤的标志物。然而，NG（50 和 100mg/kg）预处理显著降低了血清毒性标志物，增加了抗氧化酶活性，并调节了肝和肾组织中的炎症、凋亡、自噬和氧化 DNA 损伤。这些结果表明，NG 是 CP 诱导的肝毒性和肾毒性的有效保护剂。
