Department of Physiology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt.
Department of Clinical Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt.
Environ Sci Pollut Res Int. 2021 Jan;28(4):4558-4572. doi: 10.1007/s11356-020-10778-0. Epub 2020 Sep 18.
5-Fluorouracil (5-FU), a chemotherapeutic drug, has adverse effects on heart and kidney functions. Ficus Carica (fig) and extra virgin olive oil (EVOO) are natural sources which have antioxidant effects. This study investigated the synergistic effects of fig extract and EVOO against cardiac and renal damage induced by 5-FU. Forty rats were equally divided into five groups and treated with physiological saline (control), five intravenous injections of 5-FU (40 mg/kg b.w) (5-FU), fig (1 g/kg b.w/day, orally) with 5-FU (Fig/5-FU), EVOO (7 g/kg b.w/day, orally) with 5-FU (EVOO/5-FU), combined treatment of fig and EVOO with five 5-FU injections (Fig/EVOO/5-FU). After 30 days, blood and tissue samples (Heart and kidney) were collected to be used in the examinations. 5-FU significantly increased serum creatine kinase activity, renal biomarkers, cholesterol, triglycerides, C-reactive protein, tumor necrosis factor-α, and interleukin-1β as well as cardiac and renal lipid peroxides (malondialdehyde). Meanwhile, serum levels of immunoglobulins, interleukins (IL-10, IL-12), and antioxidants of heart and kidney tissues were significantly decreased in 5-FU group. It also downregulated cardiac and renal Bcl2, and upregulated cardiac troponin and renin gene expressions. As well, histological alterations clarified that 5-FU induced cardiac cell damage, distorted renal corpuscles and tubules, inflammatory cell infiltrations, and severe congestion and hemorrhage in the blood vessels. The treatment with fig and olive oil, especially the combined treatment, modulated the toxic effect of 5-FU on the heart and kidney. Our results revealed that fig extract and EVOO have a powerful antioxidant and many protective effects against cardiac and renal toxicity induced by 5-FU, especially when using fig and EVOO together as a combined treatment.
5-氟尿嘧啶(5-FU)是一种化疗药物,对心脏和肾脏功能有不良影响。榕属植物(无花果)和特级初榨橄榄油(EVOO)是具有抗氧化作用的天然来源。本研究探讨了无花果提取物和 EVOO 对 5-FU 诱导的心脏和肾脏损伤的协同作用。将 40 只大鼠等分为五组,分别用生理盐水(对照组)、5-FU(40mg/kg b.w)的五次静脉注射(5-FU)、无花果(1g/kg b.w/天,口服)与 5-FU(Fig/5-FU)、特级初榨橄榄油(7g/kg b.w/天,口服)与 5-FU(EVOO/5-FU)、无花果和特级初榨橄榄油联合治疗与五次 5-FU 注射(Fig/EVOO/5-FU)。30 天后,收集血液和组织样本(心脏和肾脏)进行检测。5-FU 显著增加血清肌酸激酶活性、肾脏生物标志物、胆固醇、甘油三酯、C 反应蛋白、肿瘤坏死因子-α和白细胞介素-1β以及心脏和肾脏脂质过氧化物(丙二醛)。同时,5-FU 组血清免疫球蛋白、白细胞介素(IL-10、IL-12)和心脏、肾脏组织抗氧化剂水平显著降低。它还下调了心脏和肾脏的 Bcl2,上调了心脏肌钙蛋白和肾素基因的表达。此外,组织学改变表明,5-FU 诱导心脏细胞损伤、扭曲肾脏肾小球和小管、炎症细胞浸润以及血管严重充血和出血。无花果和橄榄油的治疗,特别是联合治疗,调节了 5-FU 对心脏和肾脏的毒性作用。我们的结果表明,无花果提取物和 EVOO 具有强大的抗氧化作用,并对 5-FU 诱导的心脏和肾脏毒性具有多种保护作用,尤其是当将无花果和 EVOO 一起用作联合治疗时。