Department of Zoology, Faculty of Science, South Valley University, Qena 83523, Egypt.
Department of Pathology & Clinical Pathology, Faculty of Veterinary Medicine, South Valley University, Qena 83523, Egypt.
Biomed Pharmacother. 2018 Jan;97:53-59. doi: 10.1016/j.biopha.2017.10.134. Epub 2017 Nov 6.
Cyclophosphamide (CP), a chemotherapeutic agent, induces hepatotoxicity as one of its side effects. Therefore, the aim of the present study is to investigate the potential hepatoprotective effects of fullerene C nanoparticles (C) against the high toxic dose of CP. Twenty five albino rats were randomly assigned to 5 groups (n=5 per group). Group 1 served as a control. Group 2 received 200mg/kg of CP once intraperitoneally, while group 3 treated with the same CP dose plus C (4mgkg, orally) daily for 10days. Group 4 exposed CP and ZnCl (4mgkg, orally) daily for 10days. Group 5 exposed to CP and co-treated with C and ZnCl. One day after last treatment, blood and livers were collected for hematological, biochemical and histopathological investigations. C normalized significantly RBCs, HB, PCV, WBCs and platelets numbers compared to CP-exposed rats. Moreover, liver enzymes namely ALT, AST and ALP revealed that CP elevated their levels and C significantly (p<0.05) reduced them to basal levels. The level of oxidative stress marker namely, MDA was elevated upon CP exposure and normalized by C treatment. In addition, antioxidant systems e.g. GSH, CAT and SOD were depleted from liver tissue due to CP toxicity these were recovered by C administration. The hepatoprotective effects of C on tested parameters were comparable with ZnCl and neither additive nor synergistic effect was observed. Histopathogically, severe liver degeneration was recorded after CP treatment, however, only mild changes were observed after C administration. Our data suggest that C improves both blood and hepatic parameters altered by cyclophosphamide-induced toxicities. The current study is of clinical relevance particularly, application of C as a monotherapy or in combination to ameliorate the CP side effects in cancer-treated patients.
环磷酰胺(CP)是一种化疗药物,其副作用之一是肝毒性。因此,本研究旨在探讨富勒烯 C 纳米粒子(C)对 CP 高毒性剂量的潜在肝保护作用。25 只白化大鼠随机分为 5 组(每组 5 只)。第 1 组为对照组。第 2 组腹腔注射 200mg/kg CP 一次,第 3 组同时给予相同 CP 剂量加 C(4mg/kg,口服)每日 10 天。第 4 组暴露于 CP 和 ZnCl(4mg/kg,口服)每日 10 天。第 5 组暴露于 CP 并联合 C 和 ZnCl 治疗。最后一次治疗后 1 天,采集血液和肝脏进行血液学、生化和组织病理学研究。C 使 RBCs、HB、PCV、WBCs 和血小板数量与 CP 暴露大鼠相比显著正常化。此外,肝酶即 ALT、AST 和 ALP 表明 CP 升高了它们的水平,而 C 显著(p<0.05)将其降低到基础水平。氧化应激标志物 MDA 的水平在 CP 暴露时升高,并通过 C 处理得到正常化。此外,由于 CP 毒性,抗氧化系统如 GSH、CAT 和 SOD 从肝组织中耗尽,这些在 C 给药后得到恢复。C 对测试参数的保肝作用与 ZnCl 相当,没有观察到相加或协同作用。组织病理学上,CP 治疗后记录到严重的肝变性,但 C 给药后仅观察到轻度变化。我们的数据表明,C 改善了环磷酰胺诱导的毒性改变的血液和肝脏参数。本研究具有临床相关性,特别是应用 C 作为单一疗法或联合疗法来改善癌症治疗患者的 CP 副作用。