Pharmacology Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Sharkia, Egypt.
Cytology & Histology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt.
Biomed Pharmacother. 2017 Feb;86:482-491. doi: 10.1016/j.biopha.2016.12.038. Epub 2016 Dec 23.
Cisplatin (cis-diamminedichloroplatinum, CDDP) is an effective DNA alkylating agent used in the treatment of different types of tumors; however, its clinical use is associated with hepato-cardiotoxicity. The current study was designed to assess the potential protective effect of parsley oil (PO) against CDDP-induced hepato-cardiotoxicity. For this purpose, 25 adult male rats were assigned into five groups, each containing five animals. Group I (control) was administered saline solution. Group II was administered PO at a dosage of 0.42ml/kg BW. Group III were administered CDDP at a dosage of 5mg/kg BW. Group IV was administered PO in addition to CDDP. Group V was administered saline solution in addition to CDDP, after which they were administered PO for five days. Oral administration of either saline solution or PO was performed each day for 10days, while administration of CDDP was via a single intraperitoneal injection five days following the commencement of the experiment. The recorded results revealed that CDDP induced obvious hepatic and cardiac injuries that were indicated by biochemical, histopathological, and immunohistochemical alterations, including elevation of serum hepatic and cardiac injury markers as well as proinflammatory cytokines. Moreover, CDDP induced an increase in the level of hepatic and cardiac injury biomarkers, decreases in the activities of antioxidant enzymes, a decrease in GSH concentration, and an increase in MDA concentration. CDDP also induced histopathological hepatocellular and myocardial changes, and overexpression of p53 and COX-2 in hepatic and cardiac tissues. Administration of PO either as a preventative medicine or as treatment significantly improved all the observed deleterious effects induced by CDDP in rat liver and heart. Thus, it may be concluded that PO, with its antioxidant, anti-inflammatory, and antiapoptotic activities, can potentially be used in the treatment of CDDP-induced hepatic and cardiac injuries.
顺铂（cis-diamminedichloroplatinum，CDDP）是一种有效的 DNA 烷化剂，用于治疗不同类型的肿瘤；然而，其临床应用与肝心脏毒性有关。本研究旨在评估欧芹油（PO）对 CDDP 诱导的肝心脏毒性的潜在保护作用。为此，将 25 只成年雄性大鼠分为五组，每组 5 只。第 I 组（对照组）给予生理盐水。第 II 组给予 0.42ml/kg BW 的 PO。第 III 组给予 5mg/kg BW 的 CDDP。第 IV 组给予 PO 加 CDDP。第 V 组在给予 CDDP 后给予生理盐水加 PO，共 5 天。每天口服生理盐水或 PO，共 10 天，而 CDDP 则通过单次腹腔注射给药，在实验开始后的第五天进行。记录的结果表明，CDDP 诱导明显的肝和心脏损伤，这表现为生化、组织病理学和免疫组织化学改变，包括血清肝和心脏损伤标志物以及促炎细胞因子的升高。此外，CDDP 诱导肝和心脏损伤生物标志物水平升高，抗氧化酶活性降低，GSH 浓度降低，MDA 浓度升高。CDDP 还诱导肝和心肌组织的组织病理学变化，以及 p53 和 COX-2 在肝和心脏组织中的过表达。PO 无论是作为预防药物还是治疗药物给药，都能显著改善 CDDP 对大鼠肝脏和心脏引起的所有观察到的有害影响。因此，可以得出结论，PO 具有抗氧化、抗炎和抗凋亡作用，可能用于治疗 CDDP 诱导的肝和心脏损伤。
