Bakir Murat, Geyikoglu Fatime, Koc Kubra, Cerig Salim
Department of Biology, Faculty of Science, Ataturk University, Erzurum, Turkey.
J Cancer Res Ther. 2018 Apr-Jun;14(3):671-678. doi: 10.4103/jcrt.JCRT_1040_16.
Cisplatin (CIS) is an influential chemotherapeutic agent in the treatment of several types of malignant solid tumors, but its clinical use is related with ototoxicity. Oleuropein (OLE) is a natural antioxidant and scavenging free radicals. Here, we first explore the efficacy of OLE in pancreas against to the toxicity of CIS and also analyses its mechanism.
Fifty-six Sprague-Dawley rats were equally divided into eight groups, including, control group which received 7 mg/kg/day CIS intraperitoneally (i.p.) for 24 h, groups treated with doses of 50, 100, and 200 mg/kg OLE i.p. for 3 days, and groups which received same dose of CIS with three doses of OLE. After the treatments, animals were sacrificed. The oxidative DNA damage (8-hydroxy-2'-deoxyguanosine [8-OHdG]), total oxidative stress (TOS), total antioxidant status (TAS), and malondialdehyde (MDA) levels were evaluated in the pancreas. The histopathology of the pancreas was examined using three different staining methods: hematoxylin-eosin, periodic acid-Schiff, and alcian blue. Serum was provided to assess pancreatic function the lipase and amylase values.
The results showed that CIS significantly increased the level of TOS, MDA, and 8-OHdG in tissue as compared to the control group. Moreover, severe tissue damages were detected in the pancreas. Whereas, OLE at high dose significantly decreased the formations of 8-OHdG, the level of MDA, and increased levels of TAS in tissue samples. In the CIS group, the levels of amylase and lipase increased compared with the control group. However, there were statistically significant differences among the CIS group and the CIS + OLE groups in the values of both amylase and lipase. In addition, histopathological findings observed in CIS group in the pancreatic tissue alleviated in CIS + OLE groups.
We hope that the results of this study will provide an impetus for future investigations of novel treatment strategies for OLE in pancreas due to CIS.
顺铂(CIS)是治疗多种恶性实体瘤的一种有影响力的化疗药物,但其临床应用与耳毒性有关。橄榄苦苷(OLE)是一种天然抗氧化剂,可清除自由基。在此,我们首先探讨OLE对胰腺中CIS毒性的疗效,并分析其作用机制。
56只Sprague-Dawley大鼠平均分为八组,包括腹腔注射(i.p.)7 mg/kg/天CIS共24小时的对照组,腹腔注射50、100和200 mg/kg OLE共3天的组,以及接受相同剂量CIS和三剂OLE的组。治疗后,处死动物。评估胰腺中的氧化DNA损伤(8-羟基-2'-脱氧鸟苷[8-OHdG])、总氧化应激(TOS)、总抗氧化状态(TAS)和丙二醛(MDA)水平。使用苏木精-伊红、过碘酸-希夫和阿尔辛蓝三种不同染色方法检查胰腺的组织病理学。提供血清以评估胰腺功能的脂肪酶和淀粉酶值。
结果显示,与对照组相比,CIS显著增加了组织中TOS、MDA和8-OHdG的水平。此外,在胰腺中检测到严重的组织损伤。而高剂量的OLE显著降低了组织样本中8-OHdG的形成、MDA水平,并增加了TAS水平。在CIS组中,淀粉酶和脂肪酶水平与对照组相比有所升高。然而,CIS组和CIS + OLE组在淀粉酶和脂肪酶值方面存在统计学显著差异。此外,CIS组胰腺组织中观察到的组织病理学结果在CIS + OLE组中得到缓解。
我们希望本研究结果将为未来研究OLE对胰腺中CIS的新型治疗策略提供动力。