地奥司明单独或联合伊立替康对二甲基肼诱导的大鼠结肠癌的预防作用。

The preventive effects of diosmin alone or combined with irinotecan on 1,2-dimethylhydrazine-induced colon cancer in rats.

机构信息

Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt.

出版信息

Eur Rev Med Pharmacol Sci. 2024 Jul;28(14):4003-4021. doi: 10.26355/eurrev_202407_36576.

DOI:10.26355/eurrev_202407_36576

PMID:39081150

Abstract

OBJECTIVE

Colorectal cancer, one of the most frequently diagnosed cancers worldwide, has a high mortality rate. Thus, our research aims to examine the preventive effects of diosmin (DIO) alone and in conjunction with the anti-cancer drug irinotecan (camptothecin-11, CPT-11), on 1,2-dimethylhydrazine (DMH)-induced colon cancer (CC) in male Wistar rats.

MATERIALS AND METHODS

Fifty adult male Wistar rats were categorized into five groups. Group I (Normal) received saline 0.9 orally % as a vehicle once a week for 14 weeks. Group II (DMH) received DMH (20 mg/kg/week) orally dissolved in 0.9% saline for 14 weeks and 1% carboxymethylcellulose (CMC) every other day for the final 10 weeks. Group III (DMH+DIO) received DMH orally for 14 weeks and DIO (10 mg/kg, suspended in 1% CMC) every other day for the final 10 weeks. Group IV (DMH+CPT-11) received DMH orally for 14 weeks and intraperitoneal injection of CPT-11 (3 mg/kg) twice a week for the final 10 weeks. Group V (DMH+DIO+CPT-11) orally received DMH for 14 weeks and both DIO and CPT-11.

RESULTS

All treated groups showed a significant reduction (p<0.05) in their elevated serum malondialdehyde levels and significant amelioration (p<0.05) of their lowered activities of colon glutathione-S-transferase (GST) and glutathione reductase (GR) as well as serum glutathione level (GSH). In addition, simultaneous treatment with DIO and CPT-11 led to a significant decrease (p<0.05) in the elevated serum levels of carcinoembryonic antigen (CEA) in rats administered with DMH, as well as a reduction in the colon expression levels of the inflammatory mediator (NF-κB), cell proliferator protein (Ki-67), and proapoptotic protein (p53).

CONCLUSIONS

These findings suggest DIO, CPT-11, and their combination have anticarcinogenic effects against DMH-induced CC by suppressing oxidative stress, simulating the antioxidant defense system, attenuating the inflammatory effects, and reducing cell proliferation.

摘要

目的

结直肠癌是世界上最常见的癌症之一，死亡率很高。因此，我们的研究旨在研究地奥司明（DIO）单独使用以及与抗癌药物伊立替康（喜树碱-11，CPT-11）联合使用对雄性 Wistar 大鼠 1,2-二甲基肼（DMH）诱导的结肠癌（CC）的预防作用。

材料和方法

将 50 只成年雄性 Wistar 大鼠分为五组。第 I 组（正常）每周口服 0.9%生理盐水 0.9%作为载体一次，共 14 周。第 II 组（DMH）每周口服 DMH（20mg/kg/周）溶于 0.9%生理盐水，共 14 周，每隔一天口服 1%羧甲基纤维素（CMC）共 10 周。第 III 组（DMH+DIO）每周口服 DMH 14 周，每隔一天口服地奥司明（10mg/kg，悬浮于 1%CMC）共 10 周。第 IV 组（DMH+CPT-11）每周口服 DMH 14 周，每隔两周腹腔注射 CPT-11（3mg/kg）共 10 周。第 V 组（DMH+DIO+CPT-11）每周口服 DMH 14 周，同时口服地奥司明和 CPT-11。

结果

所有治疗组的血清丙二醛水平升高均显著降低（p<0.05），结肠谷胱甘肽-S-转移酶（GST）和谷胱甘肽还原酶（GR）活性以及血清谷胱甘肽水平（GSH）降低均显著改善（p<0.05）。此外，同时给予地奥司明和 CPT-11治疗可显著降低 DMH 处理大鼠血清癌胚抗原（CEA）水平升高（p<0.05），并降低结肠炎症介质（NF-κB）、细胞增殖蛋白（Ki-67）和促凋亡蛋白（p53）的表达水平。