Saleh Nahed, Allam Tamer, Korany Reda M S, Abdelfattah Abdelfattah M, Omran Ahmed M, Abd Eldaim Mabrouk Attia, Hassan Aziza M, El-Borai Nermeen Borai
Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Sadat City, Sadat City 32897, Menoufia, Egypt.
Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
Pharmaceuticals (Basel). 2022 Feb 28;15(3):294. doi: 10.3390/ph15030294.
This study evaluates the antitumor efficacy of hesperidin (Hesp) versus cisplatin (Cis) in Ehrlich ascites carcinoma (EAC)-bearing mice, as well as its protective effect against Cis-triggered nephrotoxicity. Seventy female mice were allocated into control, Hesp, EAC, Hesp-protected, Hesp-treated, Cis-treated, and Cis+Hesp-treated groups. The inoculation of mice with EAC cells significantly reduced the mean survival time, while significantly increased the body weight, abdominal circumference, ascitic fluid volume, viable tumor cell count, and serum carcinoembryonic antigen, urea and creatinine levels, besides various hematological changes. Additionally, kidney tissue of EAC-bearing mice showed a significant increase in the malondialdehyde level, significant decreases in the reduced glutathione content and catalase activity, marked pathological alterations, and a strong Ki-67 expression with a weak caspase-3 expression in neoplastic cells infiltrating the renal capsule. Conversely, the administration of Hesp and/or Cis to the EAC-bearing mice induced, to various degrees, antitumor responses and alleviated the cytotoxic effects of EAC. In addition to the potent antitumor effect of the concomitant administration of Hesp and Cis, Hesp minimized the renal adverse side effects of Cis. In conclusion, Hesp may open new avenues for safe and effective cancer therapy and could be valuable for enhancing the antitumor potency and minimizing the renal adverse side effects of chemotherapeutic drugs.
本研究评估了橙皮苷(Hesp)和顺铂(Cis)对艾氏腹水癌(EAC)荷瘤小鼠的抗肿瘤疗效,以及Hesp对Cis引发的肾毒性的保护作用。将70只雌性小鼠分为对照组、Hesp组、EAC组、Hesp保护组、Hesp治疗组、Cis治疗组和Cis+Hesp治疗组。给小鼠接种EAC细胞显著缩短了平均生存时间,同时显著增加了体重、腹围、腹水体积、存活肿瘤细胞计数以及血清癌胚抗原、尿素和肌酐水平,此外还出现了各种血液学变化。此外,EAC荷瘤小鼠的肾组织丙二醛水平显著升高,还原型谷胱甘肽含量和过氧化氢酶活性显著降低,出现明显的病理改变,在浸润肾包膜的肿瘤细胞中Ki-67表达强烈而caspase-3表达微弱。相反,给EAC荷瘤小鼠施用Hesp和/或Cis在不同程度上诱导了抗肿瘤反应,并减轻了EAC的细胞毒性作用。除了Hesp和Cis联合给药具有强大的抗肿瘤作用外,Hesp还使Cis的肾脏不良副作用最小化。总之,Hesp可能为安全有效的癌症治疗开辟新途径,对于增强抗肿瘤效力和最小化化疗药物的肾脏不良副作用可能具有重要价值。