Protective and Therapeutic Efficacy of Hesperidin versus Cisplatin against Ehrlich Ascites Carcinoma-Induced Renal Damage in Mice.

Ahmed M Omran,Nermeen Borai El-Borai,Reda M S Korany,Tamer Allam,Aziza M Hassan,Nahed Saleh,Abdelfattah M Abdelfattah,Mabrouk Attia Abd Eldaim

doi:10.3390/ph15030294

Abstract

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.

Highlights

Ehrlich ascites carcinoma (EAC)-bearing mice showed a notable reduction in the mean survival time and marked increases in the final body weight, abdominal circumference, ascitic fluid volume, and viable tumor cell count
Our results revealed an increase in the serum CEA level in EAC-bearing mice, which were similar to the findings of Hashem et al [17] and Abd Eldaim et al [19], who reported an elevation in the serum level of CEA in EAC-bearing mice, indicating the tumor metastasis in different organs, comprising ovarian, pancreatic, gastric, and colorectal tumors [20]
The results of the current study showed that the treatment of EAC-bearing mice with Cis induced marked increases in the mean survival time (MST) and ILS%, with significant decreases in the final body weight and abdominal circumference values, ascetic fluid volume, and viable EAC cells count, in addition to the significant reduction in the level of the serum tumor marker, CEA

Summary

Introduction

Despite the wide use of chemotherapeutic drugs for cancer treatment, most of the currently used drugs are nonselective for neoplastic cells, resulting in numerous forms of organ damage [3]

Methods

Results

Discussion

Conclusion