Hesperidin exacerbates the therapeutic potency of cisplatin against hepatocytotoxicity of Ehrlich ascites carcinoma in mice

Abstract The present research was set out to delineate the protective and therapeutic potency of hesperidin (Hesp) versus cisplatin (Cis) against the deleterious consequences of Ehrlich ascites carcinoma (EAC) on the liver and the prospective mitigative effect of Hesp against Cis-mediated hepatotoxi...

Full description

Saved in:
Bibliographic Details
Main Authors: Nahed Saleh, Tamer Allam, Reda M. S. Korany, Abdelfattah M. Abdelfattah, Ahmed M. Omran, Mabrouk Attia Abd Eldaim, Nermeen Borai El-Borai
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-025-02442-9
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849420501276950528
author Nahed Saleh
Tamer Allam
Reda M. S. Korany
Abdelfattah M. Abdelfattah
Ahmed M. Omran
Mabrouk Attia Abd Eldaim
Nermeen Borai El-Borai
author_facet Nahed Saleh
Tamer Allam
Reda M. S. Korany
Abdelfattah M. Abdelfattah
Ahmed M. Omran
Mabrouk Attia Abd Eldaim
Nermeen Borai El-Borai
author_sort Nahed Saleh
collection DOAJ
description Abstract The present research was set out to delineate the protective and therapeutic potency of hesperidin (Hesp) versus cisplatin (Cis) against the deleterious consequences of Ehrlich ascites carcinoma (EAC) on the liver and the prospective mitigative effect of Hesp against Cis-mediated hepatotoxic side-effects. A total of 70 female mice were randomly assigned into control, Hesp, EAC, Hesp-protected, Hesp-treated, Cis-treated, and Cis + Hesp-treated groups. Mice inoculated with EAC cells exhibited significant reductions in the serum total protein and albumin levels, along with significant elevations of the serum aminotransferases, lactate dehydrogenase, amylase, and lipase activities, and alpha-fetoprotein level. A significant increment in malondialdehyde level concomitantly with significant declines in reduced glutathione concentration and catalase activity were also observed in the liver of EAC-bearing mice. Additionally, marked hepatic pathological changes as well as a strong Ki-67 expression and a weak caspase-3 expression in the neoplastic cells infiltrating hepatocytes were observed. In contrast, the administration of Hesp and/or Cis to the EAC-bearing mice reversed, to varying degrees, the cytotoxic effects of EAC. Besides, Hesp minimized the harmful hepatic chemotherapeutic side-effects of Cis. Overall, Hesp could be a promising phytochemical against EAC-induced cytotoxicity with its potential to improve the antitumor efficacy of chemotherapeutic drugs and minimize their hepatic adverse side-effects.
format Article
id doaj-art-4e5057e69a1149d68e93f9fa9543ca66
institution Kabale University
issn 2045-2322
language English
publishDate 2025-06-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj-art-4e5057e69a1149d68e93f9fa9543ca662025-08-20T03:31:44ZengNature PortfolioScientific Reports2045-23222025-06-0115111310.1038/s41598-025-02442-9Hesperidin exacerbates the therapeutic potency of cisplatin against hepatocytotoxicity of Ehrlich ascites carcinoma in miceNahed Saleh0Tamer Allam1Reda M. S. Korany2Abdelfattah M. Abdelfattah3Ahmed M. Omran4Mabrouk Attia Abd Eldaim5Nermeen Borai El-Borai6Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Sadat CityDepartment of Clinical Pathology, Faculty of Veterinary Medicine, University of Sadat CityDepartment of Pathology, Faculty of Veterinary Medicine, Cairo UniversityDepartment of Clinical Pathology, Faculty of Veterinary Medicine, University of Sadat CityDepartment of Clinical Pathology, Faculty of Veterinary Medicine, University of Sadat CityDepartment of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Menoufia UniversityDepartment of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, University of Sadat CityAbstract The present research was set out to delineate the protective and therapeutic potency of hesperidin (Hesp) versus cisplatin (Cis) against the deleterious consequences of Ehrlich ascites carcinoma (EAC) on the liver and the prospective mitigative effect of Hesp against Cis-mediated hepatotoxic side-effects. A total of 70 female mice were randomly assigned into control, Hesp, EAC, Hesp-protected, Hesp-treated, Cis-treated, and Cis + Hesp-treated groups. Mice inoculated with EAC cells exhibited significant reductions in the serum total protein and albumin levels, along with significant elevations of the serum aminotransferases, lactate dehydrogenase, amylase, and lipase activities, and alpha-fetoprotein level. A significant increment in malondialdehyde level concomitantly with significant declines in reduced glutathione concentration and catalase activity were also observed in the liver of EAC-bearing mice. Additionally, marked hepatic pathological changes as well as a strong Ki-67 expression and a weak caspase-3 expression in the neoplastic cells infiltrating hepatocytes were observed. In contrast, the administration of Hesp and/or Cis to the EAC-bearing mice reversed, to varying degrees, the cytotoxic effects of EAC. Besides, Hesp minimized the harmful hepatic chemotherapeutic side-effects of Cis. Overall, Hesp could be a promising phytochemical against EAC-induced cytotoxicity with its potential to improve the antitumor efficacy of chemotherapeutic drugs and minimize their hepatic adverse side-effects.https://doi.org/10.1038/s41598-025-02442-9CisplatinEhrlich ascites carcinomaHesperidinAlpha fetoproteinCaspase-3Ki-67
spellingShingle Nahed Saleh
Tamer Allam
Reda M. S. Korany
Abdelfattah M. Abdelfattah
Ahmed M. Omran
Mabrouk Attia Abd Eldaim
Nermeen Borai El-Borai
Hesperidin exacerbates the therapeutic potency of cisplatin against hepatocytotoxicity of Ehrlich ascites carcinoma in mice
Scientific Reports
Cisplatin
Ehrlich ascites carcinoma
Hesperidin
Alpha fetoprotein
Caspase-3
Ki-67
title Hesperidin exacerbates the therapeutic potency of cisplatin against hepatocytotoxicity of Ehrlich ascites carcinoma in mice
title_full Hesperidin exacerbates the therapeutic potency of cisplatin against hepatocytotoxicity of Ehrlich ascites carcinoma in mice
title_fullStr Hesperidin exacerbates the therapeutic potency of cisplatin against hepatocytotoxicity of Ehrlich ascites carcinoma in mice
title_full_unstemmed Hesperidin exacerbates the therapeutic potency of cisplatin against hepatocytotoxicity of Ehrlich ascites carcinoma in mice
title_short Hesperidin exacerbates the therapeutic potency of cisplatin against hepatocytotoxicity of Ehrlich ascites carcinoma in mice
title_sort hesperidin exacerbates the therapeutic potency of cisplatin against hepatocytotoxicity of ehrlich ascites carcinoma in mice
topic Cisplatin
Ehrlich ascites carcinoma
Hesperidin
Alpha fetoprotein
Caspase-3
Ki-67
url https://doi.org/10.1038/s41598-025-02442-9
work_keys_str_mv AT nahedsaleh hesperidinexacerbatesthetherapeuticpotencyofcisplatinagainsthepatocytotoxicityofehrlichascitescarcinomainmice
AT tamerallam hesperidinexacerbatesthetherapeuticpotencyofcisplatinagainsthepatocytotoxicityofehrlichascitescarcinomainmice
AT redamskorany hesperidinexacerbatesthetherapeuticpotencyofcisplatinagainsthepatocytotoxicityofehrlichascitescarcinomainmice
AT abdelfattahmabdelfattah hesperidinexacerbatesthetherapeuticpotencyofcisplatinagainsthepatocytotoxicityofehrlichascitescarcinomainmice
AT ahmedmomran hesperidinexacerbatesthetherapeuticpotencyofcisplatinagainsthepatocytotoxicityofehrlichascitescarcinomainmice
AT mabroukattiaabdeldaim hesperidinexacerbatesthetherapeuticpotencyofcisplatinagainsthepatocytotoxicityofehrlichascitescarcinomainmice
AT nermeenboraielborai hesperidinexacerbatesthetherapeuticpotencyofcisplatinagainsthepatocytotoxicityofehrlichascitescarcinomainmice