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

**Authors:** Nahed Saleh, Tamer Allam, Reda M. S. Korany, Abdelfattah M. Abdelfattah, Ahmed M. Omran, Mabrouk Attia Abd Eldaim, Nermeen Borai El-Borai

PMC · DOI: 10.1038/s41598-025-02442-9 · 2025-06-27

## TL;DR

Hesperidin enhances cisplatin's effectiveness against liver damage caused by Ehrlich ascites carcinoma in mice while reducing cisplatin's side effects.

## Contribution

Hesperidin is shown to improve cisplatin's antitumor effects and reduce its hepatotoxic side effects in EAC-bearing mice.

## Key findings

- Hesperidin reversed EAC-induced liver damage and improved serum and liver biomarkers.
- Hesperidin reduced cisplatin-mediated hepatic toxicity in EAC-bearing mice.
- Hesperidin showed potential as a phytochemical to enhance chemotherapy efficacy and safety.

## 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.

## Linked entities

- **Proteins:** Mki67 (antigen identified by monoclonal antibody Ki 67), Casp3 (caspase 3)
- **Chemicals:** hesperidin (PubChem CID 10621), cisplatin (PubChem CID 5460033), malondialdehyde (PubChem CID 10964), glutathione (PubChem CID 124886)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Lipg (lipase G, endothelial type) [NCBI Gene 16891] {aka 3110013K01Rik, EL, lipase, mEDL}, Alb (albumin) [NCBI Gene 11657] {aka Alb-1, Alb1, BCL001, BCL002, BPL001}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, Afp (alpha fetoprotein) [NCBI Gene 11576], Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345] {aka D630048A14Rik, Ki-67, Ki67}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}
- **Diseases:** hepatic (MESH:D056486), EAC (MESH:D002286), cytotoxic (MESH:D064420)
- **Chemicals:** Cis (MESH:D002945), glutathione (MESH:D005978), malondialdehyde (MESH:D008315), Hesp (MESH:D006569)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** EAC — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_3873)

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12205065/full.md

---
Source: https://tomesphere.com/paper/PMC12205065