Biochemical and pathophysiological improvements in rats with thioacetamide induced-hepatocellular carcinoma using aspirin plus vitamin C

Sep 24, 2026

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death, motivating safer and more effective treatments than standard chemotherapeutics. This study evaluated the anti-HCC activity of a synergistic combination of aspirin and vitamin C compared with doxorubicin in HCC-bearing rats and HepG-2 cells. In vitro assays measured IC50 and selectivity index, while in vivo dosing assessed biochemical markers, inflammatory cytokines, apoptotic proteins, and histopathology. The combination showed stronger improvements and favorable safety.

LanguageEnglish

CategoryResearch & Report

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Pages10

Reading Time25 min

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Abstract

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Introduction

El Sadda etal. BMC Cancer (2023) 23:175 [https://doi.org/10.1186/s12885-023-10644-5](https://doi.org/10.1186/s12885-023-10644-5) BMC Cancer RESEARCH Open Access Biochemical and pathophysiological improvements in rats with thioacetamide induced-hepatocellular carcinoma using aspirin plus vitamin C Rana R. El Sadda1, Zahraa R. Elshahawy 1,2 and Entsar A. Saad 1* Abstract Background Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, so we should be concerned and look for effective/less-harmful treatments than chemotherapeutics already clinically in application. Aspirin works well ’’in conjunction’’ with other therapies for HCC since aspirin can boost the sensitivity of anti-cancer activity. Vitamin C also was shown to have antitumor effects. In this study, we examined the anti-HCC activities of synergistic combination (aspirin and vitamin C) vs. doxorubicin on HCC-bearing rats and hepatocellular carcinoma (HepG-2) cells. Methods In vitro, we evaluated IC50 and selectivity index (SI) using HepG-2 and human lung fibroblast (WI-38) cell lines. In vivo, four rat groups were used: Normal, HCC (intraperitoneally (i. p.) administered 200 mg thioacetamide/kg/ twice a week), HCC + DOXO (HCC-bearing rats i. p. administered 0.72 mg doxorubicin (DOXO)/rat/once a week), and HCC + Aspirin +Vit. C (i. p. administered vitamin C (Vit. C) 4 g/kg/day after day concomitant with aspirin 60 mg/kg/ orally day after day) . We evaluated biochemical factors [aminotransferases (ALT and AST), albumin, and bilirubin (TBIL) spectrophotometrically, caspase 8 (CASP8), p53, Bcl2 associated X protein (BAX), caspase 3 (CASP3), alpha-fetoprotein (AFP), cancer antigen 19.9 (CA19 . 9), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) using ELISA], and liver histopathologically. Results HCC induction was accompanied by significant time-dependent elevations in all measured biochemical parameters except the p53 level significantly declined. Liver tissue architecture organization appeared disturbed with cellular infiltration, trabeculae, fibrosis, and neovascularization. Following drug medication, all biochemical levels significantly reversed toward normal, with fewer signs of carcinogenicity in liver tissues. Compared to doxorubicin, aspirin & vitamin C therapy ameliorations were more appreciated. In vitro, combination therapy (aspirin & vitamin C) exhibited potent cytotoxicity (HepG-2 IC50 of 17.41 ± 1.4 µg/mL) and more excellent safety with a SI of 3.663. Conclusions Based on our results, aspirin plus vitamin C can be considered reliable, accessible, and efficient synergistic anti-HCC medication. Keywords Caspase, Synergistic, CA19 . 9, AFP, BAX, p53, TNF-α *Correspondence: Entsar A. Saad [entsarsaad@gmail.com](entsarsaad@gmail.com); [entsarsaad@du.edu.eg](entsarsaad@du.edu.eg) 1 Chemistry Department, Faculty of Science, Damietta University, Damietta 34517, Egypt 2 Gastroenterology Surgical Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain

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What major biochemical and tissue changes were observed after HCC induction and treatment?

HCC induction increased multiple biochemical parameters and disrupted liver architecture, while post-treatment reversed biochemical levels toward normal with fewer carcinogenic signs; aspirin plus vitamin C showed more pronounced improvements than doxorubicin.

Sep 24, 2026

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