Investigating the Synergistic Effects of Aspartic Acid and Tocopherol on Cytotoxicity and Oxidative Stress Caused by Etoposide on Hepg2 Cell Line by MTT and ROS Methods

Mahboube Rahmati Kukandeh; Maryam  Tangestanizadeh; Hourolein  Arab; Elahe  Gharehkhani; Mohammad  Shokrzadeh

doi:10.18502/ssu.v33i10.20777

Mahboube Rahmati Kukandeh Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
Maryam Tangestanizadeh Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran
Hourolein Arab Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
Elahe Gharehkhani Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
Mohammad Shokrzadeh Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

DOI: https://doi.org/10.18502/ssu.v33i10.20777

Keywords: Aspartic acid, Alpha-tocopherol, Oxidative stress, MTT assay.

Abstract

Introduction: Liver cancer ranks among the deadliest cancers globally. Etoposide, a chemotherapeutic agent frequently utilized in treatment, inhibits topoisomerase II, leading to cell cycle arrest and apoptosis induction. Nonetheless, etoposide generates reactive oxygen species (ROS), resulting in oxidative stress and cellular damage. This study aimed to investigate the combined effects of two antioxidant compounds, alpha-tocopherol and aspartic acid, on cytotoxicity and oxidative stress by etoposide in the HepG2 cell line.

Methods: HepG2 cells were pre-exposed to various concentrations of alpha-tocopherol and aspartic acid (10, 25, 50, 100, 200, and 400 µM). Following pretreatment, cytotoxicity was induced using etoposide at its IC50 concentration (7.08 µM). Subsequently, lipid peroxidation, ROS concentrations, and cell viability parameters were measured.

Results: Based on cell viability measurements and oxidative stress tests, the combination of alpha-tocopherol and aspartic acid with etoposide enhanced cell survival across all tested concentrations. Additionally, they reduced MDA and ROS concentrations.

Conclusion: The findings of this study indicate that alpha-tocopherol and aspartic acid can mitigate the cytotoxic effects of etoposide and provide a protective role by enhancing the cellular antioxidant defense. These results highlight the potential use of this combination as a complementary therapeutic strategy in liver cancer treatment.