Research Articles

2018  |  Vol: 3(5)  |  Issue: 5 (September- October) | https://doi.org/10.31024/apj.2018.3.5.5
Genoprotective effects of Amifostine against Mitoxantrone induced toxicity in HepG2 cells, detected via the Comet assay

Mohammad Shokrzadeh, Nasrin Ghassemi-Barghi*

Faculty of pharmacy, Department of Pharmacology and Toxicology, Pharmaceutical Research Committee, Mazandaran University of Medical Sciences, Sari, Iran

*Address for Corresponding Author

Nasrin Ghassemi-Barghi, 

Department of Toxicology and Pharmacology,

Faculty of Pharmacy Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran

Abstract

Background: Mitoxantrone is involved in secondary malignancy due to its genotoxic potential. It can cause single and double strand breaks induction and inhibition of DNA synthesis, increase in reactive oxygen species (ROS) production and transient depletion of intracellular glutathione. Amifostine is a cytoprotective adjuvant used in cancer chemotherapy and radiotherapy involving DNA-binding chemotherapeutic agents. It has been shown to exert an important cyto-protective effect in many tissues and directly limit cell injury and ROS generation during oxidative stress. Also, amifostine exerts anti-inflammatory and anti-apoptotic effects in several systems. Objective: The aim of this study was to explore whether amifostine protects against mitoxantrone-induced genotoxicity. Materials and Methods: For this purpose, cells were incubated with amifostine and mitoxantrone in pre and co-treatment condition and then then genoprotective effects of amifostine have been determined via comet assay. Oxidative stress was measured with intracellular reactive oxygen species and glutathione levels. Results and conclusion: Our results showed that mitoxantrone induced a noticeable genotoxic effects in HepG2 cells (p<0.0001). Amifostine reduced the effects of mitoxantrone significantly (p<0.0001) by reduction of the level of DNA damage via blocking ROS generation, and enhancement of intracellular glutathione levels.

Keywords: Mitoxantrone, Amifostine, genotoxicity, comet assay, reactive oxygen species

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