In vitro genotoxicity and cytotoxicity of a particular combination of pemetrexed and cefixime in human peripheral blood lymphocytes.

Erman Salih Istifli,Mehmet Topaktaş

doi:10.1186/s40064-015-0803-3

Erman Salih Istifli, Mehmet Topaktaş

Open Access

https://doi.org/10.1186/s40064-015-0803-3

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Journal: SpringerPlus	Publication Date: Jan 28, 2015
Citations: 31	License type: CC BY 4.0

Affiliation: Cukurova University

Abstract

This study aims to find the genotoxic and cytotoxic effects of a particular combination of pemetrexed (PMX) and cefixime (CFX) in human peripheral blood lymphocytes. Chromosome aberration (CA), sister chromatid exchange (SCE), and micronucleus (MN) tests were used to assess genotoxicity. Whereas, the cytotoxicity was evaluated by using mitotic index (MI), proliferation index (PI), and nuclear division index (NDI). Our tests were proceeded with concentrations of 12.5 + 450, 25 + 800, 37.5 + 1150, and 50 + 1500 μg/mL of a mixture of PMX and CFX separately for 24 hr and 48 hr.The combination of PMX + CFX did not induce the CA or SCE in human peripheral blood lymphocytes when compared with both the control and the solvent control. MN in human peripheral blood lymphocytes was not significantly increased after treatment with a particular combination of PMX + CFX. However, PMX + CFX significantly decreased the MI, PI and NDI at all concentrations for 24- and 48-hr treatment periods when compared with both controls. Generally, PMX + CFX inhibited cell proliferation more than positive control (MMC) and showed a higher cytotoxic effect than MMC at both treatment periods. These results were compared with individual effects of PMX and CFX. As a result, it was observed that a particular combination of PMX + CFX was not genotoxic. However, the combination synergistically increase cytotoxicity in human peripheral blood lymphocytes.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-015-0803-3) contains supplementary material, which is available to authorized users.

Highlights

In cytotoxic chemotherapy, patients often receive myelosuppressive doses of antineoplastic agents (Voog et al 2000)
Increasing combination concentrations did not cause a significant increase in the percentage of the binuclear cells with micronuclei (MNBN%) for 24- and 48-hr treatment periods (Table 1). %MN was not significantly increased when compared with both the negative and the solvent controls in cells treated with PMX + CFX for 24- and 48-hr treatment periods (Table 1)
Our results showed that the combination of PMX and CFX exerted synergistic cytotoxic activity, but not genotoxicity, in human peripheral blood lymphocytes

Summary

Introduction

Patients often receive myelosuppressive doses of antineoplastic agents (Voog et al 2000). The majority of patients receiving antineoplastic drugs are potential recipients of antibiotics because of significant myelosuppression that makes them susceptible to bacterial infections. It is well-known that drugs regardless of their sequence of administration can interact with each other. The outcome of these interactions can not be predicted based on the individual effect of each drug in their combination. According to Pakulska (1992), benzypenicillin which normally does not demonstrate potential cytotoxic and genotoxic activity (Koseoglu et al 2004), Istifli and Topaktaş SpringerPlus (2015) 4:35 could be at risk for potential antineoplastic-antibiotic interactions during the treatment of bacterial infection

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