N-Butylpyridoquinoxaline 1,4-dioxide (NBPQD) as a new potent for tumor imaging and therapy

Salem A Habib,Mohamed A Abd-Eldaye,Ismail T Ibrahim,Mamdouh M El-Sheshtawey,Heba M Waly

doi:10.4236/ns.2012.412136

Salem A Habib, Mohamed A Abd-Eldaye + Show 3 more

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https://doi.org/10.4236/ns.2012.412136

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Journal: Natural science	Publication Date: Jan 1, 2012
Citations: 16	License type: CC BY 4.0

Affiliation: Damietta University, Mansoura University

Abstract

The development of new and effective antitumor agents is one of the main goals of medicinal and biochemical research at present. The present study is concerned with the evaluation of the previously synthesized N-Butylpyridoquinoxaline 1,4-dioxide (NBPQD) as an antitumor agent against Ehrlich ascites carcinoma (EAC). The first part of the study (tumor imaging) was to investigate the biodistribution of NBPQD in the organs of EAC-bearing mice using iodine-125 isotope stressing on its distribution in the main organs (stomach, liver, spleen, kidney) in addition to blood and ascetic fluid. The second part was the assessment of the antitumor activity of NBPQD by estimating the tumor volume and the contents of total protein, total lipid, DNA and RNA in liver tissues. In addition, liver function tests and the redox status were assessed. Tumor volume and DNA, RNA, urea and malondialdehyde (MDA) levels and the liver enzymes activity were highly significantly increased (P < 0.001) in untreated EAC-bearing mice compared to control. However, total lipid and total protein in liver tissues in addition to serum albumin, glucose, reduced glutathione (GSH) as well as activities of glutathione reductase (GSH-R) and superoxide dismutase (SOD) all were highly significantly decreased in untreated EAC-bearing mice compared to controls. All these decreased parameters were highly significantly restored to their normal levels in NBPQD treated mice compared to the untreated EAC-bearing mice. The survival time of the NBPQD treated mice was longer than that of the untreated ones. It is thus, evident that NBPQD had a remarkable antitumor activity against EAC in Swiss albino mice.

Highlights

Cancer is one of the major causes of death
Oxidative stress is defined as a disturbance in the equilibrium between free radicals (FR), reactive oxygen species (ROS), and endogenous antioxidant defense mechanisms, or more it is a disturbance in oxidantantioxidant states, favoring the oxidant environment [4]
Superoxide anion ( O2 ) can be dismutated to hydrogen peroxide (H2O2) by two enzymes, namely copper-zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD), that are present in the mitochondrial matrix and in the intermembrane space, respectively [5]

Summary

Introduction

Reactive oxygen species (ROS) increase the rate of mutagenicity, which leads to DNA damage and chromosomal instability, thereby potentiating cancer progression [1,2]. ROS may promote cell survival and proliferation, contributing to cancer development. The abnormal regulation of ROS has a role in pathological conditions, including inflammation, atherosclerosis, angiogenesis and aging [3]. Oxidative stress is defined as a disturbance in the equilibrium between free radicals (FR), reactive oxygen species (ROS), and endogenous antioxidant defense mechanisms, or more it is a disturbance in oxidantantioxidant states, favoring the oxidant environment [4]. Cells have evolved several antioxidant defenses, including repair and detoxifying enzymes, and small scavenger molecules, such as glutathione. The intracellular ROS-scavenging system includes superoxide dismutases (SOD), glutathione peroxidase (GPx), peroxiredoxins (PRDXs), glutaredoxins, thioredoxins (TRXs), and catalases. Superoxide anion ( O2 ) can be dismutated to hydrogen peroxide (H2O2) by two enzymes, namely copper-zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD), that are present in the mitochondrial matrix and in the intermembrane space, respectively [5]

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