Authored by Fawiza Zakaria ELAblack*
Abstract
Background: Azoles has been used traditionally for many centuries. Some impressive therapeutic qualities have been discovered.
Aim: Our study aims to investigate in vivo antitumor, and antioxidant activities of Ethanolic Azoles. Also, to study the side effects of Azoles on different organs (Liver/ Kidney).
Materials & Methods: We assessed the effect of Azoles on life span prolongation and on the levels of malondialdehyde (MDA), nitric oxide (NO), Catalase, glutathione peroxidase (GPx), Caspase-3, and Cytochrome c. Also, our study estimated their effect on Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Total Protein (T.P), Albumin (Alb), bilirubin, urea and creatinine.
Results: Azoles showed great increase in life span. Also, they showed a significant decrease in malondialdehyde and nitric oxide and an increase in catalase, glutathione peroxidase, caspase-3 activities, and cytochrome c concentration. Hence, it may be possible that Azoles decrease lipid peroxidation level due to their antioxidant effect and enhance apoptosis process. Azoles showed no side effects on liver and kidney. Also, they showed a significant protection for both liver and kidney histopathologically
Keywords: Antitumor activity; Erlich ascites carcinoma; Novel azoles; Triazole derivatives; Benzimidazole; Swiss albino mice
Introduction
Benzimidazole being an isostere of purine based nucleic acid and an important scaffold in various biologically active molecules is widely explored for development of anticancer agents [1]. The versatility of new generation benzimidazole would represent a fruitful pharmacophore for further development of better medicinal agents [2]. Thus, benzimidazole-derived moieties’ introduction to the drug design may enhance the biological activities. As, triazoles are safe for most patients; their use in medically complex cases can be complicated further by dose-limiting toxicities and pharmacokinetic drug-drug interactions Cancer is a severe metabolic syndrome and is one of the leading causes of death regardless of developments in the tools of disease diagnosis, treatment and prevention measures [3,4]. Cancer development and progression, programmed cell death (apoptosis) and the genes regulating this process involved in tissue and organ homeostasis and loss of the apoptotic process is often associated with tumour expansion, Alterations in the expression of proteins involved in intracellular apoptotic pathways are a potential cause of neoplastic expansion, so the earliest and most specific tumour markers are usually detectable at the intracellular level [5]. When exposure the cells to the external damage stimuli, they activate the regulation of expression of P53 and Bcl-2 genes. P53 tumor suppressor protein acts as a protector of genomic activity by inducing either cell cycle arrest (at G1 and/or G2 phase) or apoptosis. Bc1-2 gene is an anti-apoptotic protein, participate in the p53 apoptotic pathway and the equilibrium between those positively and negatively regula-tory proteins is essential for the susceptibility to apoptosis. A high level of Bcl-2 expression prevents cells from apoptosis caused by cytotoxic factors or cellular stress [6]. Ehrlich ascites carcinoma (EAC) considered as an experimental tumor modeling. EAC is referred to as an undifferentiayrd carcinoma and is originally hyper diploid, has high transplantable capability, no-regresion, rapid proliferation, shorter life span, 100% malignanc, and resembles human tumors which are the most sensitive to chemotherapy due to they are undifferentiated and have a rapid growth rate [7] Development and identification of compounds capable of killing transformed or cancer cells, without being toxic, is of utmost importance, and has gained the increasing interest of scientists worldwide [8]. The major side effect associated with various anticancer or anti-proliferative agents is cytotoxicity towards normal cells due to lack of selectivity for the abnormal cells. Therefore, search on anticancer agent has been in continuum since many years [9]. Cisplatin is one of the most compelling chemotherapy drugs that are widely used for cancer. It was the first FDA-approved platinum compound for cancer treatment in 1978 [10]. Common side effects for using Cisplatin include bone marrow suppression, hearing problems, kidney problems, and vomiting. Other serious side effects include numbness, trouble walking, allergic reactions, electrolyte problems, and heart disease. Use during pregnancy is known to harm the baby [11]. However, the severe side effects and resistance by the cancer cells confine their clinical application widely. To curb increasing resistance and the unbearable cost of treatment, it is a necessity to design potential alternatives [12]. Benzimidazole derivatives have demonstrated as potential new therapeutics for the treatment of cancer in vitro and in vivo [13]. The present study was carried out to investigate the anti-tumor activity of newly synthesised azoles in comparison with cisplatin against Ehrlich ascites carcinoma in Swiss albino mice.
Materials and Methods
Experimental animals
Studies were carried out using a total of 75 male Swiss albino mice weighting 22- 25 g obtained from Animal House of National Research Center, Giza, Egypt. The experimental animals were housed 15 per cage in a room with 65% humidity, 12:12 h light: dark cycle at ambient temperature of 20 ± 1 _C. Standard diet, commercial feed pellets and tap water were freely available (Figure 1).
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