الفهرس 
Introduction and Aim of the workOnly 14 pages are availabe for public view
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Abstract
The global efforts have been banded together for synthesizing new anticancer drugs with higher potentiality and lesser side effects aiming to decrease the death rate in cancer patients.
Nanotechnology in the medical field aims to provide a valuable collection of research tools and many effective treatments in the near future as nanoparticles have extraordinary abilities to destroy the cancer cells while preserving the normal ones. In this regard, it considered to be an important key for cancer treatment, the progress in this area improves the control of the disease and its treatment.
Selenium (Se) is an important element in our bodies it plays an important role in protecting against cardiovascular events, boosting the immune system strength, reducing inflammations, reducing the signs of aging and in hormonal balance. Studies have revealed the role of Se to protect against cancer, as it increases the glutathione peroxidase enzyme activity (GPx) and protects against the harmful effect of free radical that cause cancers. It has been shown also that there is a great deal between Se deficiency and the increase in the incidence rate of cancer.
Ionic liquids have also attracted the scientific community’s due to their pharmaceutical properties such as anticancer activities. The anticancer activity and cytotoxicity of phosphonium and ammonium-based ILs have been determined for the first time via American National Cancer Institute’s (NCI’s) in in vitro 60 human tumor cell lines. In general, phosphonium-based ILs were found to be more active and less cytotoxic as compared to ammonium ILs.
The present study was designed to synthesize and evaluate the antitumor efficacy of zinc selenite nanoparticles (ZnSeO3-NPs) in comparison with trihexyl (tetrdecyl) phosphonium ionic liquid (IL) against kidney carcinoma induction in an animal model using diethylinitrosamine (DEN) and ferric nitrilotriacetate (Fe-NTA) as a potent cancer inducer.
The work comprises a series of in vitro and in vivo investigations. The in vitro studies included evaluation of cytotoxic effect of the tested compounds against baby hamster kidney (BHK-21) cell line. The results recorded from in vitro studies showed that the trihexyl (tetrdecyl) phosphonium ionic liquid (IL) was superior in its anticancer potentiality than zinc selenite nanoparticles (ZnSeO3-NPs) where; it recorded lower IC_50 value on BHK-21cell line.
To achieve the goal in vivo, 60 male Wister rats were used and allocated into 6 groups, ten rats for each group as following:
group 1 (Control): Rats in this group were left normal untreated for 5 months, and then they were sacrificed for analysis.
group 2 (ZnSeO3-NPs): Rats in this group were normal rats which were orally administrated with ZnSeO3-NPs 50 mg/kg b.w. calculated according to Akhila et al., (2007) three times a week (each alternate day) during the treatment month, and then they were sacrificed for analysis.
group 3 (IL): Rats in this group were normal rats which were orally administrated with IL 35.5 mg/kg b.w. (Akhila et al., 2007) three times a week (each alternate day) during the treatment month, and then they were sacrificed for analysis.
group 4 (DEN+Fe-NTA): Rats received a single intraperitoneal injection of DEN at a dose level of 200 mg/kg b.w. (Afzal et al., 2013) on the first day and after ten days the carcinogenesis was promoted by Fe-NTA at a dose of 9 mg/kg b.w. (i.p) for 16 weeks (Tamanna and Sarwat, 2006), and then they were sacrificed for analysis.
group 5 (Carcinogen+ZnSeO3-NPs): Rats received carcinogen as mentioned in group 4 for 16 weeks till tumor induction, then treated with ZnSeO3-NPs as described in group 2 for 1 month, and then they were sacrificed for analysis.
group 6 (Carcinogen+IL): Rats received carcinogen as mentioned in group 4 for 16 weeks, then treated with IL as described in group 3 for 1 month, and then they were sacrificed for analysis.
After five months from the beginning of the experiment, animals were sacrificed for the biochemical studies including determination of antioxidant activity in blood and kidney tissue homogenate (GSH, GPx, SOD and CAT), and lipid peroxidation (LPx) level in plasma and kidney tissue homogenate as well as determination of kidney function parameters (creatinine, urea, potassium (K+) and total protein), in addition to determination of tumor markers levels (CEA and LDH), caspase 3 level was estimated in kidney tissue homogenate as well. Parts of kidney tissues were used for histopathological investigations.
The results of the present study can be summarized as follows:
The biochemical studies revealed that rats injected with the carcinogenic compounds showed marked decreasing in antioxidant enzymes as reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) due to over production of reactive oxygen species by the carcinogenic compounds that cause imbalance in antioxidant defense. An elevation in lipid peroxide level (LPx) indicating the damage occurred in lipid membranes during carcinogenic process. An elevation in creatinine, urea, potassium (K+) and total protein due to oxidative stress on the integrity of membranes causing damage to kidney tissues. A marked elevation in carcinoembryonic antigen (CEA) and lactate dehydrogenase (LDH). Also there was a slight increase in the level of caspase 3 in the tissue homogenate.
The histopathological investigations revealed that rats injected with carcinogenic compounds showed congestion in their glomerular tufts associated with degeneration and dysplasia and disfiguration in the lining epithelium of the tubules a great area was replaced by numerous islets of hyperplasia cells.
Adminestration of zinc selenite nanoparticles (ZnSeO3-NPs) or trihexyl (tetrdecyl) phosphonium ionic liquid (IL) revealed an improvement in the antioxidant enzymes such as reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and decreases lipid peroxidation (LPx) level. It revealed an improvement in kidney function parameters as creatinine, urea, potassium (K+), and total protein as well. It showed a marked decrease in tumor markers tests such as carcinoembryonic antigen (CEA) and lactate dehydrogenase (LDH). Also a mrked increase in the level of caspase 3 have been detected in the treated groups.
The histopathological investigations revealed that rats treated with different compounds could repair the kidney structure in comparison with tumor injected rats.
In conclusion, the aforementioned results revealed that both zinc selenite nanoparticles (ZnSeO3-NPs) and trihexyl (tetrdecyl) phosphonium ionic liquid (IL) have a comparable ability against carcinogen which showed by improving the antioxidant system, depletion in lipid peroxidation, repairing kidney structure and function and initiating apoptotic process in kidney tissue during cancer formation. Moreover, the present study proved that zinc selenite nanoparticles (ZnSeO3-NPs) is better than trihexyl (tetrdecyl) phosphonium ionic liquid (IL) in cancer treatment.