الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 234 |  |  |
| | | from | 234 | | |
Abstract
The lung is a vital organ that fulfils a vital function, process of gas exchange called respiration (or breathing). In respiration, oxygen from incoming air enters the blood, and carbon dioxide, a waste gas from the metabolism, leaves the blood.
Lung cancer remains the leading cause of cancer mortality worldwide. Across Europe in 2018, there were an estimated 388,000 lung cancer-related deaths, which was higher than those related to colorectal cancer and breast cancer combined.
Urethane is a potent lung carcinogen present in tobacco leaves and tobacco smoke. Urethane is enzymatically metabolized into vinyl carbamate epoxide and N-hydroxylamine epoxide, which generate oxidative stress in cells milieu by generating reactive oxygen (O2 −) and nitrogen species (NO) as well as formation of DNA adducts.
These free radicals cause oxidation and depurination of DNA. Excess of free radicals generations causes oxidative damage to cellular components including DNA leading to constitutive activation of signaling pathway, promoting and initiating a cascade of lipid per-oxidation, and protein oxidation which elicit inflammation-driven carcinogenesis.
Cisplatin was recognized as an anticancer drug and was followed by extensive researches and thus, many platinum-based complexes were synthesized and tested as anti-cancer agents.
Despite of good clinical success of cisplatin, it lacks tumor tissue selectivity leading to some severe side effects.
Routine therapeutic approaches in cancer suppression such as radiation therapy, chemotherapy, surgery, etc. due to their undesirable therapeutic outputs, including low efficiency in cancer inhibition, non-targeted drug delivery, nonselective distribution, and enormous side effects, have been indicated inefficient potency in cancer therapy or at least its growth inhibition. As a result, the development of novel and practical therapeutic methods such as nanoparticle-based drug delivery systems can be outstandingly beneficial in cancer suppression
Advances in nanotechnology and growing needs in biomedical applications have driven the development of multifunctional nanoparticles.
Nanotechnology is defined as the intentional design, characterization, production, and applications of materials, structures, devices and systems by controlling their size and shape in the nanoscale range (1 to 100 nm).
Nanomedicine is the medical application of nanotechnology. The basic point to use drug delivery is based upon three facts: efficient encapsulation of the drugs, successful delivery of these drugs to the targeted region of the body and successful release of that drug there.
Cancer nanotechnology, a discipline at the intersection of engineering and the physical sciences with cancer biology and clinical practice, has the potential to radically alter disease outcomes.
Functional nanoparticles have evoked keen interest in recent decades owing to their size- and shape dependent optical, catalytic and therapeutic properties. These properties can overcome the limits of conventional medicine, including lack of selectivity, poor pharmacokinetics and undesirable side effects.
The present study was conducted to evaluate the efficiency of biologically synthesized platinum nanoparticles in treatment of lung carcinoma compared to cisplatin both in vitro and in vivo studies. The obtained nanoparticles were characterized by means of transmission electron microscopy (TEM), X ray diffraction and Fourier transform infrared (FTIR) spectroscopy.
The cytotoxic-effects and the biological activity of platinum nanoparticles and cisplatin as antitumor agents were examined in vitro against human lung carcinoma cell line (A-549) using crystal violet cytotoxicity assay. Results showed potent effect of CHNM nanocomposites have nearly the same potent effect of cisplatin in a dose dependent manner, where increasing concentration of CHNM resulted in increased percentage of dead cells.
For in vivo experiments a total number of 72 adult male wistar rats (100-120 g) divided into 6 equal groups were used: group (1) Control group
group (2) Cisplatin: Animals were injected with cisplatin 10% of LD50 (0.64mg/kg body weight/day).
group (3) CHNM: Animals were injected intra-peritoneally with Nanocomposites (200 mg/kg b.w./day).
group (4) Urethane: Animals were injected with urethan in a dose of 1 g/kg b.w., 3consecutive injections with 48 hr gab.
group (5) Urethane + cisplatin: Rats received urethane as in group 4 then treated with cisplatin
group (6) Urethane + CHNM: Animals were injected with urethan as in group 4 then treated with.
At the end of the experiment all animals were sacrificed, lung tissues were taken for the assessment of different parameters.
The Evaluation of PI3K/AKT/mTOR pathway was measured in lung tissue homogenate. In addition to evaluation of antiapoptic B-cell lymphoma 2 (BCL-2) and apoptic caspase 9 factors. Histopathological examination for lung tissue was also performed.
The results of the present study can be summarized as follows:
1- Injection of urethane in male Wistar rats induced significant
changes in lung tissue including:
a. A significant upregulation of BCl-2 and K-ras genes compared to normal group.
b. A significant decrease in the expression level of PTEN protein in lung tissues, in addition to significant decrease in the expression level of dephosphorylated form of mTOR protein in lung tissues were reported when compared to control group.
c. In addition, the concentration levels of PI3K and AKT proteins remarkably increased, while that of CAS-9 remarkably decreased.
d. Histopathological studies showed anaplastic changes of pneumocytes type ІІ inside the alveoli in addition to anaplastic changes of nucleus of pneumocytes type ІІ in inter alveolar septa
2- Treatment of lung cancer induced rats with cisplatin or CHNM revealed remarkable amelioration in all the previous measurements
3- Histopathological studies showed improvement following CHNM and cisplatin treatment where all sections showed nearly normal architecture.
from the previous results it can be concluded that CHNM nanomaterial is potent drug in treatment of lung cancer induced by urethane in rats, suggesting that CHNM can serve as good therapeutic agent for the treatment of lung cancer which should attract further studies.