Basic Informations

C.V

Master Title

assessment of immuno genotoxicity of some nanomaterials

Master Abstract

Carbon nanotubes specially MWCNTs have received tremendous attention due to their unique physico chemical properties which enable them to be incorporated in many fields either industrial or medical application, but due to their asbestos like nature a lot of questions around their possible toxicity had been raised. Cinnamon is one of the oldest traditional medicine that has been used for treatment of many disorders due to it is biological activities such as anti-diabetic, anti-oxidant, anti-lepidemic, anti-inflammatory, anti-carcinogenic, anti-coagulant, cardio-protective, neuro-behavioral improvement, anti-microbial, anti-fungal, anti-mycotic, insecticidal and mosquito larvicidal. In attempting to investigate the protective effect of C. burmmani against MWCNTs-induced toxicity, 32 male albino rats (Rattus norvegicus) were used as experimental animals in this study. Animals were weighed weekly during the experimental period to determine the percentage change of body weight. Animals were divided into the following four groups of eight animals each; group (1) is control group in which rats administered distilled water at an equivalent volume of that of the aqueous C. burmanni extract, group (2) rats orally administrated 75 mg / Kg b. wt. of the aqueous extract of C. burmanni daily for four weeks, group (3) including rats exposed to MWCNTs at a dose of 1g/kg b.wt. by adding the dry MWCNTs without any previous treatment into the wood shaving cage litter which gently mixed with litter and changed two times per week for four weeks and group (4) exposed to multi-walled carbon nano-tubes two times per week for four weeks simultaneously with daily oral administration of aqueous extract of C. burmanni at a dose of 75 mg / Kg b. wt. This study includes both in vivo and in vitro investigations. At the end of the in vivo period, animals of all groups were sacrificed under mild diethyl ether anesthesia. Blood samples and tissues were collected. The clear non haemolysed supernatant serum was quickly prepared for analysis of oxidative stress parameters, while formaline- fixed tissue specimens of liver, spleen; kidney and lung were processed and stained with H&E to examine the histological lesions. Another part of the selected tissue (liver) were homogenized in 0.9 % NaCl (10% w/v) for the measurement of oxidative stress markers, while others were refrigerated under -80oC for gene expression determination. The bone marrow smears stained with May-Grunwald- Giemsa stain were prepared and examined for micronucleus detection. Another in vitro study was performed to evaluate the cytotoxic effect of MWCNTs against human cancer cell lines including colorectal cancer cell line (CaCo-2), breast adenocarcinoma cell line (MCF-7) and hepatocellular carcinoma cell line (HepG-2). Results of in vivo study revealed that MWCNTs administration caused significant decrease in the percentage change of body weight, with significant histopathological changes in liver, spleen, kidney and lung. In liver, hepatocytes showed hydropic degeneration, focal necrosis with inflammatory cells infiltration, sinusoidal leukocytosis, vacuolar degeneration and congestion of central vein. However, Spleenocytes showed mitotic figures of the lymphocytes, extra medullary megakaryocytes and slight lymphocytic necrosis. Moreover, histopathological examination of kidney revealed the presence of proteinaceous material in the lumen of renal tubules, vacuolation, congestion of glomerular tufts and peri-vascular oedema, while, lung sections of MWCNTs-intoxicated rats showed peri-vasculitis, interstitial pneumonia, pulmonaryhaemorrhage and focal aggregation of inflammatory cells such as lymphocytes, macrophages, foamy macrophages and mononuclear cells. Moreover, MWCNTs revealed great cytotoxic effect on bone marrow via increasing the number of micronuclei in poly-chromatic erythrocytes. In addition, MWCNTs exposure caused significant elevation of hepatic lipid peroxidation concentration, total thiol content and catalase activity with significant reduction in glutathione content and the activity of super-oxide dismutase, glutathione peroxidase and glutahione-S-transeferase. But, hepatic nitrite content doesn’t significantly affected by MWCNTs exposure. For Serum oxidative stress markers, MWCNTs exposure caused significant elevation in nitrite content concomitant with significant decrease in glutathione and total thiol contents and glutathione-S-transeferase activity. Also, the mRNA expression rate of pro-inflammatory cytokines (IL-1B, IL-6, TNF-a and COX-1) was significantly up regulated in MWCNTs-intoxicated rats. Treatment of MWCNTs- intoxicated rats with aqueous C. burmanni extract showed great amelioration of most histological lesions in tested organs (liver, spleen, kidney and lung) with significant reduction the number of micronuclei in poly-chromatic erythrocytes. Moreover, aqueous C. burmanni extract caused significant reduction in the hepatic content of LPO and total thiol with significant elevation in the activity of SOD, CAT and GPX. However, GSH content and GST activity showed no significant difference. In addition, serum nitrite content was significantly decreased with significant increase in serum GSH and total thiol contents and GST activity. The ameliorative effect of aqueous C. burmanni extract was also recorded in hepatic mRNA expression rate of IL-6, IL-1B, COX-1and TNF-a where their rates were markedly down regulated. On the other hand, in virto studies of MWCNTs on different human cancer cell lines (CaCo-2, MCF-7 and HepG-2) demonstrated significant cytotoxic anti-proliferative activity of MWCNTs where the survival fraction was significantly decreased as the concentration increased. The IC50 for MWCNTs against all tested cell lines were reached recording 376±0.17 for CaCo-2, 196±0.32 for MCF-7 and 187 ± 0.25 for HepG-2.

PHD Title

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PHD Abstract

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