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Abstract The aim of this work was to study the different side effects appeared in rats after exposure to etoposide and the protective potential of ginger (Zingiber officinale) oral administration against toxicity of etoposide. : Material used in the work 1- Etoposide (1mg/kg b.wt.): it was used as an anticancer drug and served as a toxicant. 2- Ginger volatile oil (Zingiber officinale) (75mg/kg b.wt., 150mg/kg b.wt.): is a medicinal plant material and administered as a protective agent. The present study was carried out using 60 adult male albino rats (Rattus norvegicus) weighting 130±10 g. In this study, the major experiments are planned as - : following 1- Choice of etoposide (1mg/kg b.wt.) period of treatment and selection was carried out according to maximum damage occurred in DNA in liver and spleen tissues. 2-The protective role of Zingiber officinale volatile oil (75mg/kg b.wt., 150mg/kg b.wt.) against DNA damage induced by etoposide in liver and spleen after 21 days. Summary 109 3- Determination of the protective potential of ginger oil against damage induced by etoposide in liver and spleen tissue after 21 days of treatment. 4- Determination of DNA damaged cells percentage by alkaline single cell gel electrophoresis (SCGE)/comet assay and the protective potential of Zingiber officinale (ginger) volatile oil against damage induced by etoposide in peripheral blood leukocytes after 72 hours of treatment. 5- Determination of chromosomal aberrations in bone marrow, these aberrations include chromatid deletion, fragmentation, centromeric attenuation, end to end association, centric fusion, break, gap and ring chromosome after 72 hours of treatment. 6- Determination of mitotic index in bone marrow after 72 hours of treatment. 7-Determination of the oxidative status in liver and spleen tissue as (SOD, MDA, CAT, NO and GSH) after 21days of treatment. The findings of this study are summariezed as follows: Determination of total genomic DNA damage and apoptosis detection in liver and spleen treated with etoposide to specify the treatment period which cause the maximum damage. The results showed that etoposide induced the maximum DNA damage (apoptosis) after 21 days of treatment. The protective role of Zingiber officinale volatile oil against genomic DNA damage induced by etoposide in liver and spleen after 21 day of treatment. The obtained results showed that Zingiber officinale can exert preventive effects on the development of genotoxic potential produced due to the administration of etoposide at the level of DNA damage determination by agarose gel electrophoresis. Summary 110 Alkaline single gel electrophoresis (SCGE)/comet assay for leukocytes after 72 hours of treatment. The results of comet assay technique revealed that, administration of Zingiber officinale oil showed significant improvement by the reduction in DNA damaged cells when compared with etoposide treatment groups. Determination of chromosomal aberrations after 72 hours of treatment. The obtained results showed that Zingiber officinale oil can decrease the percentage of chromosomal aberrations when compared with etoposide treatment groups. Determination of mitotic index after 72 hours of treatment. The results showed that treatment with etoposide decreased the mitotic index in contrast the treatment with ginger oil which improved the percentage of mitotic index. Examination of Biochemical assay after 21 days of treatment. Animal treated with etoposide alone showed increase in the level of MDA and NO but decrease in the level of (CAT, SOD and GSH) while animals protected with ginger oil shows decrease in the level of MDA and NO but increase in the level of (CAT, SOD and GSH) in liver and spleen tissue. Hense, all these results together showed that etoposide treatment could induce cytotoxicity and genotoxicity but these side effects also can be reduced or even prevented in some cases by the protective agents of plant origin such as Zingiber officinale oil which has been used in this study. |