الفهرس 
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Abstract
Iron is an essential element that participates in several metabolic activities of cells; though, excess iron is a major cause of iron-induced oxidative stress and several human diseases through the formation of hydroxyl radicals and lipid peroxidation. Likewise, ionizing radiation exposure caused deleterious effects on physiology, metabolism, and behavior in almost all organisms. One of the basic mechanisms of radiation damage is the production of free radicals, leading to the formation of peroxides and oxidative reactive species. These free radicals play a significant role in the human body because they can induce damage to cell structure, damage to DNA, protein oxidation, and lipid peroxidation.
Antioxidants are known to scavenge free radicals, thereby decreasing the degree of such effects. Naringin, a bioflavonoid predominant in grapefruit and other citrus fruits, has been found to scavenge free radicals; therefore it may also reduce radiation and iron overload-induced damage.
So, the present study was performed to detect the modulating effect of naringin (80 mg/kg b.wt.) to overcome the toxic effects of γ-irradiation and iron dextran. The parameters studied in the current study were complete blood picture (CBC) in blood; serum AST, ALT, ALP, total bilirubin, glucose, protein profile (total protein, albumin, globulin, and A/G ratio), cholesterol, triglyceride, high density lipoprotein cholesterol (HDL- C) and low density lipoprotein cholesterol (LDL-C); serum iron, total iron binding capacity (TIBC), transferrin, ferritin and serum urea, creatinine concentrations. Liver and kidney glutathione (GSH) content, superoxide dismutase (SOD), metallothioneins (MTs), lipid peroxidation (LPO), reactive oxygen species (ROS) levels were also investigated. In addition,
levels of some trace elements (Zn, Cu, Mg, Mn, Ca and Fe) in liver and kidney tissues and the correlation between these trace elements with oxidative stress and antioxidant markers as well as between GSH and ferritin were also displayed. Finally, the histopathological examinations were assayed in liver tissue.
Male Swiss albino rats (64 rats) were used, weighing 120-150g, divided into 8 groups, each consists of 8 rats:
group 1: was a normal control group, group 2: consisted of rats subjected to a single dose of whole body γ-irradiation (6.5 Gy), and sacrificed after 7 days of irradiation, group 3: received naringin (NIN) (80 mg/kg b.wt) for 21 successive days by oral gavage, group 4: received NIN for 14 days, then was exposed to γ-radiation (6.5Gy), followed by treatment with NIN 7 days later to be 21 days, group 5: was interaperatonially injected with iron dextran (ID) (50 mg /Kg b. wt.) 3 times per week for 2 weeks, group 6: was administered ID (50 mg/ kg b.wt) (3 times per week) for two weeks and then exposed to γ-irradiation
6.5 Gy and animals were scarified after 7 days, group 7: received NIN daily and ID (3 times per week) for two weeks followed by oral gavage of NIN for another week and group 8: received NIN daily for 2 weeks and ID (3 times per week) for two weeks followed by γ-radiation exposure then was administered with naringin for another week.
The sacrifice of all animals was performed at the end of the experiment and blood, liver and kidney tissues were obtained for determination of different biochemical parameters and histopathological examination.
The results of the present study can be summarized as follows:
1- Exposure to γ-irradiation exhibited a profound elevation of (AST, ALT, ALP), total bilirubin, glucose, serum iron, TIBC, transferrin and ferritin, urea and creatinine levels, lipid profile (CH, TG, LDL-c, HDL-c) abnormalities and an increase in liver (LPO and ROS) were also observed. Noticeable decrease in liver GSH content as well as SOD activity in both liver and kidney, hematological parameters (WBCs, RBCs, Hb) and serum total protein, albumin and A/G ratio were also recorded. Tissue organs displayed some changes in trace element concentrations manifested as a reduction in the concentration of Cu in both liver and kidney and noticeable increase in kidney (Zn and Ca). On histopathological examination, a dilatation of the central vein and central lobular, hepatocellular vacuolar degeneration and necrosis were observed. The necrotic cells, either appeared with pyknotic nuclei or without any nuclear structure.
2- Injection of iron dextran caused an increase in AST, ALP, bilirubin, iron status (serum iron, TIBC and transferrin), creatinine, TG, WBCs and liver MTs as well as liver and kidney LPO and ROS. Noticeable decrease in liver and kidney GSH content, liver superoxide dismutase (SOD) activity, serum albumin and A/G ratio were also recorded. Some changes in trace element concentrations were manifested as an increase in liver and kidney Fe while the concentration of Mg decreased in kidney and Cu in the liver. Histopathological examinations showed dilatation of the hepatic sinusoids and hepatocellular degenerative and necrotic changes with marked appearance of dark pigment engulfed by Kupffer cells.
3- Exposure to the toxicity of both iron dextran and γ-irradiation revealed similar disturbances in the majority of parameters as in γ-irradiation or iron dextran, except for trace elements which recorded an increase in liver Cu,
Mn, Ca, and Fe and a decrease in Mg, while an increase in kidney (Mg and Ca) and reduction in Cu were also observed. As for histological examination, cumulative damage in both iron dextran and radiation was observed.
4- Treatment of rats with naringin and ID alone or in combination with γ- irradiation has shown an ameliorative effect on (AST, ALT, ALP), total bilirubin, glucose, serum iron, TIBC, transferrin and ferritin, urea and creatinine levels, lipid profile (CH, TG, LDL-c, HDL-c) abnormalities and hematological parameters (WBCs, RBCs, Hb) and serum total protein, albumin and A/G ratio were also recorded. Concerning the oxidative parameters naringin decreased the lipid peroxidation and ROS production and increased the concentrations of GSH and MTS and the activity of SOD in both liver and kidney tissues. A retention of Zn, Cu, Mn, CA, Fe was observed in liver and kidney tissues. Naringin had also, a partial ameliorative effect to the histological damage produced.
According to the preceding findings, it could be concluded that:
• Administration of NIN can be effective in modulating the severity of liver and kidney function tests, trace element contents and oxidative damage induced by γ-radiation as well as ID toxicity in liver and kidney tissues.
• The protective effect of naringin could be retained to its ability to scavenge free radical species by inhibiting some enzymes or chelating trace metals involved in free radical production, in addition to enhancing the antioxidant defense system, suppress lipidperoxidation and restoring some of the metalloelements in liver and kidney tissues.