الفهرس 
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Abstract
Biochemical effects of rutin and curcumin treatment as natural antioxidants on iron overload induced hepatic oxidative stress in experimental rats. Eighty white male albino rats (8-10 week’s old) of average body weight 180-220 gm. Rats were kept at constant environmental and nutritional conditions throughout the periods of the experiment, and fresh, clean drinking water was supplied ad libitum. Antioxidants compounds and dosages: Rutin was dissolved in propylene glycol solvent and was administrated to animals in a daily oral dose of 50 mg/kg body weight (b.w.). Curcumin was dissolved in dimethyl sulfoxide (DMSO) solvent and was administrated to animals in a daily oral dose of 100.0 mg/kg body weight. Induction of iron overload: Ironoverloadwasinducedby intraperitoneal injectionsofsix doses (three doses per week) of ferric hydroxide polymaltose complex of 100 mg/kg b.w. The experimental design: Animal grouping: Rats were randomly divided into four equal groups: each group contain twenty rats as follows: Group I (control): received intraperitoneal injectionwithsaline only and served as control for all other groups. Group II (iron overload): received six doses (three doses per week) of 100 mg/kg b.w. of ferric hydroxide polymaltose complex administrated by IP-injection. Group III (rutin+iron overload): received six doses (three doses per week) of 100 mg/kg b.w. of ferric hydroxide polymaltose by IP-injection, followed by daily oral administration of rutin at a dose level of 50 mg/kg b.w. until the sacrificed day. Group IV (curcumin+iron overload): received six doses (three doses per week) of 100 mg/kg b.w. of ferric hydroxide polymaltose by IP-injection, followed by daily oral administration of curcumin (100 mg/kg b.w.). Sampling: Blood samples and liver tissue specimens were collected from all animals groups (control and experimental groups) three times along the duration of the experiment after three, four and five weeks from the onset of administration of iron and antioxidants. 1- Blood samples: Blood samples were collected by ocular vein puncture in dry, clean, and screw capped tubes. Sera were separated by centrifugation at 3000 r.p.m for 15 minutes. The clear sera were received in dry sterile sample tubes, then kept in a deep freeze at -20°C until be used for the subsequent biochemical analysis. 2- Liver tissue specimens: At the end of each experimental period, rats were sacrificed by cervical decapitation. The liver specimens were quickly removed and weighted, then per fused with cold saline to exclude the blood cells and then blotted on filter paper, and stored at -20°C. Briefly, half of liver tissues were cut, weighed and minced into small pieces, homogenized with a glass homogenizer in 9 volume of ice-cold 0.05 mM potassium phosphate buffer (pH7.4) to make 10% homogenates. The homogenates were centrifuged at 5,000 r.p.m for 15 minutes at 4°C, then the supernatants were stored in deep freeze at -8oC until be used for the subsequent biochemical analysis. Biochemical analysis: 1-In serum: All sera were used for the determination of the following parameters: serum iron profile (iron, total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC), transferrin (Tf), transferrin saturation % (TS %) and ferritin), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein and albumin. 2- In liver tissue homogenate: All the liver tissue homogenates were used for the determination of the following biochemical parameters: iron, malondialdehyde (MDA), reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), nitric oxide (NO) and total nucleic acid (TNO). The obtained results were summarized in the fallowing: 1- Serum iron: 1. Iron overload in rats induced a significant increase in serum iron concentration allover the periods of the experiment when compared with the control group. 2. Rutin and curcumin treatment in iron overloaded rats resulted in a significant decrease in serum iron concentration allover the experimental periods when compared with the IOL non treated rats. 2- Serum total iron binding capacity (TIBC): 1. Iron overload in rats caused a significant increase in serum TIBC concentration allover the experimental periods when compared with the control group. 2. Rutin and curcumin treatment in iron-loaded rats resulted in a significant decrease in serum TIBC concentration allover the periods of the experiment when compared with the IOL non treated rats. 3- Serum unsaturated iron binding capacity (UIBC): 1. Iron overload in rats induced a significant decrease in serum UIBC concentration after three and four weeks when compared with the control group. 2. Rutin treatment in iron overloaded rats caused a significant increase in serum UIBC concentration allover the periods of the experiment when compared with the IOL non treated rats. 3. Curcumin treatment in iron overloaded rats induced a significant increase in serum UIBC conc. after four and five weeks when compared with the IOL non treated group. 4- Serum transferrin (Tf): 1. Iron overload in rats induced a significant increase in serum Tf concentration after three and five weeks when compared with the control group. 2. Rutin and curcumin treatment in IOL rats caused a significant decrease in serum Tf conc. after three and five weeks when compared with the IOL non treated rats. 5- Serum transferrin saturation percent (TS%): 1. Iron overload in rats resulted in a significant increase in TS% allover the periods of the experiment, when compared with the control group. 2. Rutin treatment in iron overloaded rats caused a significant decrease in TS% allover the experimental periods when compared with the IOL non treated rats. 3. Curcumin treatment in iron overloaded rats induced a significant decrease in TS% after four and five weeks when compared with the IOL non treated group. 6- Serum Ferritin: 1. Iron overload in rats induced a significant increase in serum ferritin allover the periods of the experiment when compared with the control group. 2. Rutin and curcumin treatment in IOL rats caused a significant decrease in serum ferritin after five weeks only when compared with the IOL non treated rats. 7. Serum aspartate aminotransferase (AST): 1. Iron overload in rats induced a significant increase in serum AST activity allover the periods of the experiment when compared with the control group. 2. Rutin and curcumin treatment in iron overloaded rats caused a significant decrease in serum AST activity allover the experimental periods when compared with the iron overload non treated rats. 8. Serum alanine-aminotransferase (ALT): 1. Iron overload in rats induced a significant increase in serum ALT activity allover the experimental periods, when compared with the control group. 2. Rutin and curcumin treatment in IOL rats caused a significant decrease in ALT activity allover the experimental periods, when compared with the IOL non treated rats. 9- Serum total protein: 1. Iron overload in rats resulted in a significant decrease in serum total protein conc. after three and five weeks when compared with the control group. 2. Rutin and curcumin treatment in iron overloaded rats induced a significant increase in serum total protein conc. allover the periods of the experiment when compared with the IOL non treated rats. 10- Serum albumin: 1. Iron overload in rats resulted in a significant decrease in serum albumin conc. allover the periods of the experiment when compared with the control group. 2. Rrutin and curcumin treatment in iron overloaded rats caused a significant increase in serum albumin conc. allover the experimental periods when compared with the IOL non treated rats. 11-Liver iron: 1. Iron overload in rats resulted in a significant increase in liver iron concentration allover the periods of the experiment when compared with the control group. 2. Rutin treatment in IOL rats induced a significant decrease after four weeks in liver iron conc. after three weeks only when compared with the IOL non treated rats. 3. Curcumin treatment in iron overloaded rats caused a significant decrease in liver iron conc. allover the experimental periods when compared with the IOL non treated group. 12. Liver L-malondialdehyde (L-MDA): 1. Iron overload in rats induced a significant increase in liver L-MDA concentration allover the periods of the experiment when compared with the control group. 2. Rutin treatment in IOL rats caused a significant decrease in liver L-MDA conc. allover the experimental periods when compared with the IOL non treated rats. 3. Curcumin treatment in iron overloaded rats resulted in a significant decrease in liver L-MDA conc. after four weeks only when compared with the IOL non treated group. 13. Liver reduced glutathione (GSH): 1. Iron overload in rats resulted in a significant decrease in liver GSH level allover the periods of the experiment when compared with the control group. 2. Rutin and curcumin treatment in iron overloaded rats caused a significant increase in liver GSH level after five weeks only when compared with the IOL non treated rats. 14. Liver glutathione peroxidase (GPx): 1. Iron overload in rats induced a significant increase in liver GPX activity after three weeks followed by a significant decrease after four weeks when compared with the control group. 2. Rutin treatment in IOL rats resulted in a non significant decrease in liver GPX activity after three and five weeks followed by a non significant increase after four weeks when compared with the IOL non treated rats. 3. Curcumin treatment in iron overloaded rats caused a non significant decrease in liver GPX activity after three and four weeks followed by a non significant increase after five weeks when compared with the IOL non treated group. 15. Liver catalase (CAT): 1. Iron overload in rats resulted in a significant decrease in liver CAT activity allover the experimental periods, when compared with the control group. 2. Rutin and curcumin treatment in iron overloaded rats caused a significant increase in liver CAT activity allover the experimental periods when compared with the IOL non treated rats. 16. Liver superoxide dismutase (SOD): 1. Iron overload in rats induced a significant decrease in liver SOD activity allover the periods of the experiment when compared with the control group. 2. Rutin and curcumin treatment in iron overloaded rats caused a significant increase in liver SOD activity allover the experimental periods, when compared with the IOL non treated rats. 17. Liver nitric oxide (NO): . Iron overload in rats induced a significant increase in liver NO concentration allover the periods of the experiment, when compared with the control group. 2. Rutin and curcumin treatment in iron overloaded rats resulted in a significant decrease in liver NO concentration allover the experimental periods when compared with the IOL non treated rats. 18. Liver Total nucleic acid (TNA): 1. Iron overload in rats resulted in a significant decrease in liver TNA concentration after four weeks only when compared with the control group. 2. Rutin and curcumin treatment in iron overloaded rats caused a non significant increase in liver TNA conc. allover the experimental periods when compared with the IOL non treated rats.