الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 239 |  |  |
| | | from | 239 | | |
Abstract
The steadily increasing applications of radiation in clinical practice, industrial and agricultural activities, on top of residual radio-activity resulting from nuclear test explosions, have a measurable impact contributing to possible radiation hazards in humans. Control of radiation hazards is considered as one of the most important challenges in order to protect our lives from radiation damage. Radiation injury to living cells is, to a large extent, due to oxidative stress. Free radicals react with cellular macromolecules and cause cell dysfunction and mortality. Carnosine, (β-alanyl-L-histidine), a naturally occurring dipeptide, possesses various pharmacological properties. It is reported as a good scavenger against free radical generation, a powerful consumer of superoxide, singlet oxygen and hydroxyl radicals, thereby contributing significantly to the intracellular antioxidant defense system.
The objective of the present study is to elucidate the role of oxidative stress, neurotransmitters alteration and mitochondrial damage in the severity of biochemical disorders in brain tissues of γ-irradiated rats. In addition, the role of carnosine in modulating the severity of radiation-induced biochemical changes was investigated
Male albino rats Rattus rattus (100 ± 10 g), average 3 months old were used as experimental animals. Carnosine was dissolved in distilled water and administered via gavages, to rats at doses of 50 mg/Kg body weight/day. Carnosine was prepared freshly just before its administration daily.
Experimental animals were divided into five groups as follows:
1- Control group: Rats received distilled water via gavages during 24 successive days (n=18).
2- Carnosine-treated group: Rats received Carnosine (50 mg/Kg/day) via gavages during 28 successive days (n=18).
3- γ-irradiated group: Rats received distilled water via gavages during 14 successive days before whole body gamma irradiation with 5Gy and continued during 14 successive days after irradiation with distilled water (n=18).
4- Carnosine-treated pre γ-irradiated group: Rats received Carnosine (50 mg/Kg/day) during 14 successive days before whole body gamma irradiation with 5Gy and continued with distilled water (n=18).
5- Carnosine-treated pre and post γ-irradiated group: Rats received Carnosine (50 mg/Kg/day) during 14 successive days before whole body gamma irradiation with 5Gy and during 14 successive days after irradiation (n=18).
Animals were sacrificed 1st, 7th and 14th days post γ-irradiation. Blood was collected by heart puncture and centrifuged at 3000 r.p.m. for 15 minutes to separate the serum. The two cerebral hemispheres were rapidly excised for the further biochemical analysis.
The results obtained could be summarized as follows:
1- Oxidative stress in brain tissues:
Whole body gamma irradiation of rats with 5 Gy provoked oxidative stress in brain and kidney tissues. A significant increase in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glucose-6-phosphate dehydrogenase (G-6-PDH) activities and glutathione (GSH) content were recorded on the 1st day post γ-irradiation, followed by a significant decrease on the 7th and 14th day post γ-irradiation. Alteration in antioxidant biomarkers was concomitant with a significant increase in the content of oxidant biomarkers: thiobarbituric reactive substances (TBARS), protein carbonyls (CO) and advanced oxidation protein products (AOPPs), on the 1st, 7th and 14th day post γ-irradiation, compared to control values.
2- Mitochondrial damage in brain tissues:
Whole body exposure of rats to 5 Gy induced significant increases in the levels of mitochondrial calcium (Ca+2) and significant decreases in the activity of creatine phosphokinase (CPK) and glutamate dehydrogenase (GDH) enzymes in the mitochondria of brain and kidney tissues on the 1st, 7th and 14th day post γ-irradiation, compared to control values.
3- Neurotransmitters alterations in brain tissues:
Whole body exposure of rats to 5 Gy induced a significant decrease in the level of brain catecholamines (dopamine (Dopa), nor epinephrine (NE) and epinephrine (EPI)), that starts in the 1st day up to the 14th day post γ-irradiation. A significant increase of monoamine-oxidase (MAO) activity was recorded the 7th and 14th day post γ-irradiation. A significant increase in brain serotonergic activity (5-HIAA/5-HT) was recorded at the 7th and 14th day post γ-irradiation.
4- Modulator effect of carnosine:
Supplementation of rats with Carnosine, via gavages, at a dose of 50 mg/day/kg body weight, for 28 successive days (14 day before and 14 days after γ-irradiation) has modulated radiation-induced oxidative stress, mitochondrial damage and neurotransmitter alterations in brain tissues evidenced by a significant increase of SOD, CAT, GSH-Px, G-6-PDH activities and GSH content, associated to a significant decrease of TBARS, CO and AOPP, compared to their corresponding values in γ- irradiated rats. Significant amelioration of CPK, and GDH activities and Ca +2 levels were recorded in brain mitochondria. In addition, significant amelioration in the level of 5-HT, Dopa, NE and EPI levels, MAO activity and 5-HIAA/5-HT was recorded in brain tissues.