الفهرس 
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Abstract
6. SUMMARY
Melatonin is a hormone secreted by the pineal gland, which is a small gland with a diameter of 7.2 mm located in the brain. Melatonin is found in all cells of every living organism. Melatonin is responsible for regulating the circadian rhythm in both humans and animals. In humans, the process of secretion of melatonin occurs where the eyes face the darkness, which causes a feeling of drowsiness during the night and helps him sleep. Its effect is lost when the light is seen, and a person wakes up from sleep, just as the sun rises every day. In the field of pharmacy, this hormone is available in the form of powder or pills and is used to overcome insomnia.
It has a wide range of effects, including sleep regulation, anti-aging, anti-inflammatory, and anti-oxidation activities. Melatonin helps to regulate bone metabolism through promoted alkaline phosphatase (ALP) activity in blood and bone tissue. So the present study was conducted to :
1- Investigate the effect of using different light regimes on melatonin secretion and its effect on bone density in the adult male albino rats.
2- Improve the performance of the skeleton by subcutaneous injection of melatonin in the aged female rats.
3- Study the effect of using different light wave length on melatonin secretion in pregnant female albino rats and its effect on the bone density and the bone mineral content in the fetus.
Three main experiments were carried out:-
The First Experiment: Effect of different light regimes and melatonin injection (50µg/100gB.W) for 12 weeks in adult male albino rats.
The present study was designed to examine the effect of using different light regimes on melatonin secretion and bone physiology .Forty male albino rats (6 months old) were divided into four equal groups, vehicle-treated control group (exposed to 12 hours light : 12 hours dark),vehicle treated group exposed to 24 hours dark, vehicle treated group exposed to 24 hours light and MEL treated(subcutaneous injection of 50 μg/100 g b.w MEL) and exposed to 24 hours light. After 12 weeks of treatment, blood and bone samples were collected. Bones grossly examined and fixed using neutral formalin for histopathological examination and Measurement of RANKL mRNA levels by real time PCR . Also Serum total and bone specific alkaline phosphatase (TALP and BALP), corticosterone, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) activity .Moreover, blood and bone minerals contents were determined as calcium ( Ca), phosphorus (P),zinc (Zn), copper (Cu), iron ( Fe) and manganese (Mn) were determined. Some bone chemical parameters as insulin like growth factor (IGF ) and Procollagen Type I N-Terminal Propeptide (PINP) were determined. Moreover, calcitonin (CT) and parathyroid hormones (PTH) were determined. There were a significant increase in bone mass, BALP and SOD activities and GSH in Dark and MEL treated rats. Moreover, a significant increase in serum Ca level and serum and bone Zn and Fe and significant decrease in MDA and corticosterone level in 24 hours dark treated group were observed. There was a significant increase in IGF, PINP and CT , and down regulation to RANKL in dark exposed group.
In conclusion , exposure of adult male albino rat to the darkness stimulate melatonin secretion which have appositive effect on bone physiology and mineral balance.
The Second Experiment: Effect of melatonin on bone remodeling in (osteoporotic) aged female rats.
The aim of the 2nd experiment was to determine the effectiveness of melatonin administration in treatment of aged (osteoperotic) female albino rats.
Twenty female rats (24 months old) were divided into two equal groups, vehicle-treated control and MEL treated daily (subcutaneous injection of 100 μg/100 g b.w MEL). After 8 weeks of treatment, blood and bone samples were collected. Bones grossly examined and fixed using neutral formalin for Histopathological examination and Measurement of activated receptor activator of nuclear factor-κB ligand (RANKL mRNA) levels by real time PCR . Serum total and bone specific alkaline phosphatase (TALP and BALP), corticosterone, c-reactive protein(CRP) , malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) activity and serum and bone calcium ( Ca), zinc (Zn), copper (Cu), iron ( Fe) and manganese (Mn) were determined. Some bone chemical parameters as insulin like growth factor (IGF ) and Procollagen Type I N-Terminal Propeptide (PINP) were determined. Moreover, calcitonin (CT) and parathyroid hormones (PTH) were determined. There was a significant increase in bone mass, BALP and SOD activities and GSH in MEL treated rats. Moreover, a significant increase in serum Ca level and serum and bone Zn and Fe and significant decrease in serum MDA and corticosterone level in treated group. There was a significant increase in IGF,PINP and CT , a significant decrease and CRP in treated aged group and down regulation to RANKL in MEL treated group.
In conclusion , melatonin demonstrated a significant beneficial effects in preventing aging and in bone related diseases.
The Third Experiment: Effect of maternal exposure to different light wave length on melatonin secretion in dams and fetal bone growth.
The present study was designed to examine the effect of using different light wave length on melatonin secretion in dams and its effect on fetal growth. Thirty pregnant female albino rats age of (6 month) were allocated into three equal groups (10 rats /group) control group which exposed to 12 hrs dark / 12 hrs light cycle, group exposed to red color light for 12 hours at night and group exposed for 12 hours blue color light at night. At the day eighteen of pregnancy, females were euthanized with ether, blood collected , sacrificed and the feti were collected and counted to calculate the litter size. . Dam’s bones and feti grossly examined and fixed using neutral formalin for Histopathological examination. Serum total and bone specific alkaline phosphatase (TALP and BALP), corticosterone, melatonin (Mel) , malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) activity were determined . Serum and bone (in both dams and feti) calcium ( Ca), zinc (Zn), copper (Cu), iron ( Fe) and manganese (Mn) were determined. Some bone chemical parameters as insulin like growth factor (IGF ) and Procollagen Type I N-Terminal Propeptide (PINP) were determined. and parathyroid hormones (PTH) were determined. There was a significant increase in litter size in red treated group. There was a significant increase in bone mass, BALP and SOD activities and GSH in red treated pregnant rats. Moreover, a significant increase in serum Ca level and serum and bone Zn and Fe and a significant decrease in serum MDA and corticosterone level in red light exposed group. There was a significant increase in IGF, PINP, MEL and CT, in red light exposed pregnant female rats . In conclusion , exposure of pregnant female rats to red light decrease corticosterone (anti stress) and increase antioxidant enzymes which have appositive impact on the fetal development.
In conclusion, The results of the present study demonstrated a significant beneficial effects of using melatonin in preventing aging and in bone related diseases. Melatonin is an important regulator of the complex embryo-fetal developmental processes. First, it induces the circadian rhythmicity in the offspring. Second, it appears to have a direct developmental effect on nervous and endocrine system. It also protects the highly metabolic ROS producing organs in the development from the oxidative stress damage.
Also , it recommended to use dim red lights during night due to it is less likely to shift circadian rhythm and suppress melatonin as blue lights and avoid looking at bright screens before going to bed.