الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 4 |  |  |
| | | from | 4 | | |
Abstract
Aging is a physiological (nonpathogenic) process that occurs mainly as a slow, gradual and passive process. It has been reported to be conditioned by genetic factors in a proportion of 25-30%, while the remaining 70-75% is ruled by environmental factors, making it a possible target for therapeutic tools.
Aging involves a progressive decline of the body functions as a consequence of gradual cellular impairment due to a failure of the repair mechanisms.
Excess calories and lack of physical activity, in addition to the lack of antioxidants in diets, are among the causes of premature aging in different societies.
There are many researches on experimental animals showing that there is a relationship between reducing calories in food and taking metformin antioxidants such as vitamin C in specific proportions and increasing the average lifespan of these animals.
In this study, aging was induced in male albino rats by giving them doses of D-galactose (3 mg/kg) 5 times | Week for 6 weeks. Then the effect of three separate strategies was tested: including a) reducing calories (by two-thirds), or taking appropriate doses of b) vitamin C or c) metformin, or d) the combination of the three strategies in slowing the aging process in experimental male albino rats by monitoring D-gal enhanced aging and induced biochemical and histopathological alterations and the data were statistically analyzed to reach conclusions consequential.
For this purpose, sixty adult male rats, ranged between 200-250 grams in weight, were used in this study. They provided basal diet consisting of 70% carbohydrates, 3% fat, 21% protein, and divided them into two main groups
1- The control (n=10) without any treatment and served as normal control group.
2- The second main group contains 50 adult rats that injected (50% D-gal at dose of 3 mg per kg) subcutaneously 5 times a week for six weeks to induce the aging process (aging rats), which were divided into five subgroups as follows:
• Aged rats (n=10) received basal diet ad libitum without any other treatment for one month.
• Aged rats (n=10) received restricted diet with 30% off for one month without any other treatment.
• Aged rats (n=10) administered only vitamin C at a dose of 16mg/kg by oral gavage without any other treatments.
• Aged rats (n=10) administered metformin (35 mg per kg) by oral gavage for one month without any other treatment.
• Aged rats (n=10) received combined strategy of RC, vitamin C and metformin.
At the end of the entire experimental time, the animals were sacrificed and both livers and brains were removed. Portion of the liver was prepared for pathological study and the other portion kept frozen at -20oc for biochemical analysis, to achieve the aim of this study:
• To investigate D-galactose-induced biochemical alterations in liver and blood plasma. As well as the histopathological changes in brain and liver were investigated.
• The capability of these strategies either solely or in combination to reflect these changes.
In the biochemical analysis the following parameters were evaluated
In hepatic tissue:
• BCL2, P53 and BAX, were determined using PCR
• Foxo-3, JNK, AKT, and Nrf-2 were estimated using Western immunoplotting analysis
• Nf-kB in liver homogenate and cystatine-C in blood plasma were examined by ELISA technique.
• MDA, GSH and CAT were measured by Spectrophotometrical method.
• Estimation of neuro transmitters including Serotonin, Epinephrine and Nor-epinephrine was done by Spectrophlorometric method.
Conclusion:
Depending on the finding s of the present study, we could conclude that D-gal induced sever histopathological and biochemical deteriorations in the brain and liver of treated rats.
Histopathologically, D-gal dosed rats showed pathological symptoms. In brain, severe cortical congestion and diffuse gliosis with activated microglia cells were observed. In addition, multifocal areas of hemorrhages were detected in the meninges as well as, excessive hemorrhage was appeared in the brain stem.
Moreover, in liver showed multifocal areas of lytic necrosis which appeared as mononuclear inflammatory cells infiltration associated with eosinophilic karyorrhectic debris, Multifocally, portal areas and hepatocytes were infiltrated with inflammatory cells. Some examined sections showed macro and microvesicular steatosis of the periportal hepatocytes with increased number of bi-nucleated cells. Meanwhile, some individuals showed severely congested hepatic sinusoids.
Biochemical analysis demonstrated that D galactose administration impaired liver and brain. However D-gal caused upregulation of P53, BAX, JNK gene expression and elevation of MDA concentration. Also, the level protein expression of Cystatin-C, NFKP and nor epinephrine concentration were increased. Controversy, the levels of GSH and CAT were diminished. Likewise, the levels of Nrf2, FOXO-3 and AKT were depleted.
Contrariwise, administration of metformin, vitamin C and dropping calories intake ameliorated brain and liver injury and accelerated morphological, histological and functional repair of such organs, thus retarding the toxic effects of D galactose both at the functional and histological levels. So, decreasing calories and adding antioxidants beside metformin administration could be a hopeful way to control aging.
Collectively together, reducing diet calories, vitamin C and metformin sole treatments and also in combination reverted the biochemical and histological changes induced by D-gal as indicated by increment of GSH and CAT as well as Nrf2, FOX and AKT. Meanwhile.