دانلود رایگان مقاله انگلیسی تاثیر سالخوردگی بر مسیر مصنوعی ملاتونین پلاسما - الزویر 2018

ABSTRACT

Ageing affects various physiological and metabolic processes in a body and a progressive accumulation of oxidative damage stands out as often used explanation. One of the most powerful scavenger of reactive oxygen species (ROS) in all organs is melatonin. A majority of melatonin supplied to the body via blood originates from the pineal gland. However, we have been interested in a locally produced melatonin. We have used 2.5- and 36-months-old Wistar rats. Tissues were collected and gene expression of AA-NAT and ASMT, the two key enzymes in a synthesis of melatonin, was determined in brain, liver, kidney, heart, skin, and intestine. Since melatonin can influence antioxidant enzymes, the activity of superoxide dismutase (SOD) and catalase (CAT), and the level of GSH were measured in liver. In addition, Copper (Cu), Zinc (Zn), and Manganese (Mn) were also determined in liver since these microelements might affect the activity of antioxidant enzymes. The expression of AA-NAT and ASMT was increased in liver and skin of old animals. A positive correlation in AA-NAT and ASMT expression was observed in liver, intestine and kidney. Moreover, the activity of CAT enzyme in liver was increased while SOD activity was decreased. SOD and CAT were probably affected by the observed decreased amount of Cu, Zn, and Mn in liver of old animals. In our model, extrapineal melatonin pathway in ageing consisted of complex interplay of locally produced melatonin, activities of SOD and CAT, and adequate presence of Cu, Zn and Mn microelements in order to defend organs against oxidative damage.

4. Discussion

This study was performed in order to provide a better understanding of melatonin synthetic pathway in relation to the ageing processes. Based on the obtained results, significant differences existed in the expression of the AA-NAT and ASMT genes, in the activity of SOD, CAT and GSH-Px, and the level of Mn, Zn and Cu between young and old individuals. We have used 3-years-old and 2.5-months-old rats in our experiments. To the best of our knowledge, this is the first time that melatonin synthetic pathway was analyzed in such old rats. Although the role of the serum melatonin in many age-related diseases of advanced age is well known, the role of locally present melatonin in ageing tissue is not clearly determined. The expression of AA-NAT and ASMT, the key enzymes of melatonin synthesis, has been previously evaluated in various tissues (Stefulj et al., 2001; Uz et al., 2002; Slominski et al., 2002; Hong and Pang, 1995; Konturek et al., 2007) and it is mainly influenced by the exposure to different oxidative stress factors (Jaworek et al., 2003). Here, we investigated age-related melatonin production in peripheral tissues by measuring AA-NAT and ASMT gene expression