MAO inhibitors and oxidant stress in aging brain tissue

Abstract

The process of aging presents itself with various alterations in physiological events. Among many theories, the free radical (FR) theory of aging which reflects the FR damage to cellular components is accepted as one of the most important theories. Recently, the increases in catecholamine metabolism in aging have also attracted attention, and monoamine oxidase (MAO), a key enzyme in this process has been extensively studied. The aim of this study was to assess the role of FR species via MAO, a possible source of FRs, in physiological aging by determining the lipid peroxidation products (LPP) (malondialdehyde, diene conjugates) and antioxidant enzyme levels (superoxide dismutase (SOD) and catalase (CAT) in young (3 months old, n=10) and aging (16–18 months old, n=10) rat brain tissues of Swiss male albino rats. In the second part of the study, the same parameters were determined after the acute administration of MAO inhibitors (deprenyl and pargyline, 25 mg/kg i.p.) to investigate whether these agents have any beneficial effects in reducing oxidant stress via inhibition of MAO. In old rat brains, MAO activities showed a significant increase ( P=0.000) in addition to an insignificant increase in LPP, while SOD ( P=0.007) and CAT activities showed a decrease with advancing age. After the acute administration of both deprenyl and pargyline, a significant decrease in the MAO activities of both young ( P=0.0002 for each) and aging rats ( P=0.0002 for deprenyl and P=0.0001 for pargyline) were observed. It was noted that deprenyl causes a significant increase in CAT activity ( P<0.05) but a significant decrease in SOD activity ( P<0.05) in young rats, while it causes only a significant increase in SOD activity in aging rats ( P<0.05). Both deprenyl and pargyline cause a significant decrease in conjugated diene levels of aging rats ( P<0.05). These results confirm the role of catecholamine oxidation and MAO activity as one of the causative factors in increased oxidant stress during aging. By reducing the oxidant stress observed in aging brain, MAO inhibitors, especially deprenyl, may contribute to the control of the aging process.