Glutathione-S-transferase in the ageing rat brain cerebrum and the effect of chlorpromazine.

Lipid peroxidation increases during ageing and has been implicated in the pathogenesis of degenerative processes associated with ageing. Despite the importance of the enzyme glutathione-S-transferase (GST) in the biotransformation and detoxification of lipid peroxidation products, there have been extremely limited studies of GST in the ageing brain. The drug chlorpromazine is known to have an activating influence on the activities of certain antioxidant enzymes (glutathione peroxidase, superoxide dismutase, etc.) and it also has anti-lipid peroxidative and anti-lipofuscin influences. Therefore, information about the age-related changes in brain GST and the effect of chlorpromazine on it in the ageing brain will be of further interest. We have, therefore, studied the effect of age on the activity of GST in the whole homogenate and cytosol fractions from the cerebral hemispheres of rats aged 1, 2, 3, 6, 12, 18 and 24 months. The effect of chlorpromazine treatment (10 mg/kg i.p. on alternate days for 6 months) was examined in the whole homogenate and cytosol fraction from the cerebral hemispheres of 6-, 12-, 18- and 24-month-old rats. The results showed that the values for GST specific activities in the cytosol fraction from all the age groups were higher then those in the whole homogenate; and the pattern of age changes in the whole homogenate differed from that in the cytosol. In the cytosol fraction the enzyme activity showed several phases of alterations: a progressive increase at 3 months of age, followed by a steady level up to 12 months of age; this phase was followed by a fall in the activity (at 18 months of age) then turned to a gradual increase. In the whole homogenate there were two phases of alterations: a progressive increase up to 12 months of age, which then turned to a somewhat gradual decrease with ageing. Thus, the decline in GST activity during ageing was evident in both the whole homogenate and cytosol. The results from chlorpromazine experiments showed that the drug elevated the GST activity in 12-, 18-, and 24-month-old animals but not in the 6-month-old animals. The drug's effects were most profound in 12-month-old animals. In conclusion, this study demonstrated an impairment of brain GST activity during ageing and the results further showed that the drug chlorpromazine attenuated the age-related impairment in the enzyme activity. The enhancement of the GST status of the ageing brain following chlorpromazine treatment is indicative of an additional antioxidative property of this drug.