Effects of Chlorpromazine on the Activities of Antioxidant Enzymes and Lipid Peroxidation in the Various Regions of Aging Rat Brain

Roy, Deodutta; Pathak, Deena N.; Singh, Rameshwar

doi:10.1111/j.1471-4159.1984.tb02728.x

Cited by 58 publications

(15 citation statements)

References 24 publications

(24 reference statements)

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“…Since GST is likely to be involved in a variety of functions ranging from detoxification of lipid peroxidation products and xenobiotics to intracellular transport of hormones [3,4], its elevation by drugs in the ageing brain will be of considerable interest. Chlorpromazine stimulates antioxidant enzymes such as glutathione peroxidase and superoxide dismutase [16], and also has anti-lipid peroxidant and anti-lipofuscin effects [15,16]. The present data thus show an additional effect of this drug on another enzyme related to antioxidative stress.…”

Section: Discussionsupporting

confidence: 49%

“…The drug was injected intraperitoneally at a dose of 10 mg/kg body weight on alternate days. This dose was based on our earlier studies from this laboratory [16]. Control rats received the same volume of physiological saline solution.…”

Section: Chlorpromazine Effectmentioning

confidence: 99%

“…Chlorpromazine is widely used in therapeutics for the treatment of psychiatric (psychotic) disorders. The drug also inhibits the formation of lipofuscin [15,16] and lipid peroxidation, and activates antioxidant enzymes, such as glutathione peroxidase, glutathione reductase, etc. [16].…”

Section: Introductionmentioning

confidence: 99%

“…The drug also inhibits the formation of lipofuscin [15,16] and lipid peroxidation, and activates antioxidant enzymes, such as glutathione peroxidase, glutathione reductase, etc. [16]. It will, therefore, be of interest to find out whether this drug has any influence on the brain GST activity.…”

Section: Introductionmentioning

confidence: 99%

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Glutathione-S-Transferase in the Ageing Rat Brain Cerebrum and the Effect of Chlorpromazine

Gopal

Sriram²,

Sharma³

et al. 1999

Gerontology

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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 folllowed 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.

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Section: Discussionsupporting

confidence: 49%

Section: Chlorpromazine Effectmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Glutathione-S-Transferase in the Ageing Rat Brain Cerebrum and the Effect of Chlorpromazine

Gopal

Sriram²,

Sharma³

et al. 1999

Gerontology

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“…A number of investigations have been made into the cellular and regional differ ences in the accumulation of lipopigments in the central nervous system of man [Obersteiner, 1903;Friede, 1962;Braak, 1974;Braak, 1978;Mann et al, 1978;Dowson, 1982] and other vertebrates [Dayan, 1971;Ferrendelli et al, 1971;Samorajski et al, 1968;Brizzee et al, 1974;Nandy and Vijayan, 1979], The differential pattern of lipo pigment accumulation in discrete neuron populations has been assumed to reflect re gional differences in energy metabolism and lipid peroxidation [Friede, 1962;Fer rendelli et al, 1971;Sohal, 1981;Roy et al, 1984],…”

mentioning

confidence: 99%

Difference in the Age-Related Accumulation of Lipopigments in the Adrenergic and Nonadrenergic Peripheral Neurons in the Male Rat

Koistinaho¹

1986

Gerontology

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The age-related accumulation of lipopigments was determined in the adrenergic and nonadrenergic peripheral neurons of the rat using a microspectrofluorometric method and electron microscopy, 3-, 12- and 30-month-old rats were used. The rate of lipopigment accumulation was greater in nonadrenergic than adrenergic neurons. The nonadrenergic neurons showed an emission maximum at 500 nm, while the emission maximum of adrenergic neurons was at 515–520 nm. Electron microscopy revealed a neuromelanin-like component in the pigment bodies of adrenergic neurons but not in nonadrenergic neurons. The results indicate that age-related lipopigment accumulation has a differential and selective pattern also in the peripheral nervous system.

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Iron‐dependent peroxidation of rat brain: A regional study

Subbarao

Richardson

1990

J of Neuroscience Research

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Iron has been shown to initiate a variety of free radical reactions in biological systems. The present study examined the in vitro susceptibility of homogenates prepared from different regions of rat brain to iron-induced peroxidation. Among the regions studied, basal thiobarbituric acid-reactive product (TBAR) formation is highest in the cerebellum and amygdala, intermediate in the cortex, hippocampus, and neostratium, and lowest in the hypothalamus, midbrain, and brainstem. In the presence of 200 microM FeCl3, there is a 20-25-fold increase in the net TBAR formation in all regions, with TBAR formation in the cerebellum and amygdala being significantly higher than in the midbrain and brainstem. Time-course and dose-response studies of iron-induced peroxidation showed that the cerebellum and amygdala are the most susceptible regions with respect to concentration of iron and duration of the incubation time, whereas the midbrain and brainstem are the least affected areas. Following low-speed (1,000 g) centrifugation of brain part homogenates, TBAR formation in the supernatant fractions is quite uniform across regions, while the pellet fractions give the same regional variations as the whole homogenates. TBAR formation in both fractions is increased 20-30-fold in the presence of 200 microM iron. Brain tissue TBAR formation induced by 200 microM iron is inhibited by the iron chelator desferrioxamine (IC50 = 600 microM), by Tris buffer pH = 8.0 (2.5 mM Tris gives 50% inhibition by trapping hydroxyl radicals), and by high concentrations of the cyclooxygenase inhibitor indomethacin (IC50 = 1.2 mM).

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Effects of Chlorpromazine on the Activities of Antioxidant Enzymes and Lipid Peroxidation in the Various Regions of Aging Rat Brain

Cited by 58 publications

References 24 publications

Glutathione-S-Transferase in the Ageing Rat Brain Cerebrum and the Effect of Chlorpromazine

Glutathione-S-Transferase in the Ageing Rat Brain Cerebrum and the Effect of Chlorpromazine

Difference in the Age-Related Accumulation of Lipopigments in the Adrenergic and Nonadrenergic Peripheral Neurons in the Male Rat

Iron‐dependent peroxidation of rat brain: A regional study

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