ABSTRACT
A convincing link between oxidative stress and neurodegenerative diseases has been found with the knowledge that it actually damages neuronal cells in culture. We analyzed the effect of DL-alpha-lipoic acid on lipofuscin and Na(+)K(+) ATPase in discrete brain regions of young and aged rats. In aged rats, the level of lipofuscin was increased, and the activity of Na(+)K(+)ATPase was decreased. Intraperitoneal administration of lipoic acid to aged rats led to a duration-dependent reduction and elevation in lipofuscin and enzyme activity, respectively, in the cortex, cerebellum, striatum, hippocampus, and hypothalamus of the brain. These results suggest that lipoic acid, a natural metabolic antioxidant, should be useful as a therapeutic tool in preventing neuronal dysfunction in aged individuals.
Subject(s)
Brain/metabolism , Lipofuscin/metabolism , Sodium-Potassium-Exchanging ATPase/metabolism , Thioctic Acid/pharmacology , Aging , Animals , Antioxidants/pharmacology , Brain/pathology , Male , Neurons/metabolism , Rats , Rats, Wistar , Thioctic Acid/metabolismABSTRACT
The effect of DL-alpha-lipoic acid on lipid peroxidation and antioxidant enzymes were evaluated in various brain regions of young and aged rats. Lipoate contents of discrete brain regions were also measured. In aged rats, the activities of superoxide dismutase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase were low whereas thiobarbituric acid reactive substances were found to be high. Catalase activity in various brain regions was little altered in aged rats. Lipoic acid an antioxidant was administered intraperitoneally (100mg/kg body weight per day) for 7 and 14 days. Lipoate administered aged rats showed a duration dependent reduction in the level of lipid peroxidation and elevation in the activities of antioxidant enzymes. There was a rise in the level of lipoate in aged rats after supplementation of lipoate in all the brain regions examined. From our results we conclude that lipoate supplementation had a beneficial effect in both preventing and reversing abnormalities in ageing brain. This beneficial effect was associated with normalization of lipid peroxidation and partial restoration in the activities of various enzymatic antioxidants suggesting that lipoate supplementation could improve brain antioxidant functions in the elderly.
Subject(s)
Aging/metabolism , Antioxidants/pharmacology , Brain/drug effects , Lipid Peroxidation , Thioctic Acid/pharmacology , Animals , Antioxidants/administration & dosage , Brain/enzymology , Catalase/metabolism , Glucosephosphate Dehydrogenase/metabolism , Glutathione Peroxidase/metabolism , Glutathione Reductase/metabolism , Male , Rats , Rats, Wistar , Superoxide Dismutase/metabolism , Thioctic Acid/administration & dosageABSTRACT
Age-related impairments of cognitive and motor function have been linked to a number of deleterious morphological and functional changes involving different areas of the brain. Loss of neurotransmitters, their receptors and responsiveness to neurotransmitters are key manifestations of neurological ageing and age-related disorders. In the present investigation we have evaluated the effect of DL-alpha-lipoic acid on neurotransmitters in discrete brain regions of young and aged rats. The levels of neurotransmitters were found to be lowered in aged rats. Moreover, DL-alpha-lipoic acid treated aged rats showed a increase in the status of dopamine, serotonin and norepinephrine. The results of this study provide evidence that DL-alpha-lipoic acid (a potent antioxidant) treatment can improve neurotransmitters during ageing. Hence, it can be concluded that DL-alpha-lipoic acid act as a potent neuromodulator in the brain of aged rats.
Subject(s)
Aging/drug effects , Antioxidants/pharmacology , Brain/drug effects , Neurotransmitter Agents/metabolism , Thioctic Acid/pharmacology , Aging/metabolism , Animals , Brain/metabolism , Dopamine/metabolism , Male , Norepinephrine/metabolism , Rats , Rats, Wistar , Serotonin/metabolismABSTRACT
Ageing is characterized by a failure to maintain homeostasis under conditions of physiological stress, with an increasing susceptibility to disease and death. The accumulation of errors committed by faulty biochemical reactions over a vast period generates the cumulative effect observed during ageing. The most notable among the effects of ageing are the age-related disorders where free radicals are the major cause. When the level of free radicals increases because of diet, lifestyle, environment or other influences, it results in subsequent reduction of antioxidants. Reduced glutathione is one of the most fascinating molecules virtually present in all animal cells in often quite higher concentrations. An essential mechanism that accounts for most of the metabolic and cell regulatory properties of glutathione is the thiol disulfide exchange equilibria. We evaluated the age-associated alterations in glutathione dependent enzymes, glutathione and hydroxyl radicals in young and aged rats with respect to lipoate supplementation. In aged rats, activities of glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase and the level of glutathione were low, whereas the level of hydroxyl radical was higher than in the young ones. Administration of DL-alpha-lipoic acid, a thiol antioxidant intraperitoneally to the aged rats, led to a time-dependent reduction in hydroxyl radicals and elevation in the activities/level of glutathione systems. Hence it can be suggested that lipoate, a dithiol prevents the oxidation of reduced glutathione and protects its related enzymes from peroxidative damage.
Subject(s)
Aging/drug effects , Antioxidants/pharmacology , Glutathione Peroxidase/metabolism , Glutathione Reductase/metabolism , Glutathione Transferase/metabolism , Thioctic Acid/pharmacology , Aging/metabolism , Animals , Antioxidants/administration & dosage , Dietary Supplements , Glucosephosphate Dehydrogenase/metabolism , Glutathione/metabolism , Hydroxyl Radical/metabolism , Kidney/drug effects , Kidney/metabolism , Liver/drug effects , Liver/metabolism , Male , Rats , Rats, Wistar , Thioctic Acid/administration & dosageABSTRACT
Mitochondrial dysfunction appears to contribute to some of the loss of function accompanying ageing. Mitochondria from aged tissue use oxygen inefficiently impairing ATP synthesis and results in increased oxidant production. A high flux of oxidants not only damages mitochondria, but other important cell biomolecules as well. In the present investigation, the levels of lipid peroxidation, oxidized glutathione, non-enzymatic antioxidants and the activities of mitochondrial enzymes were measured in liver and kidney mitochondria of young and aged rats before and after lipoic acid supplementation. In both liver and kidney increase in the levels of mitochondrial lipid peroxidation and oxidized glutathione and decrease in the levels of antioxidants and the activities of mitochondrial enzymes were observed in aged rats. DL-alpha-lipoic acid supplemented aged rats showed a decrease in the levels of lipid peroxidation and oxidized glutathione and increase in the levels of reduced glutathione, vitamins C and E and the activities of mitochondrial enzymes like isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, NADH-dehydrogenase and cytochrome-c-oxidase. Thus, lipoic acid reverses the age-associated decline in endogenous low molecular weight antioxidants and mitochondrial enzymes and, therefore, may lower the increased risk of oxidative damage that occurs during ageing. From our results it can be concluded that lipoic acid supplementation enhances the activities of mitochondrial enzymes and antioxidant status and thereby protects mitochondria from ageing.
Subject(s)
Aging/metabolism , Antioxidants/pharmacology , Mitochondria, Liver/drug effects , Oxidoreductases/metabolism , Thioctic Acid/pharmacology , Animals , Antioxidants/administration & dosage , Ascorbic Acid/metabolism , Dose-Response Relationship, Drug , Glutathione/metabolism , Glutathione Disulfide/metabolism , Injections, Intraperitoneal , Kidney/drug effects , Kidney/metabolism , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/metabolism , Male , Mitochondria, Liver/enzymology , Rats , Rats, Wistar , Thioctic Acid/administration & dosage , Vitamin E/metabolismABSTRACT
The life span of a species is thought to be determined by the rate of mitochondrial damage which in turn is inflicted by free radicals in the mitochondria during the course of normal metabolism. The level of lipid peroxidation and antioxidants were measured in liver and kidney mitochondria of young and aged rats before and after DL-alpha-lipoic acid supplementation. In both liver and kidney, mitochondrial lipid peroxidation increased with age and a decrease in the enzymatic and non-enzymatic antioxidants were observed. DL-alpha-lipoic acid treated aged rats showed a decrease in the level of lipid peroxides and an increase in the antioxidant status. Our results conclude that supplementation of lipoic acid restores the depleted mitochondrial antioxidant status and suggest that it could be an effective therapeutic agent in treatment of age-associated disorders where free radicals are the major causative factor.
ABSTRACT
The effect of DL-alpha-lipoic acid on lipid peroxidation and antioxidants were evaluated in various brain regions of young and aged rats. In aged rats, the levels of ascorbic acid, alpha-tocopherol and glutathione were low whereas the lipid peroxidation rate, as revealed by malonaldehyde content, was found to be high. Lipoic acid, an antioxidant, was administered intraperitoneally (100 mg/kg body weight/day) for 7 and 14 days. Lipoate-administered aged rats brought about reduction in lipid peroxidation and elevation in the levels of antioxidants. The modulatory effect of lipoate in decreasing age-associated alterations observed in our study proves its role as a potent antioxidant in the brain of aged rats.
Subject(s)
Antioxidants/analysis , Brain/drug effects , Lipid Peroxidation/drug effects , Thioctic Acid/pharmacology , Animals , Ascorbic Acid/analysis , Brain/metabolism , Glutathione/metabolism , Male , Rats , Rats, Wistar , Vitamin E/analysisABSTRACT
We have attempted to evaluate the effect of DL-alpha-lipoic acid on nucleic acid and protein contents in young and aged rats. An age-associated decrease in the deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and protein contents were observed in aged rats. DL-alpha-lipoic acid was administered intraperitoneally (100 mg/kg body weight/day) to young and aged rats from 7 and 14 days. Lipoate administration demonstrated a substantial increase in nucleic acid and protein contents in aged rats. Hence it can be justified that lipoate is functionally efficient in helping the cell to recover from oxidative damage.
Subject(s)
Aging/metabolism , DNA/analysis , RNA/analysis , Thioctic Acid/pharmacology , Animals , Kidney/chemistry , Liver/chemistry , Male , Proteins/analysis , Rats , Rats, Wistar , Spleen/chemistryABSTRACT
Oxidative metabolism produces free radicals that must be removed from the cellular environment for the cell to survive. The levels of nonenzymic antioxidants involved in the elimination of free radicals were investigated in an attempt to correlate any changes in the levels of enzymic antioxidants during aging with changes in free radical mediated cellular damage. Antioxidants were measured in liver and kidney of young and aged rats with respect to DL-alpha-lipoic acid supplemented rats. In both organs lipid peroxidation damage (a marker of free radical mediated damage) increased with age, and a significant decrease in antioxidant systems was observed. Moreover, DL-alpha-lipoic acid treated aged rats showed a decrease in the level of lipid peroxides and an increase in the antioxidant status. The results of this study provide evidence that DL-alpha-lipoic acid treatment can improve antioxidants during aging and minimize the age-associated disorders in which free radicals are the major cause.
ABSTRACT
The effect of dl-alpha-lipoic acid on lipid peroxidation and antioxidants status has been studied in the blood of young and aged rats. dl-alpha-lipoic acid, an antioxidant, was administered intraperitoneally for 7 and 14 days. Enzymatic and non-enzymatic antioxidant levels decreased with age but this decrease was attenuated by dl-alpha-lipoic acid. Lipid peroxide levels increased with age, and were decreased by lipoic acid administration. These results suggest that biochemical lesions which are considered to be part of the normal ageing process are neutralized by dl-alpha-lipoic acid.