Carnitine and lipoate ameliorates lipofuscin accumulation and monoamine oxidase activity in aged rat heart.

In this study we have focused on the levels of lipofuscin, monoamine oxidase and cholesterol phospholipid ratio in the heart muscle of young, middle aged and aged rats. In parallel, we have also investigated the levels of carnitine and lipoic acid during aging. We observed an increase in lipofuscin accumulation and monoamine oxidase activity in both middle aged and aged rats. Levels of both carnitine and lipoic acid decreased along with a decrease in cholesterol phospholipid ratio. These changes were normalized upon cosupplementation of carnitine and lipoic acid. Our results thus reveal that carnitine along with lipoic acid can be used as an effective supplement against free radical induced damage to the cardiac tissue.

Modulatory role of grape seed extract on age-related oxidative DNA damage in central nervous system of rats.

Aging is the accumulation of diverse deleterious changes in the cells and tissues leading to increased risk of diseases. Oxidative stress is considered as a major risk factor and contributes to age related increase in DNA oxidation and DNA protein cross-links in central nervous system during aging. In the present study, we have evaluated the salubrious role of grape seed extract on accumulation of oxidative DNA damage products such as 8-OHdG and DNA protein cross-links in aged rats. Male albino rats of Wistar strain were divided into four groups: Group I, young control rats; Group II, young rats treated with grape seed extract (100 mg/kg b.wt.) for 30 days; Group III, aged control rats; Group IV, aged rats supplemented with grape seed extract (100 mg/kg b.wt.) for 30 days. Our results, thus, revealed that grape seed extract has inhibiting effect on the accumulation of age-related oxidative DNA damages in spinal cord and in various brain regions such as cerebral cortex, striatum and hippocampus.

Age associated changes in erythrocyte membrane surface charge: Modulatory role of grape seed proanthocyanidins.

Aging, a multifactorial process of enormous complexity is characterized by impairment of physio-chemical and biological aspects of cellular functions. It is closely associated with increased free radical production, which situation ultimately leads to devastation of normal cell function and membrane integrity. The present study was aimed to determine the effect of proanthocyanidins rich grape seed extract (GSP) on membrane surface charge density in erythrocytes during animal age associated oxidative stress. GSP (100 mg/day/kg body weight) was administered orally for 15 and 30 days to young and aged rats. Significant decrease in surface charge levels with concomitant increase in protein carbonyls and decrease in glycoprotein, antioxidants status was noted in erythrocytes of aged rats when compared with young rat erythrocytes. Duration dependent supplementation of GSP increased the erythrocyte surface charge density to near normalcy in aged rats. Decrease in protein carbonyls level and increase in glycoproteins as well as antioxidant status was observed in aged rat erythrocytes on GSP treatment. Thus, from our results, we conclude that GSP is an effective anti-aging drug in preventing the oxidative stress associated loss of membrane surface charge, which thereby maintains the erythrocyte membrane integrity and functions in elderly.

Age-related oxidative protein damages in central nervous system of rats: modulatory role of grape seed extract.

Oxidative stress has been shown to play a major role in aging and in neurodegenerative disorders. Protein modification is one of the important consequences of oxidative stress. In the present study, we evaluated the role of grape seed extract on memory, reactive oxygen species production, protein carbonyls (PCO), and thiol status in discrete regions of central nervous system of young and aged rats. Male albino rats of Wistar strain were divided into four groups: Group I--control young rats, Group II--young rats treated with grape seed extract (100 mg/kg BW) for 30 days, Group III--aged control rats and Group IV-aged rats supplemented with grape seed extract (100 mg/kg BW) for 30 days. Memory loss was observed in the aged rats. Age associated increase in reactive oxygen species production and protein oxidation was observed in the spinal cord; cerebral cortex, striatum and the hippocampus regions of aged rats (Group III). The levels of total thiol, non-protein thiol, protein thiols were found to be significantly decreased in spinal cord and all the brain regions studied in aged rats when compared to young rats. Supplementation of aged rats with grape seed extract showed increased memory performance and declined reactive oxygen species production, decreased protein carbonyl levels and improved thiol levels. These findings demonstrated that grape seed extract enhanced the antioxidant status and decreased the incidence of free radical induced protein oxidation in aged rats thereby protecting the central nervous system from the reactive oxygen species.

Rejuvenation of antioxidant system in central nervous system of aged rats by grape seed extract.

Oxidative stress is considered as a major risk factor that contributes to age-related increase in lipid peroxidation and declined antioxidants in the central nervous system during aging. Grape seed extract, one of the bioflavonoid, is widely used for its medicinal properties. In the present study, we evaluated the role of grape seed extract on lipid peroxidation and antioxidant status in discrete regions of the central nervous system of young and aged rats. Male albino rats of Wistar strain were divided into four groups: Group I-control young rats, Group II-young rats treated with grape seed extract (100 mg/kg body weight) for 30 days, Group III-aged control rats and Group IV-aged rats supplemented with grape seed extract (100 mg/kg body weight) for 30 days. Age-associated increase in lipid peroxidation was observed in the spinal cord, cerebral cortex, striatum and the hippocampus regions of aged rats (Group III). Activities of antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase and levels of non-enzymic antioxidants like reduced glutathione, Vitamin C and Vitamin E were found to be significantly decreased in all the brain regions studied in aged rats when compared to young rats. However, normalized lipid peroxidation and antioxidant defenses were reported in the grape seed extract-supplemented aged rats. These findings demonstrated that grape seed extract enhanced the antioxidant status and decreased the incidence of free radical-induced lipid peroxidation in the central nervous system of aged rats.

Oxidative stress on mitochondrial antioxidant defense system in the aging process: role of DL-alpha-lipoic acid and L-carnitine.

BACKGROUND: Oxidative damage is hypothesized to accumulate throughout the lifetime of an organism, eventually giving rise to aging. The mitochondria may be the primary cellular source and target of endogenous ROS as they are produced as a normal byproduct of the electron transport system. METHODS: Male albino Wistar rats were used in this study. The animals were divided into 6 groups, each group consisting of 6 animals. Groups I, III, and V were young, middle-aged and aged control rats and Groups II, IV, and VI were treated with carnitine (300 mg/kg bw) and dl-alpha-lipoic acid (150 mg/kg bw), respectively. After the treatment period, the animals were sacrificed and the heart and skeletal muscle were removed for analysis. RESULT: There was a significant reduction in the levels of antioxidants in both middle-aged and aged rats whereas the thiobarbituric acid reactive substances were found to be increased. Co-supplementation of carnitine and lipoic acid improved the antioxidant status and brought down the levels of TBARS. CONCLUSION: Co-supplementation of lipoic acid with carnitine has a beneficial effect in reversing the age-related abnormalities seen in aging. This effect was associated with the decrease in free radical production and rise in antioxidant levels by carnitine and lipoic acid, thereby lowering oxidative stress.

Modulation of age-associated oxidative DNA damage in rat brain cerebral cortex, striatum and hippocampus by L-carnitine.

The free radical theory of cell aging may have significant relevance in the pathogenesis of a number of age-related neurological disorders. A large body of experimental evidence supports the existence of a relationship between genomic instability, DNA damage and aging. The age-associated accumulation of oxidative DNA damage is well documented in central nervous system. The decline of mitochondrial respiratory function and loss of normal cellular homeostasis as consequences of excessive accumulation of endogenous oxidative damages to DNA have long been indicated in the aging process. In the present study, age-associated alterations in the content of DNA and accumulation of oxidative DNA damage products such as 8-OHdG and DNA protein cross-links are mainly focused. In parallel, we have also investigated the salubrious effect of l-carnitine against oxidative DNA damage as it possesses energy and antioxidant improving properties. Our results thus reveal that L-carnitine has inhibiting effect on the accumulation of age-related oxidative DNA damage in various brain regions, viz. cerebral cortex, striatum and hippocampus.

Ascorbic acid and alpha-tocopherol as potent modulators of apoptosis on arsenic induced toxicity in rats.

Apoptosis or programmed cell death (PCD) is a genetically regulated cellular, physiological and biochemical suicidal mechanism that plays a crucial role in the development and defense of homeostasis, in which the cell participates in its own demise via a cascade of molecular interactions. PCD can be modulated by various stimuli including infectious agents or drugs. Arsenic is one among inducible toxic agent that triggers apoptosis via free radical generation. Since the generation of free radicals during the metabolism of arsenic is thought to be involved in arsenic toxicosis, understanding the deleterious effects caused by the ROS that attack the vital molecules like DNA has become important. The present work was conducted to evaluate the regulatory effect exerted by Vitamin C and Vitamin E upon the apoptotic process, which can be assessed by the presence of cells with apoptosis associated DNA breaks and characterize the role of TNF-alpha and caspase-3 in rats intoxicated with arsenic. Male albino rats of wistar strain (120-150 g) were used in this study and are further divided into seven groups. We observed that ascorbate and alpha-tocopherol selectively altered the extent of DNA damage by reducing TNF-alpha level and inhibiting the activation of caspase cascade, from these observations it is strongly believed that the present vitamins supplementation perspective, though observed in animal model, will have sustainable curative value among the already afflicted populations, neutralizing impact on freshly emerging arsenicosis scenario and possible proactive protection to those potentially susceptible to arsenicals exposure.

Age-dependent alterations in mitochondrial enzymes in cortex, striatum and hippocampus of rat brain -- potential role of L-Carnitine.

Mitochondria link the energy -- releasing activities of electron transport and proton pumping with the energy conserving process of oxidative phosphorylation to form ATP. A declined mitochondrial performance has been generally observed during aging. In the present investigation, the activities of tricarboxylic acid cycle enzymes such as isocitrate, alpha-ketoglutarate, succinate and malate dehydrogenases and electron transport complexes I-IV were measured in mitochondria isolated from brain regions like cortex, striatum and hippocampus of young and aged rats before and after L-Carnitine supplementation. All the three brain regions of aged rats showed decreased activities of isocitrate, alpha-ketoglutarate and succinate dehydrogenases, complexes I and IV when compared to control young rats. Striatum seems to be the most susceptible region when compared to hippocampus and cortex. L-Carnitine supplementation to aged rats reversed the activities of these enzymes to near normal whereas treatment to young rats did not show any significant alterations. These results confirm that L-Carnitine can alleviate the age-associated decline in the metabolic efficiency of mitochondria in all three brain regions under investigation.

Carnitine: a neuromodulator in aged rats.

A wide range of morphological and biochemical changes occur in the central nervous system with increasing age. L-carnitine, a naturally occurring compound, plays a vital role in fatty acid transport across the mitochondrial membrane. L-carnitine (300 mg/kg body wt/day) was administered intraperitoneally to young and old male Wistar rats for 7, 14, and 21 days. Carnitine, dopamine, epinephrine, and serotonin levels were assayed in discrete regions of the brain. Carnitine supplementation increased the levels of dopamine, epinephrine, and serotonin in the experimental animals in our study. Response to carnitine supplementation varied among the brain regions that have been studied. The regions rich in cholinergic neurons such as the cortex, hippocampus, and striatum showed more response after 21 days of carnitine treatment. The results of the present study suggest the role of L-carnitine as a neuromodulator and antiaging medication.