l-Carnitine l-tartrate (LCLT) and dehydroepiandrosterone sulfate (DHEAS) affect red and white blood cells in aged Sprague–Dawley rats (original) (raw)
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Proceedings of the National Academy of Sciences, 2002
Mitochondrial-supported bioenergetics decline and oxidative stress increases during aging. To address whether the dietary addition of acetyl-L-carnitine [ALCAR, 1.5% (wt͞vol) in the drinking water] and͞or (R)-␣-lipoic acid [LA, 0.5% (wt͞wt) in the chow] improved these endpoints, young (2-4 mo) and old (24 -28 mo) F344 rats were supplemented for up to 1 mo before death and hepatocyte isolation. ALCAR؉LA partially reversed the age-related decline in average mitochondrial membrane potential and significantly increased (P ؍ 0.02) hepatocellular O 2 consumption, indicating that mitochondrial-supported cellular metabolism was markedly improved by this feeding regimen. ALCAR؉LA also increased ambulatory activity in both young and old rats; moreover, the improvement was significantly greater (P ؍ 0.03) in old versus young animals and also greater when compared with old rats fed ALCAR or LA alone. To determine whether ALCAR؉LA also affected indices of oxidative stress, ascorbic acid and markers of lipid peroxidation (malondialdehyde) were monitored. The hepatocellular ascorbate level markedly declined with age (P ؍ 0.003) but was restored to the level seen in young rats when ALCAR؉LA was given. The level of malondialdehyde, which was significantly higher (P ؍ 0.0001) in old versus young rats, also declined after ALCAR؉LA supplementation and was not significantly different from that of young unsupplemented rats. Feeding ALCAR in combination with LA increased metabolism and lowered oxidative stress more than either compound alone.
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2008
In mammals, during the aging process, an atrophy of the muscle fibers, an increase in body fat mass, and a decrease in skeletal muscle oxidative capacities occur. Compounds and activities that interact with lipid oxidative metabolism may be useful in limiting damages that occur in aging muscle. In this study, we evaluated the effect of L-carnitine and physical exercise on several parameters related to muscle physiology. We described that supplementing old rats with Lcarnitine at 30 mg/kg body weight for 12 weeks (a) allowed the restoration of L-carnitine level in muscle cells, (b) restored muscle oxidative activity in the soleus, and (c) induced positive changes in body composition: a decrease in abdominal fat mass and an increase in muscle capabilities without any change in food intake. Moderate physical exercise was also effective in (a) limiting fat mass gain and (b) inducing an increase in the capacities of the soleus to oxidize fatty acids.
Annals of the New York Academy of Sciences, 2004
L-carnitine and acetyl-L-carnitine (ALC) are both used to improve mitochondrial function. Although it has been argued that ALC is better than l-carnitine in absorption and activity, there has been no experiment to compare the two compounds at the same dose. In the present experiment, the effects of ALC and L-carnitine on the levels of free, acyl, and total L-carnitine in plasma and brain, rat ambulatory activity, and biomarkers of oxidative stress are investigated. Aged rats (23 months old) were given ALC or L-carnitine at 0.15% in drinking water for 4 weeks. L-carnitine and ALC were similar in elevating carnitine levels in plasma and brain. Both increased ambulatory activity similarly. However, ALC decreased the lipid peroxidation (malondialdehyde, MDA) in the old rat brain, while L-carnitine did not. ALC decreased the extent of oxidized nucleotides (oxo8dG/oxo8G) immunostaining in the hippocampal CA1 and cortex, while L-carnitine did not. ALC decreased nitrotyrosine immunostaining in the hippocampal CA1 and white matter, while L-carnitine did not. In conclusion, ALC and L-carnitine were similar in increasing ambulatory activity in old rats and elevating carnitine levels in blood and brain. However, ALC was effective, unlike L-carnitine, in decreasing oxidative damage, including MDA, oxo8dG/oxo8G, and nitrotyrosine, in old rat brain. These data suggest that ALC may be a better dietary supplement than L-carnitine.
Mutagenesis, 2005
Literature data indicate L-carnitine (LC), a transmitochondrial carrier of acetyl and long chain groups, as an agent possessing protective effects against oxidative stress in mammalian cells. However, the major factor involved in the protective mechanism is not known. The protection activity exerted by this agent against reactive oxygen species induced by hydrogen peroxide (H 2 O 2 ) and t-butylhydroperoxide (t-butyl-OOH) treatment in isolated human peripheral blood lymphocytes (PBLs) has been studied. Human lymphocytes cells were isolated and pre-incubated with 5 mM LC before H 2 O 2 (100 mM) and t-butyl-OOH (400 mM) treatment. The protective effect of LC on treated PBLs was measured by single cell gel electrophoresis and the analysis of chromosomal aberrations. Results show that LC treated cells exhibited a significant decrease in the number of oxidative induced single-strand breaks and chromosomal aberrations.
Annals of the New York Academy of Sciences, 2004
Carnitine and its congeners may regulate the immune networks, and their influence on functions of immune cells predominantly or exclusively relies on carnitine-dependent energy production from fatty acids. A reduced pool of carnitines has been demonstrated in either serum or tissues, or both, from patients with a wide spectrum of disorders characterized by unregulated or impaired immune responses ranging from sepsis syndrome to systemic sclerosis, infection with human immunodeficiency virus, and chronic fatigue syndrome. Furthermore, experimental studies have consistently reported that the deranged immune responses and the less efficient inflammation towards infectious organisms associated with aging may be enhanced or modulated by treatment with carnitines. There is also evidence that carnitine deprivation could adversely affect the course of the sepsis syndrome, at least in experimental models, and preliminary studies suggest that carnitine deficiency is ultimately implicated in the pathophysiology of endotoxin-mediated multiple organ failure. Several data indicate that carnitine deficiency is a contributing factor to the progression of infection with human immunodeficiency virus, and carnitine therapy in those patients could counteract the unregulated process of lymphocyte apoptosis and improve CD4 counts. Some case reports have suggested the use of carnitine for the treatment of the severe lactic acidosis that complicates in some patients the use of reverse transcriptase inhibitors.
Food and Chemical Toxicology, 2019
This study investigated the effects of L-carnitine supplementation on carnitine levels, oxidative stress and apoptotic markers in the stomach, kidney, liver and testis tissues in adult rats. Rats were randomized to control and L-carnitine supplemented (LCAR) groups. Control group received distilled water for 7 months by intragastric gavage and the LCAR group was given 50 mg/kg/day L-carnitine via intragastric intubation for the same period. L-carnitine concentrations and caspase-3 activity were measured by fluorometric methods while cleaved caspase-3 was determined by Western blot analysis. Bcl-2 associated X protein (Bax) and B-cell lymphoma/leukemia-2 (Bcl-2) were quantified by enzyme immunoassay and Western blot analysis. Oxygen/nitrogen species (ROS/RNS) and total antioxidant capacity (TAC) were analyzed by colorimetric assay. Tissue L-carnitine concentrations were significantly increased in the LCAR group compared to controls. Anti-apoptotic Bcl-2 levels were significantly increased while pro-apoptotic Bax was significantly decreased in LCAR group rats compared to controls. Tissue caspase-3 was significantly alleviated in the LCAR group compared to controls. L-carnitine supplementation increased TAC and decreased ROS/RNS generation in the kidney, liver, stomach and testis tissues compared to controls. Obtained data suggests that L-carnitine supplementation can potentially be used to lessen both oxidative and apoptotic progression in peripheral organs.
Annals of the New York Academy of Sciences, 1998
We show that mitochondrial function in the majority of hepatocytes isolated from old rats (24 mo) is significantly impaired. Mitochondrial membrane potential, cardiolipin levels, respiratory control ratio, and overall cellular O 2 consumption decline, and the level of oxidants increases. To examine whether dietary supplementation of micronutrients that may have become essential with age could reverse the decline in mitochondrial function, we supplemented the diet of old rats with 1% (w/v) acetyl-L-carnitine (ALCAR) in drinking water. ALCAR supplementation (1 month) resulted in significant increases in cellular respiration, mitochondrial membrane potential, and cardiolipin values. However, supplementation also increased the rate of oxidant production, indicating that the efficiency of mitochondrial electron transport had not improved. To counteract the potential increase in oxidative stress, animals were administered N-tert-butyl-=-phenyl-nitrone (30 mg/kg) (PBN) with or without ALCAR. Results showed that PBN significantly lowered oxidant production as measured by 2,7-dichlorofluorescin diacetate (DCFH), even when ALCAR was coadministered to the animals. Thus, dietary supplementation with ALCAR, particularly in combination with PBN, improves mitochondrial function without a significant increase in oxidative stress.
Chemico-biological Interactions, 2004
The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS), considered as the pathogenic agent of many diseases and aging. l-Carnitine (4-N-trimethylammonium-3-hydroxybutric acid) plays an important role in transport of fatty acid from cytoplasm to mitochondria for energy production. Previous studies in our laboratory reported l-carnitine as a free radical scavenger in aged rats. In the present study we focused the effect of l-carnitine on the activities of electron transport chain in young and aged rats. The activities of electron transport chain complexes were found to be significantly decreased in aged rats when compared to young control rats. Supplementation of carnitine to young and aged rats for 14 and 21 days improved the electron transport chain complexes levels in aged rats when compared with young rats in duration dependent manner. No significant changes were observed in young rats. Our result suggested that l-carnitine improved the activities of electron transport chain enzymes there by improving the energy status in aged rats.
Clinical Nutrition, 2005
Background: Mitochondria are central to energy production and are therefore fully integrated into the rest of the cell's physiological responses to stress. The agerelated decline of capacity of each cell to manufacture energy (as ATP) is due to the progressive loss of structural integrity of mitochondria. It is apparent that as the body ages, the cells become less and less able to maintain threshold levels of cellular energy production. Methods: In the present study we have evaluated the efficacy of carnitine, a mitochondrial metabolite and lipoic acid, a potent antioxidant on the activities of the tri carboxylic acid (TCA) cycle enzymes like succinate dehydrogenase, malate dehydrogenase, a-ketoglutarate dehydrogenase, Isocitrate dehydrogenase and electron transport complex I-IV in young and aged heart mitochondria. Result: We observed that there was an age-dependent decrement in the levels of the TCA cycle enzymes and electron transport chain complexes. Supplementation of carnitine (300 mg/kg bw/day) and lipoic acid (100 mg/kg bw/day) for 30 days brought the activities of these enzymes to almost near normal levels. Conclusion: These findings suggest that the combination of these drugs raises the mitochondrial energy producing capabilities by reversing the age-associated decline in mitochondrial enzyme activities and thereby protecting mitochondria from aging.