共查询到20条相似文献,搜索用时 15 毫秒
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Cancer cachexia causes metabolic alterations with a marked effect on hepatic lipid metabolism. l-Carnitine modulates lipid metabolism and its supplementation has been proposed as a therapeutic strategy in many diseases.
In the present study, the effects of l-carnitine supplementation on gene expression and on liver lipid metabolism-related proteins was investigated in cachectic
tumour-bearing rats. Wistar rats were assigned to receive 1 g/kg of l-carnitine or saline. After 14 days, supplemented and control animals were assigned to a control (N), control supplemented
with l-carnitine (CN), tumour-bearing Walker 256 carcinosarcoma (TB) and tumour-bearing supplemented with l-carnitine (CTB) group. The mRNA expression of carnitine palmitoyltransferase I and II (CPT I and II), microsomal triglyceride
transfer protein (MTP), liver fatty acid-binding protein (L-FABP), fatty acid translocase (FAT/CD36), peroxisome proliferator-activated
receptor-alpha (PPAR-alpha) and organic cation transporter 2 (OCTN2) was assessed, and the maximal activity of CPT I and II
in the liver measured, along with plasma and liver triacylglycerol content. The gene expression of MTP, and CPT I catalytic
activity were reduced in TB, who also showed increased liver (150%) and plasma (3.3-fold) triacylglycerol content. l-Carnitine supplementation was able to restore these parameters back to control values (p < 0.05). These data show that l-carnitine preserves hepatic lipid metabolism in tumour-bearing animals, suggesting its supplementation to be of potential
interest in cachexia. 相似文献
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This study shows the effects of l-carnitine treatment on cell proliferation with hepa1c1c7 mouse cancer cells and NCTC 1469 normal cells. In an MTT assay,
l-carnitine increased the number of dead hepa1c1c7 cells, while there was no difference in the number of NCTC 1469 cells. mRNA
and protein levels of TNF-α, Fas, and caspase-8, which are closely related to cell apoptosis by a death ligand/receptor-dependent
apoptosis pathway, were increased by l-carnitine treatment. In addition, l-carnitine treatment regulated mitochondria-dependent apoptosis pathways by inducing the up-regulation of caspase-9 and caspase-3
and the down-regulation of Bcl-2 in hepa1c1c 7 cells. Taken together, the findings of this study have demonstrated that l-carnitine could induce apoptosis in hepa1c1c7 cells by regulating Fas ligands and inhibiting the expression of Bcl-2. These
results suggest that l-carnitine treatment could be related to both a mitochondrion-dependent and a death ligand/receptor-dependent apoptosis pathway
in hepa1c1c7 cells. Our results could give information for understanding the l-carnitine-induced apoptosis mechanism in some cancer cells. 相似文献
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Sitta A Barschak AG Deon M de Mari JF Barden AT Vanzin CS Biancini GB Schwartz IV Wajner M Vargas CR 《Cellular and molecular neurobiology》2009,29(2):211-218
Aims
l-Carnitine exerts an important role by facilitating the mitochondrial transport of fatty acids, but is also a scavenger of
free radicals, protecting cells from oxidative damage. Phenylketonuria (PKU), an inborn error of phenylalanine (Phe) metabolism,
is currently treated with a special diet consisting of severe restriction of protein-enriched foods, therefore potentially
leading to l-carnitine depletion. The aim of this study was to determine l-carnitine levels and oxidative stress parameters in blood of two groups of PKU patients, with good and poor adherence to
treatment. Methods Treatment of patients consisted of a low protein diet supplemented with a synthetic amino acids formula not containing Phe,
l-carnitine, and selenium. l-Carnitine concentrations and the oxidative stress parameters thiobarbituric acid reactive species (TBARS) and total antioxidant
reactivity (TAR) were measured in blood of the two groups of treated PKU patients and controls. Results We verified a significant decrease of serum l-carnitine levels in patients who strictly adhered to the diet, as compared to controls and patients who did not comply with
the diet. Furthermore, TBARS measurement was significantly increased and TAR was significantly reduced in both groups of phenylketonuric
patients relatively to controls. We also found a significant negative correlation between TBARS and l-carnitine levels and a significant positive correlation between TAR and l-carnitine levels in well-treated PKU patients. Conclusions Our results suggest that l-carnitine should be measured in plasma of treated PKU patients, and when a decrease of this endogenous component is detected
in plasma, supplementation should be considered as an adjuvant therapy. 相似文献
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Ribas GS Biancini GB Mescka C Wayhs CY Sitta A Wajner M Vargas CR 《Cellular and molecular neurobiology》2012,32(1):77-82
Propionic (PA) and methylmalonic (MMA) acidurias are inherited disorders caused by deficiency of propionyl-CoA carboxylase
and methylmalonyl-CoA mutase, respectively. Affected patients present acute metabolic crises in the neonatal period and long-term
neurological deficits. Treatments of these diseases include a protein restricted diet and l-carnitine supplementation. l-Carnitine is widely used in the therapy of these diseases to prevent secondary l-carnitine deficiency and promote detoxification, and several recent in vitro and in vivo studies have reported antioxidant
and antiperoxidative effects of this compound. In this study, we evaluated the oxidative stress parameters, isoprostane and
di-tyrosine levels, and the antioxidant capacity, in urine from patients with PA and MMA at the diagnosis, and during treatment
with l-carnitine and protein-restricted diet. We verified a significant increase of isoprostanes and di-tyrosine, as well as a significant
reduction of the antioxidant capacity in urine from these patients at diagnosis, as compared to controls. Furthermore, treated
patients presented a marked reduction of isoprostanes and di-tyrosine levels in relation to untreated patients. In addition,
patients with higher levels of protein and lipid oxidative damage, determined by di-tyrosine and isoprostanes levels, also
presented lower urinary concentrations of total and free l-carnitine. In conclusion, the present results indicate that treatment with low protein diet and l-carnitine significantly reduces urinary biomarkers of protein and lipid oxidative damage in patients with disorders of propionate
metabolism and that l-carnitine supplementation may be specially involved in this protection. 相似文献
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To investigate the mitochondrial decay and oxidative damage resulting from aging, the activities/kinetics of the mitochondrial
complexes were examined in the brains of young and old rats as well as in old rats fed R-α-lipoic acid plus acetyl-l-carnitine (LA/ALC). The brain mitochondria of old rats, compared with young rats, had significantly decreased endogenous
antioxidants and superoxide dismutase activity; more oxidative damage to lipids and proteins; and decreased activities of
complex I, IV and V. Complex I showed a decrease in binding affinity (increase in Km) for substrates. Feeding LA/ALC to old rats partially restored age-associated mitochondrial dysfunction to the levels of
the young rats. These results indicate that oxidative mitochondrial decay plays an important role in brain aging and that
a combination of nutrients targeting mitochondria, such as LA/ALC, could ameliorate mitochondrial decay through preventing
mitochondrial oxidative damage.
Special issue article in honor of Dr. Akitane Mori. 相似文献
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Türker Y Nazıroğlu M Gümral N Celik O Saygın M Cömlekçi S Flores-Arce M 《Biological trace element research》2011,143(3):1640-1650
The aim of this study was to investigate the possible protective role of selenium and l-carnitine on oxidative stress induced by 2.45-GHz radiation in heart of rat. For this purpose, 30 male Wistar Albino rats
were equally divided into five groups namely controls, sham controls, radiation-exposed rats, radiation-exposed rats treated
with intraperitoneal injections of sodium selenite at a dose of 1.5 mg/kg/day, and radiation-exposed rats treated with intraperitoneal
injections of l-carnitine at a dose of 1.5 mg/kg/day. Except for the controls and sham controls, the animals were exposed to 2.45-GHz radiation
during 60 min/day for 28 days. The lipid peroxidation (LP) levels were higher in the radiation-exposed groups than in the
control and sham control groups. The lipid peroxidation level in the irradiated animals treated with selenium and l-carnitine was lower than in those that were only exposed to 2.45-GHz radiation. The concentrations of vitamins A, C, and
E were lower in the irradiated-only group relative to control and sham control groups, but their concentrations were increased
in the groups treated with selenium- and l-carnitine. The activity of glutathione peroxidase was higher in the selenium-treated group than in the animals that were
irradiated but received no treatment. The erythrocyte-reduced glutathione and β-carotene concentrations did not change in
any of the groups. In conclusion, 2.45-GHz electromagnetic radiation caused oxidative stress in the heart of rats. There is
an apparent protective effect of selenium and l-carnitine by inhibition of free radical formation and support of the antioxidant redox system. 相似文献
10.
Acetyl-l-carnitine as a precursor of acetylcholine 总被引:2,自引:0,他引:2
Synthesis of [3H]acetylcholine from [3H]acetyl-l-carnitine was demonstrated in vitro by coupling the enzyme systems choline acetyltransferase and carnitine acetyltransferase. Likewise, both [3H] and [14C] labeled acetylcholine were produced when [3H]acetyl-l-carnitine andd-[U-14C] glucose were incubated with synaptosomal membrane preparations from rat brain. Transfer of the acetyl moiety from acetyl-l-carnitine to acetylcholine was dependent on concentration of acetyl-l-carnitine and required the presence of coenzyme A, which is normally produced as an inhibitory product of choline acetyltransferase. These results provide further evidence for a role of mitochondrial carnitine acetyltransferase in facilitating transfer of acetyl groups across mitochondrial membranes, thus regulating the availability in the cytoplasm of acetyl-CoA, a substrate of choline acetyltransferase. They are also consistent with a possible utility of acetyl-l-carnitine in the treatment of age-related cholinergic deficits. 相似文献
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A novel enzyme, l-carnitine amidase, was purified about 140-fold from a newly screened microorganism (DSM 6320) to yield a homogeneous protein. The native enzyme has a molecular mass of 125 kDa (gel filtration) and consists of two identical subunits as determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Edman degradation. The pH optimum was found around pH 8.5. Out of 60 chemicals tested as substrates (amides of various aliphatic and aromatic acids, nitriles, amino acid amides and dipeptide amides) the amidase hydrolysed only l-carnitine amide. The Michaelis constant (Km) was found to be 11.6 mm, and the pure protein had a specific activity of 328 units/mg. Complex kinetics were observed with the racemic mixture of d,l-carnitine amide as starting material during enzymatic hydrolysis.
Correspondence to: M.-R. Kula 相似文献
12.
Giuseppe Arienti Maria Teresa Ramacci Franco Maccari Angela Casu Lanfranco Corazzi 《Neurochemical research》1992,17(7):671-675
The fluorescence anisotropy (r) of diphenylhexatriene (DPH) was measured in different preparations (bovine spinal cord phosphatidylserine liposomes, rat brain microsomes, liposomes made with rat brain microsomal lipid having different phospholipid:cholesterol ratios) at temperatures ranging from 10° to 55°C. Phosphatidylserine liposomes exhibited an exponential relationship of rversus temperature, whereas the relationship shown by microsomes and liposomes prepared with microsomal lipid extracts was a linear one. The removal of protein and high phospholipid:cholesterol ratios decreased the slope of the lines (fluidity increased), although the intercept was unaffected. This means that differences were better appreciated at high temperatures and were well evident at 37°C. Acetyl-l-carnitine decreased r in rat brain microsomes and in liposomes made with microsomal lipids with different phospholipid:cholesterol ratios. The fluidifying effect of acetyl-l-carnitine was mild but statistically significant and could explain, at least in part, the data reported in the literature of acetyl-l-carnitine acting on some parameters affected by ageing. Besides, acetyl-l-carnitine seemed to oppose the changes of viscosity due to lipid peroxidation, which has been reported to increase in ageing and dementia.l-carnitine shares the properties of its acetyl ester, but only in part.Abbreviations DPH
diphenylhexatriene
- HEPES
4-(2-hydroxyethyl-l-piperazineethansulfonic) acid
- r
fluorescence anisotropy
- SHB
sucrose-HEPES-buffer (0.32 M sucrose, 2 mM HEPES, pH 7.0) 相似文献
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In our previous studies we have found both an increase of lipid peroxidation damage (expressed as levels of thiobarbituric acid-reactive substances) in brain and plasma lactate concentration in 21-day-old rats after a 30-min exposure to hypobaric hypoxia. Pretreatment of rats with l-carnitine decreased both parameters. The aim of our present study was to determine if the l-carnitine-dependent decrease of plasma lactate could be due to a modification of lactate dehydrogenase (LDH) activity. We followed brain and blood serum LDH activity of 14-, 21- and 90-day-old Wistar rats. We found an increase of brain LDH activity with age. However, we did not observe any significant differences in LDH activity after exposure to hypobaric hypoxia or l-carnitine pretreatment. In contrast to brain, serum LDH activity did not show any clear age-dependence. The hypoxia exposure increased LDH activity of 21-day-old rats only. Pretreatment of rats with l-carnitine decreased serum LDH activity of 21- and 90-day-old rats probably due to membrane stabilizing role of l-carnitine. In conclusions, acute hypobaric hypoxia and/or l-carnitine pretreatment modified serum but not brain LDH activity. 相似文献
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Summary Enterobacteria, especially Escherichia coli, Salmonella typhimurium and Proteus vulgaris, are capable of forming l(-)-carnitine by hydration of the double bond of crotonobetaine under anaerobic conditions. The carnitine hydrolyase is an inducible cytosolic enzyme which catalyses either the dehydration of l-carnitine or the hydration of crotonobetaine. In growing cultures, the addition of fumarate to a complex or minimal medium stimulated l-carnitine synthesis by diminishing the reduction of crotonobetaine to -butyrobetaine. However, l-carnitine synthesis was repressed after addition of nitrate or under aerobic conditions. If the carnitine hydrolyase was induced by l-carnitine or crotonobetaine, these respiratory chain electron acceptors did not impair carnitine formation by resting cells, indicating an epigenetical regulation of carnitine synthesis. Using this bacterial pathway for the biosynthesis of l-carnitine, conditions for producing a high yield are described. The method has some advantages in comparison with other biochemical or microbiological procedures for the production of l-carnitine.Dedicated to Professor Dr. H.-J. Rehm on the occasion of his 60th birthday 相似文献
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Hermann Seim Heinz Löster Reiner Claus Hans-Peter Kleber Erich Strack 《Archives of microbiology》1982,132(1):91-95
In view of the development of al-carnitine deficiency, the metabolism ofl-carnitine and structure-related trimethylammonium compounds was studied inSalmonella typhimurium LT2 by means of thin-layer chromatography (TLC).l-Carnitine, crotonobetaine and acetyl-l-carnitine stimulated the anaerobic growth in a complex medium significantly. The stimulation depended on the formation of -butyrobetaine. The reduction ofl-carnitine proceeded in two steps: (1) Dehydration of thel-carnitine to crotonobetaine, (2) hydrogenation of crotonobetaine to -butyrobetaine. The reduction of crotonobetaine was responsible for the growth stimulation. Terminal electron acceptors of the anaerobic respiration such as nitrate and trimethylamine N-oxide, but not fumarate, suppressed the catabolism ofl-carnitine completely. Glucose fermentation, too, inhibited the reduction ofl-carnitine but optimal growth with a high carnitine catabolism was achieved byd-ribose. The esters of carnitine with medium- and long-chain fatty acids inhibited the growth considerably because of their detergent properties.Abbreviations TLC
thin-layer chromatography 相似文献
16.
The current study was undertaken to investigate the protective role of melatonin (MEL) and acetyl-l-carnitine (ALC) against dexamethasone (DM)-induced neurotoxicity. Adult female rats (60) were divided into: (1) control group,
(2) DM-treated group, (3) MEL-treated group, (4) ALC-treated group, (5) MEL- and DM-treated, and (6) ALC- and DM-treated group.
Serum acetylcholinesterase (AchE) activity, malondialdehyde (MDA), nitric oxide (NO) level, catalase (CAT), superoxide dismutase
(SOD) and glutathione-S-transferase (GST) activities were estimated. Gene expression of the prooxidants (NO synthases NOS-1, NOS-2 and heme oxygenases
HO-1, HO-2) and antioxidant enzyme (GST-P1) as well as deoxyribonucleic acid (DNA) fragmentation analysis of brain tissue
were investigated. Histological examination of the brain tissue was carried out. DM administration caused significant increase
in serum AchE activity, MDA and NO levels accompanied with significant decrease in the antioxidant enzymes activity. Pretreatment
with MEL or ALC prior DM has been found to reverse all the former parameters. On the genetic level, DM administration significantly
increased the expression level of NOS-1, NOS-2, HO-1, and HO-2 messenger ribonucleic acids (mRNAs) and decreased that GST-P1-mRNA
in brain tissue. Also, DM produced DNA fragmentation in brain tissue. Treatment with MEL or ALC prior DM administration tend
to normalize the above mentioned parameters. These results were documented by the histological examination of brain tissue.
The present study suggests that oxidative stress is involved in the pathogenesis of DM-induced neurotoxicity. The inhibition
of oxidative stress via stimulation of the antioxidant enzymes by MEL and ALC pretreatment plays a central protective role
in modulation of neurotoxicity induced by DM. 相似文献
17.
Abazar Yari Mohammad Hossein Asadi Hossein Bahadoran Hossein Dashtnavard Hossein Imani Mohammad Reza Naghii 《Biological trace element research》2010,137(2):216-225
In this study, the effects of cadmium toxicity and the protective effects of l-carnitine on spermatogenesis in Sprague–Dawley rat were evaluated. Animals were subdivided into five groups. Cadmium chloride
(1-mg/kg body weight) was injected intraperitoneally during 16 days at intervals of 48 h between subsequent treatments. l-Carnitine (500 mg/kg b.w., IP) was pretreated in both of control and cadmium-injected rats. Animals were killed on day 17
after the first treatment. The left cauda epididymis was removed and immediately immersed into Hank’s balanced salt solution
for evaluation of sperm count and viability. Following contamination with cadmium, a decrease in the number and viability
of cauda epididymis sperm, the number of cell proliferation, and Johnsen Scores in the seminiferous tubules was observed.
Consequently, l-carnitine treatment caused an increase in the number and viability of cauda epididymis sperm, the number of cell proliferation,
and Johnsen Scores in the cadmium-induced group. 相似文献
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Hedieh Keshavarz-Bahaghighat Mohammad Reza Sepand Mohammad Hossein Ghahremani Mehdi Aghsami Nima Sanadgol Ameneh Omidi Vida Bodaghi-Namileh Omid Sabzevari 《Biological trace element research》2018,184(2):422-435
Augmentation of mitochondrial oxidative stress through activating a series of deadly events has implicated as the main culprit of arsenic toxicity and therapeutic approaches based on improving mitochondrial function hold a great promise for attenuating the arsenic-induced toxicity. Acetyl-l-carnitine (ALC) through balancing the coenzyme A (CoA)/acyl-CoA ratio plays an important role in mitochondrial metabolism and thereby can help protect hippocampal neurons from oxidative damage. In the present study, we aimed to explore the effect of arsenic interactions on the mitochondrial function in the hippocampus of rats. Rats were randomly divided into five groups of control (distilled water), sodium arsenite (NaAsO2, 20 mg/kg), and co-treatment of NaAsO2 with various doses of ALC in three groups (100, 200, 300 mg/kg) and were treated orally for 21 consecutive days. Our results point out that arsenic exposure caused oxidative stress in rats’ hippocampus, which led to the reactive oxygen species (ROS) generation, mitochondrial swelling, the collapse of the mitochondrial membrane potential, and release of cytochrome c. It also altered Bcl-2/Bax expression ratio and increased caspase-3 and caspase-9 activities. Furthermore, arsenic exposure via activation of NF-κB and microglia increased inflammation. ALC could concentration-dependently counteract the arsenic-induced oxidative stress, modulate the antioxidant defense capacity, and improve mitochondrial functions. In addition, ALC decreased the expression of both death-associated proteins and of inflammatory markers. These findings indicate that ALC improved the arsenic-induced hippocampal mitochondrial dysfunction which underlines the importance of ALC in providing a possible therapeutic strategy for the prevention of arsenic-induced neurodegeneration. 相似文献
19.
J. M. Obón J. R. Maiquez M. Cánovas H.-P. Kleber J. L. Iborra 《Applied microbiology and biotechnology》1999,51(6):760-764
The use of a biological procedure for l-carnitine production as an alternative to chemical methods must be accompanied by an efficient and highly productive reaction
system. Continuous l-carnitine production from crotonobetaine was studied in a cell-recycle reactor with Escherichia coli O44 K74 as biocatalyst. This bioreactor, running under the optimum medium composition (25 mM fumarate, 5 g/l peptone), was
able to reach a high cell density (26 g dry weight/l) and therefore to obtain high productivity values (6.2 g l-carnitine l−1 h−1). This process showed its feasibility for industrial l-carnitine production. In addition, resting cells maintained in continuous operation, with crotonobetaine as the only medium
component, kept their biocatalytic capacity for 4 days, but the biotransformation capacity decreased progressively when this
particular method of cultivation was used.
Received: 10 December 1998 / Received revision: 19 February 1999 / Accepted: 20 February 1999 相似文献
20.
Joanna Saluk-Juszczak Beata Olas Barbara Wachowicz Rafal Glowacki Edward Bald 《Cell biology and toxicology》2010,26(4):355-365
The oxidative stress induced by acute exertion may interfere with blood platelet activation. The beneficial effect of l-carnitine (γ-trimethylamino-β-hydroxybutyric acid) on oxidative stress in blood platelets has not been fully investigated;
however, different studies indicate that this compound modulates platelet functions. The aim of our study was to assess the
effects of l-carnitine on platelet activation and oxidative/nitrative protein damage (determined by the levels of protein carbonyl groups,
thiol groups, and 3-nitrotyrosine residues) in resting blood platelets or platelets treated with peroxynitrite (ONOO−, a strong physiological oxidant) in vitro. We also investigated the effects of l-carnitine on the level of platelet glutathione and on the formation of superoxide anion radicals ( O2 - · ) \left( {{\hbox{O}}_2^{ - \bullet }} \right) , lipid peroxidation measured by thiobarbituric acid reactive substances (TBARS) in blood platelets stimulated by thrombin
(a strong physiological agonist), and platelet aggregation induced by adenosine diphosphate (a strong physiological stimulator).
We have observed that carnitine decreases platelet activation (measured by platelet aggregation, the generation of O2 - · {\hbox{O}}_2^{ - \bullet } , and TBARS production). Moreover, our results in vitro demonstrate that carnitine may protect against oxidation of thiol
groups induced by ONOO−. Thus, carnitine may have some protectory effects against oxidative changes induced in blood platelets. 相似文献