L-carnitine Treatment Research Articles

L-carnitine supplementation in culture media improves the pregnancy rate of in vitro produced embryos with sexed semen from Bos taurus indicus cows.

The in vitro embryo production industry in the actual world presents some difficulties related to low embryonic production rates, a problem that could be associated with in vitro culture conditions that differed from the in vivo (oviductal) conditions, mainly related to cytoplasmic lipid accumulation. L-carnitine is known as a modulator of β-oxidation in the developing embryo, as it has been demonstrated that it improves embryo quality without affecting the in vitro embryo production rate. The aim of the present work was to evaluate the effect of L-carnitine supplemented during the in vitro maturation and culture processes on the implantation rate of in vitro produced embryos. Supplementation with 3.8mM of L-carnitine was used during in vitro maturation, and later, during late in vitro culture, it was added at 1.5mM. A control group contained no L-carnitine supplementation. Bovine oocytes obtained by ultrasound-guided follicle aspiration from healthy Bos taurus indicus cows were matured, fertilized and cultured in vitro. Multiparous F1 (Bos taurus taurus × Bos taurus indicus) cows were used as recipients. Overall, 460 oocytes were processed in three independent replicates from in vitro maturation until day 8 of the in vitro culture. No significant difference was found between treatments of in vitro embryo production. However, pregnancy rate at days 45 and 72 was significantly higher in blastocysts derived from L-carnitine treatment (31.55 ± 9.78%) compared to the control group (18.68 ± 6.31%). In conclusion, addition of L-carnitine at 3.8mM and 1.5mM in the maturation, and culture medium after day 3 of in vitro production process, significantly improved pregnancy rate after embryo transfer.

Supplementing a skimmed milk-egg yolk-based extender with L-carnitine helps maintain the motility, membrane integrity and fertilizing capacity of chilled ram sperm.

This study examines the effect of L-carnitine (LC) on chilled ram semen stored for up to 96hr. Semen samples were collected, placed in a skimmed milk+6% egg yolk extender, pooled, aliquoted and diluted with the same extender supplemented with different LC concentration: 0 (control), 1mM (LC1), 2.5mM (LC2.5), 5mM (LC5), 7.5mM (LC7.5) or10mM (LC10). Sperm kinetics and membranes (plasma, acrosome and mitochondrial) were examined using the CASA system and triple fluorescence staining (PI/ PNA-FITC/Mitotracker). The progressive motility was greater (p<.05) with LC7.5 treatment than the control sperm at 96hr. The curvilinear velocity (p<.01) and the percentage of sperm with intact membranes (plasma/acrosome/mitochondria) (p<.01) were greater with all LC treatments than the control group at all times. Straight line velocity was greater (p<.01) with LC5 and LC7.5 treatments than the control group after 48hr. The LC5 group also returned lower ALH values (p<.05) than these seen for the control groups after 48hr. The fertilizing capacity of LC5 samples stored at 15°C for 2hr (LC5-15°C-2h) and at 5°C for 24hr (LC5-5°C-24h) was tested in three ewe groups via cervical fixed-time artificial insemination. In two groups, the fertilizing capacity of the LC5-5°C-24h was reduced (p<.001). In the remaining group, however, no significant difference was seen between the LC5-15°C-2h and LC5-5°C-24h sperm in this respect (pregnancy rates 52.4% versus 42.8%; p>.05). Overall, the present results suggest that supplementing skimmed milk-egg yolk-based extenders with LC has a positive effect on chilled sperm variables and fertilizing capacity.

Valproic acid poisoning: is L-carnitine infusion useful to alter pharmacokinetics or improve outcome?

Objectives: Valproic acid (VPA) poisoning causes life-threatening neurological, cardiovascular and metabolic disorders. L-carnitine is used to reverse toxicity without clinical evidence of effectiveness. We aimed to investigate the effects of L-carnitine treatment on VPA pharmacokinetics and its contribution to the patient prognosis.

Liver-Oriented Acute Metabolic Effects of A Low Dose of L-Carnitine under Fat-Mobilizing Conditions: Pilot Human Clinical Trial.

The acute metabolic effect of low dosages of L-carnitine under fat-mobilizing conditions was investigated. Healthy subjects (Study 1: n=5; Study 2: n=6) were asked to fast overnight. Then, 30 min of aerobic exercise on a cycle ergometer was performed after supplementation, followed by a 3.5-h sedentary recovery phase. The following ingestion patterns were used: Study 1 (i) noningestion, (ii) 750 mg of L-carnitine (LC), and (iii) 750 mg of LC+50 g of carbohydrate (CHO); Study 2 (iv) noningestion, (v) 500 mg of LC, (vi) 30 mg of CoQ10, and (vii) 500 mg of LC+30 mg of CoQ10. The energy expenditure (EE) and nonprotein respiratory quotient (npRQ) were measured during the pre-exercise, postexercise, and recovery periods. Serum free carnitine, acetylcarnitine, total carnitine (Study 1 and 2), and ketone bodies (Study 2) were measured. The 750 mg LC treatment significantly facilitated fat oxidation during the recovery phases (p<0.05) without elevating EE. The higher fat oxidation associated with LC was completely suppressed by CHO. CoQ10 affected neither npRQ nor EE. npRQ was significantly correlated with the serum total ketone bodies (R=-0.68, p<0.001) and acetylcarnitine (R=-0.61--0.70, p<0.001). The highest correlation was found between acetylcarnitine and total ketone bodies immediately after exercise (R=0.85, p<0.001). In conclusion, LC enhanced liver fat utilization and ketogenesis in an acute manner without stimulating EE under fat-mobilizing conditions.

The impact of L-carnitine Supplement on Semen Variables and the Levels of Sexual Hormones (Serum LH, FSH, Testosterone, and Inhibin) in Males with Infertility

Background: It had been estimated that tenth of partners had infertility, and in approximately half of these cases, the imperfection can be ascribed to male related causes. Fecundity in men necessitate regular functioning hypothalamus, pituitary gland, and testes axis. aberrant spermatogenesis is habitually incorporated to permuted serum gonadotropins and testosterone. L-carnitine is an supreme antioxidant existing in a lofty concentration in epididymal excretions. It affords liveliness for sperms to earn their dynamism in the epididymis.Aim: The study proposed to explore the effect of L-carnitine supplement on semen parameters, and sex hormones milieu in patients with primary or secondary infertility.Patients and Methods: A clinical trial conducted on a 58 patients(mean age± SD: 30.6 ± 6.07) treated with 2gm of L carnitine, which prescribed orally at a daily dose of 2gm a day in divided doses for 3 months. Before, and after the end of the L-carnitine treatment, semen analysis and serum levels of LH, FSH, Testosterone, and inhibin were performed.Results: The mean values of sperm count, total motility and normal morphology of and oligo-astheno-teratospermic were found notably changed (p<0.05) with 3 months carnitine supplement. The outcome of this trial exhibited that L-carnitine supplement can improve sperm concentration, and count, as well active motility. Additionally it has been noticed that the serum gonadotropin (FSH and LH) levels were noteworthy declined, while serum testosterone and inhibin levels were upraised in infertile males when compared with the levels before, the 3 months course of L-carnitine treatment.

Zinc oxide nanoparticles and l-carnitine effects on neuro-schistosomiasis mansoni induced in mice

Neuro-schistosomiasis can induce neurological symptoms and severe disability. Since the resistance against the chemotherapy "praziquantel" was reported, the aim of the present study was investigating the anti-neuro-schistosomal effects of ZnO nanoparticles and/or L-carnitine (as free radicals scavenger) on schistosome-infected mice, where technology of nanoparticles has come to the forefront in the medical diagnosis and therapeutic drug delivery. In the human body, nanoscale-sized particles can move freely and reveal unique biological, mechanical, electrical, and chemical properties. In the present study, mice were divided into five groups. The first group served as the non-infected control group. Groups II, III, IV, and V were infected with cercariae of Schistosoma mansoni. Mice of groups III and IV were treated with ZnO nanoparticles (5.6mg/kg b. wt.) and L-carnitine (500mg/kg b. wt.), respectively, after 47days post-infection. Finally, mice of the fifth group were injected with ZnO nanoparticles and after 1h, the mice were intraperitoneally injected with L-carnitine once daily for 5days. On day 52, post-infection mice of all groups were cervically decapitated. The treatment of ZnO nanoparticles and/or L-carnitine to schistosome-infected mice decreased brain oxidative stress parameters, where glutathione level and catalase activity were significantly increasedas compared to schistosome-infected group. On the contrary, the treatment decreased nitrite/nitrate, malondialdehyde, and reactive oxygen species levels significantly. In addition, ZnO nanoparticles and/or L-carnitine treatment restored DNA laddering profile and improved the brain histopathological impairments resulting from neuro-schistosomiasis. Finally, the ZnO nanoparticle treatment and the co-treatment of ZnO nanoparticles and L-carnitine revealed anti-neuro-schistosomal effects on the infected mice.

The improving effect of l-carnitine on larvae quality in early life stage of zebrafish (Danio rerio)

Our study aimed to improve the fish larval quality in terms of malformation and survival rate by l-carnitine (LC) supplementation in embryo culture media. Zebrafish embryos were immersed in a test solution contained 0, 0.5, and 1 mg L−1 LC followed the water bath method. The effect of LC on zebrafish embryo hatching, and larvae development, malformation and survival rates were observed at different time periods (6, 12, 24, 48, 72, 96, 120, 144, 168, 192 h) after fertilization. The results showed that LC (1 mg L-1) treatment promoted significantly the embryo hatching rate at 48 h after fertilization (50.00 ± 1.73%), and improved development rate at gastrula (6 h) (80.00 ± 5.77%), somatic (12h) (80.00 ± 5.77%) and pharyngula (24 h) (80.00 ± 5.77%) developmental life stages. In addition, improved body length at 48 h (1357.73 ± 1.00 um) and 72 h (1371.56 ± 34.72 um), decreased malformation rate (3.33 ± 0.58%), and increased survival rate at 12 h (80.00 ± 10.00%) (P ˂ 0.05).Therefore, LC had comprehensive effects on zebrafish larvae quality. Our research results could be applicable to aqua cultured species in fresh and marine hatcheries in order to decrease malformation and increase survival rates.

Effect of L-Carnitine on Amino Acid Metabolism in Elderly Patients Undergoing Regular Hemodialysis

Introduction: Among patients regularly undergoing hemodialysis, hypocarnitinaemia often develops as a consequence of inadequate dietary intake, reduced synthesis in the body, and considerable losses during hemodialysis. Objectives: To evaluate the effects of L-carnitine supplementation on patients with end-stage kidney disease (ESKD) who underwent hemodialysis. Methods: Thirty-one patients with ESKD, comprising 18 men and 13 women, with a median age of 72 (range 58–89) years, who underwent regular hemodialysis received treatment with L-carnitine for 1 year. The total and free carnitine, acylcarnitine, and amino acids (AA) levels before and after L-carnitine treatment were analyzed, and the blood biochemistry results and clinical profiles of the subjects were compared before and after treatment. Results: The median (interquartile range [IQR]) serum total and free carnitine and acylcarnitine levels significantly increased from 34.5 (28.2–44.3), 20.9 (15.8–27.6), and 14.1 (11.2–17.6) µmol/L, respectively to 407.4 (371.6–493.5), 270.2 (228.3–316.0), and 155.0 (136.1–168.5) µmol/L, respectively, after treatment (all p < 0.001). The median (IQR) blood valine, tyrosine, phenylalanine, and citrulline levels increased from 0.94 (0.80–1.09), 0.45 (0.39–0.55), 0.61 (0.56–0.79), and 1.04 (0.79–1.26) mg/dL, respectively to 1.24 (1.13–1.54), 0.76 (0.62–0.85), 0.90 (0.70–1.04), and 1.22 (0.92–1.39) mg/dL, respectively, following L-carnitine treatment (p < 0.001, p < 0.001, p = 0.002, and p = 0.030, respectively); however, the median (IQR) blood arginine level decreased from 0.20 (0.13–0.24) to 0.09 (0.06–0.14) mg/dL after treatment (p < 0.001). The median (IQR) percentage fractional shortening (41.5 vs. 41.9%; p = 0.012) and left ventricular ejection fraction (65.2 vs. 67.3%; p = 0.036) increased significantly following treatment. Conclusions: L-Carnitine increased the blood acylcarnitine levels, enhanced fatty acid metabolism, and affected AAs metabolism; this may be beneficial for energy production within the cardiac and skeletal muscles.

Effects of L-carnitine on embryo development of vitrified swamp buffalo oocytes following in vitro fertilization

The aim of this study was to evaluate the effect of L-carnitine (LC) supplemented in vitro maturation (IVM) medium on the cryotolerance and development of buffalo oocytes. Mitochondrial activity, reactive oxygen species (ROS) content, and lipid droplet distribution of vitrified-warmed buffalo oocytes were also observed. Oocytes were matured in IVM medium supplemented with 0, 0.3, 0.6, and 1.2 mg/mL LC and some of them were vitrified by the Cryotop® method. The highest survival, morula, and blastocyst rates were obtained with 0.6 mg/mL LC, irrespective of whether oocytes were fresh or vitrified-warmed. The density of active mitochondria in vitrified oocytes was significantly higher with 0.6 mg/mL LC than without LC treatment. In contrast, H2O2 levels and lipid droplet content were significantly lower following LC treatment than without it. In conclusion, supplementation with 0.6 mg/mL LC during IVM improves the buffalo oocytes’ survival rate and subsequent embryo development after in vitro fertilization. This may be linked to improved mitochondrial activity, enhanced β-oxidation, and reduced ROS levels.

L-carnitine reduces the adverse effects of ROS and up-regulates the expression of implantation related genes in in vitro developed mouse embryos

In vitro developed embryos are inevitably exposed to various reactive oxygen species (ROS) which may decrease the embryo’s competence in assisted reproductive technology (ART) procedures. Optimization of embryo culture media using antioxidant agents could help to improve embryo quality and could overcome failures in current ART. The aim of this study was to evaluate the effects of l-carnitine (LC), an enhancer of mitochondrial activity and free radical scavenger, in culture media on early embryo competence and expression of ErbB1 and ErbB4 implantation related genes. Two-cell mouse embryos were cultured in the following four conditions: 1. LC group in media containing LC; 2.H 2O2 group exposed to H2O2 for 30 min and then transferred into a simple media; 3.H2O2+LC group exposed to H2O2 for 30 min and then transferred into a simple media containing LC; 4.the control group kept throughout in simple media. All groups were allowed to develop until the blastocyst stage. ErbB1 and ErbB4 expression were evaluated by Real-time PCR and immunocytochemistry. The expression of Sirt3 gene was also evaluated. Intracellular ROS levels were examined by DCFH-DA fluorescence intensity. In order to assess the morphological quality of the embryos, ICM and OCM number blastocyst cells were evaluated by using Hoechst and propidium iodide (PI) staining. ErbB1, ErbB4, ROS levels and cell number were compared across all in vitro groups. Our data reveal that LC significantly increases ErbB1 and ErbB4 gene and protein expression with intracellular ROS levels and Sirt3 gene expression significantly decreased after LC treatment. It is worth noting that an elevated cell number was observed in the LC-treated group compared with the other groups suggesting increased viability and/or proliferation. Our findings suggest that the use of LC could be helpful to improve preimplantation embryo culture media through its effects in decreasing ROS levels and the increase of implantation-related genes.

Memory Impairment Induced by Chronic Psychosocial Stress Is Prevented by L-Carnitine.

IntroductionPsychosocial stress (STS) negatively influences memory. This might be associated to oxidative stress-induced progressive destruction of numerous brain structures and functions. L-carnitine (L-CAR) is a widely used antioxidant compound that is endogenously made in mammalian species. The current study investigated the effect of L-CAR on STS-induced memory impairment in the rat hippocampus.MethodsThe STS was induced using intruder model, where two rats were randomly switched from each one cage to another, once/day for 6 weeks. Concurrently, L-CAR (300mg/kg/day) was intraperitoneally administered for 6 weeks. After that, radial arm water maze (RAWM) was used to assess spatial learning memory in rats. Hippocampal biomarkers of oxidative stress, including thiobarbituric acid reactive substance (TBARs), oxidized glutathione (GSSG), reduced glutathione (GSH), glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD), and Brain-derived neurotrophic factor (BDNF) were examined.ResultsThe results showed impairment of short-term memory (P < 0.05) during STS, whereas L-CAR treatment protected against this effect. Furthermore, while no change was observed in GSH, GSSG, GPx, catalase, and SOD, L-carnitine normalized STS-induced reduction in the hippocampal BDNF levels and increase in TBARS levels.DiscussionChronic psychosocial stress-induced memory impairment was prevented via L-CAR administration, which could have been achieved via normalizing changes in lipid peroxidation (TBARs) and BDNF levels in the hippocampus.

L-carnitine supplementation during in vitro culture regulates oxidative stress in embryos from bovine aged oocytes

Aging oocytes undergo various molecular, cellular, and biochemical changes. Aging of oocytes results in reduced embryo developmental capacity and blastocyst quality, which is thought to be caused partly by the accumulation of reactive oxygen species (ROS). This study aimed to determine the effect of l-carnitine (LC) on the development of embryos formed from aged oocytes in vitro. The development and quality of the blastocysts in the LC-treated group were significantly higher than those in the untreated aged group after in vitro fertilization (IVF). In addition, after LC treatment, the level of intracellular ROS in aged group significantly decreased, and glutathione (GSH) levels significantly increased compared with those in the untreated aged group. There was no significant difference in the mitochondrial membrane potential among the three groups. Moreover, ROS could induce autophagy and LC3 antibody was widely used as a marker for detecting autophagy. The fluorescence intensity of LC3 in the aged group was significantly higher than that of LC3 in the LC-treated group. Furthermore, Real-time reverse transcriptase-polymerase chain reaction showed that the mRNA levels of antioxidation genes GPX4 and SOD1 were significantly higher in embryos from LC-treated group than in those from the untreated aged group. In summary, our results indicated that LC can improve the developmental capacity of embryos from aging oocytes in vitro by reducing oxidative stress.

The influence of l-carnitine on the expression of miRNAs in asthenospermia spermatozoa and the network regulation of the associated molecules.

l-carnitine is a natural compound that is indispensable for energy metabolism in mammals. The efficiency and safety of l-carnitine in improving sperm activity, enhancing epididymal function and treating male infertility has been widely acknowledged by clinicians. CircRNAs can regulate gene expression at the transcriptional or post-transcriptional level by serving as a molecular sponge of miRNAs with miRNA response elements. However, the detailed mechanism linking miRNA, circRNA and asthenospermia remains unclear. The present study demonstrated that hsa-miR-27b-3p, hsa-miR-151a-5p and hsa-miR-206 play an important role in the effects of l-carnitine treatment of the spermatozoa in asthenospermia patients. Furthermore, the target mRNAs of hsa-miR-206 were analysed by GO and KEGG. The results show that the target mRNAs of hsa-miR-206 may change the activity of ATP synthase and participate in the cAMP signalling pathway and the calcium signalling pathway, which may play an important role in sperm motility.

Carnitine supplementation improves metabolic flexibility and skeletal muscle acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trial.

BackgroundType 2 diabetes patients and individuals at risk of developing diabetes are characterized by metabolic inflexibility and disturbed glucose homeostasis. Low carnitine availability may contribute to metabolic inflexibility and impaired glucose tolerance. Here, we investigated whether carnitine supplementation improves metabolic flexibility and insulin sensitivity in impaired glucose tolerant (IGT) volunteers.MethodsEleven IGT- volunteers followed a 36-day placebo- and L-carnitine treatment (2 g/day) in a randomised, placebo-controlled, double blind crossover design. A hyperinsulinemic-euglycemic clamp (40 mU/m2/min), combined with indirect calorimetry (ventilated hood) was performed to determine insulin sensitivity and metabolic flexibility. Furthermore, metabolic flexibility was assessed in response to a high-energy meal. Skeletal muscle acetylcarnitine concentrations were measured in vivo using long echo time proton magnetic resonance spectroscopy (1H-MRS, TE=500 ms) in the resting state (7:00AM and 5:00PM) and after a 30-min cycling exercise. Twelve normal glucose tolerant (NGT) volunteers were included without any intervention as control group.ResultsMetabolic flexibility of IGT-subjects completely restored towards NGT control values upon carnitine supplementation, measured during a hyperinsulinemic-euglycemic clamp and meal test. In muscle, carnitine supplementation enhanced the increase in resting acetylcarnitine concentrations over the day (delta 7:00 AM versus 5:00 PM) in IGT-subjects. Furthermore, carnitine supplementation increased post-exercise acetylcarnitine concentrations and reduced long-chain acylcarnitine species in IGT-subjects, suggesting the stimulation of a more complete fat oxidation in muscle. Whole-body insulin sensitivity was not affected.ConclusionCarnitine supplementation improves acetylcarnitine formation and rescues metabolic flexibility in IGT-subjects. Future research should investigate the potential of carnitine in prevention/treatment of type 2 diabetes.

The capability of L-carnitine-mediated antioxidant on cock during aging: evidence for the improved semen quality and enhanced testicular expressions of GnRH1, GnRHR, and melatonin receptors MT 1/2.

Precise natural anti-oxidative compounds have facilitated the research of infertile gametes and the development of novel bio-therapeutics, especially the molecules that are based on the reduction of oxidative stress, such as L-carnitine (LC). In addition to, the defect in the functioning of sperm mitochondrial and the decreasing seminal antioxidant ability due to aging, its essential role in permitting the mitochondrial import and oxidation of long chain fatty acids is worthy. Therefore, current study was designed to investigate the effects of dietary LC on semen quality, seminal antioxidant activity, and their implications for the fertility in aged cocks for 12 wk. Supplementation of the feed with two different doses of LC (50 and 150mg/kg body weight/day) for 12 wk showed significantly increased in the reproductive activity of cock, in comparison to the control group. Seminal analysis showed that supplementation of LC significantly increased (P < 0.05) the sperm motility, concentration, livability, semen quality factor, seminal malondialdehyde concentration, catalase, and glutathione peroxidase activities. In addition, addition of LC significantly increased (P < 0.05) the plasma concentration of testosterone and prostaglandin E2 but posed no significant effect on the concentration of follicle-stimulating hormone. Furthermore, the findings of artificial insemination showed significant increased (P < 0.05) in the percentage of fertility in LC groups, while the percentage hatchability and mortality remained unchanged. Immunohistochemistry analysis revealed that LC significantly increased (P < 0.05) the testicular immunopositivity of MT1 and MT2. Moreover, the administration of LC to the aged cocks enhanced (P < 0.05) GnRH1 and GnRHR mRNA levels when compared with untreated cocks. The results of the present study suggest that LC treatment of aged cocks increases the seminal antioxidant enzymes and sexual hormones levels, which may improve the semen quality by increasing the expression of GnRH1 and melatonin receptors (MT1 and MT2) activities. Collectively, LC could be a suitable feed supplementation to increase reproductive activities through enhancing semen quality in aging cocks.

Cigarette Smoke Reduces Fatty Acid Catabolism, Leading to Apoptosis in Lung Endothelial Cells: Implication for Pathogenesis of COPD

Endothelial cell (EC) apoptosis contributes to cigarette smoke (CS)-induced pulmonary emphysema. Metabolism of glucose, glutamine, and fatty acid is dysregulated in patients with chronic obstructive pulmonary disease (COPD). Whether CS causes metabolic dysregulation in ECs leading to development of COPD remains elusive. We hypothesized that CS alters metabolism, resulting in apoptosis in lung ECs. To test this hypothesis, we treated primary mouse pulmonary microvascular ECs (PMVECs) with CS extract (CSE) and employed PMVECs from healthy subjects and COPD patients. We found that mitochondrial respiration was reduced in CSE-treated PMVECs and in PMVECs from COPD patients. Specifically, oxidation of fatty acids (FAO) was reduced in these cells, which linked to reduced carnitine palmitoyltransferase 1a (Cpt1a), an essential enzyme for carnitine shuttle. CSE-induced apoptosis was further increased when cells were treated with a specific Cpt1 inhibitor etomoxir or transfected with Cpt1a siRNA. L-Carnitine treatment augmented FAO but attenuated CSE-induced apoptosis by upregulating Cpt1a. CSE treatment increased palmitate-derived ceramide synthesis, which was reduced by L-carnitine. Although CSE treatment increased glycolysis, inhibiting glycolysis with 2-deoxy-d-glucose had no effects on CSE-mediated apoptosis in lung ECs. Conclusively, FAO reduction increases ceramide and apoptosis in lung ECs treated with CSE, which may contribute to the pathogenesis of COPD/emphysema.

Differential structural features in soleus and gastrocnemius of carnitine-treated cancer cachectic rats.

Muscle wasting is associated with chronic diseases and cancer. Elucidation of the biological mechanism involved in the process of muscle mass loss and cachexia may help identify therapeutic targets. We hypothesized that l-carnitine treatment may differentially revert muscle fiber atrophy and other structural alterations in slow- and fast-twitch limb muscles of rats bearing the Yoshida ascites hepatoma. In soleus and gastrocnemius of tumor-bearing rats (108 AH-130 Yoshida ascites hepatoma cells inoculated intraperitoneally) with and without treatment with l-carnitine (1 g/kg body weight for 7 days, intragastric), food intake, body and muscle weights, fiber typing and morphometry, morphological features, redox balance, autophagy and proteolytic, and signaling markers were explored. Levels of carnitine palmitoyl transferase were also measured in all the study muscles. l-Carnitine treatment ameliorated the atrophy of both slow- and fast-twitch fibers (gastrocnemius particularly), muscle structural alterations (both muscles), and attenuated oxidative stress, proteolytic and signaling markers (gastrocnemius). Despite that carnitine palmitoyl transferase-1 levels increased in both muscle types in a similar fashion, l-carnitine ameliorated muscle atrophy and proteolysis in a muscle-specific manner in cancer-induced cachexia. These data reveal the need to study muscles of different fiber type composition and function to better understand whereby l-carnitine exerts its beneficial effects on the myofibers in muscle wasting processes. These findings also have potential clinical implications, since combinations of various exercise and muscle training modalities with l-carnitine should be specifically targeted for the muscle groups to be trained.

Effect of addition of l-carnitine to media for oocyte maturation and embryo culture on development and cryotolerance of bovine embryos produced in vitro

The objective of these experiments was to determine the effect of l-carnitine during oocyte maturation or embryo culture on embryo development and cryosurvival. For Experiments 1–3, embryos were produced in vitro using abattoir-derived cumulus-oocyte complexes (COCs). At d 7 after insemination, embryo development was assessed, and blastocyst and expanded blastocyst stage embryos were harvested and subjected to controlled-rate freezing. Post-thaw cryosurvival was determined by re-expansion and hatching rates at 24, 48 and 72 h post-thaw. In Experiment 1, COCs were matured with or without 3.03 mM l-carnitine. There was no effect of l-carnitine supplementation during maturation on embryo development or post-thaw cryosurvival. In experiment 2, presumptive zygotes were cultured in medium supplemented with or without 5% (v/v) fetal bovine serum and l-carnitine at concentrations of 0.0, 0.75, 1.5 and 3.03 mM. There was no effect of l-carnitine treatment on embryo development, but embryos treated with l-carnitine had increased (P ≤ 0.05) post-thaw re-expansion rates, irrespective of concentration. In experiment 3, presumptive zygotes were cultured with or without 0.75 mM l-carnitine from d 1 to d 4, from d 4 to d 7 or for the entire culture period. There was no effect of l-carnitine during culture on embryo development or post-thaw cryosurvival, regardless of the timing of addition. In Experiment 4, COCs were harvested by ovum pick-up from virgin dairy heifers (n = 24) and subjected to in-vitro embryo production with presumptive zygotes cultured with or without 0.75 mM l-carnitine. At d 7 after insemination, morula and blastocyst stage embryos were harvested and subjected to controlled-rate freezing. Lactating Holstein cows (n = 102) were used as recipients and synchronized for timed embryo transfer. At d 7 after anticipated ovulation, a single embryo was thawed and transferred to the ipsilateral uterine horn of each recipient with a corpus luteum. Pregnancy was diagnosed at d 33, 44 and 72 of gestation. l-carnitine had no effect on the percentage of cows pregnant per embryo transfer (P/ET) after transfer of a frozen-thawed embryo. In conclusion, media supplementation with l-carnitine during in vitro embryo production can improve post-thaw cryotolerance as assessed in vitro but had no effect on P/ET after transfer of frozen-thawed embryos.

Untargeted Metabolomics Differentiates l-Carnitine Treated Septic Shock 1-Year Survivors and Nonsurvivors.

l-Carnitine is a candidate therapeutic for the treatment of septic shock, a condition that carries a ≥40% mortality. Responsiveness to l-carnitine may hinge on unique metabolic profiles that are not evident from the clinical phenotype. To define these profiles, we performed an untargeted metabolomic analysis of serum from 21 male sepsis patients enrolled in a placebo-controlled l-carnitine clinical trial. Although treatment with l-carnitine is known to induce changes in the sepsis metabolome, we found a distinct set of metabolites that differentiated 1-year survivors from nonsurvivors. Following feature alignment, we employed a new and innovative data reduction strategy followed by false discovery correction, and identified 63 metabolites that differentiated carnitine-treated 1-year survivors versus nonsurvivors. Following identification by MS/MS and database search, several metabolite markers of vascular inflammation were determined to be prominently elevated in the carnitine-treated nonsurvivor cohort, including fibrinopeptide A, allysine, and histamine. While preliminary, these results corroborate that metabolic profiles may be useful to differentiate l-carnitine treatment responsiveness. Furthermore, these data show that the metabolic signature of l-carnitine-treated nonsurvivors is associated with a severity of illness (e.g., vascular inflammation) that is not routinely clinically detected.

Effects of cell proliferation and apoptosis of L-carnitine combined with epirubicin on different human lung adenocarcinoma cells

Objective To investigate the effect of L-carnitine (LCNT) combined with epirubicin (EPI) on cell proliferation and apoptosis of two lung adenocarcinoma cell lines (GLC-82 and A549). Methods GLC-82 and A549 cells were divided into control group, EPI group, LCNT group and EPI+LCNT group, respectively. The cell proliferation rate was examined by MTT assay 24 h after the treatment, and the cell cycle and cell early apoptosis were analyzed by flow cytometry. The expression of P53 and Bcl-2 proteins were detected by Western Blot. Results Compared with the control group, the proliferation rate of GLC-82 and A549 cells was 37.56%(P 0.05) after 24 hours of 20.00 μg/ml LCNT treatment indicating LCNT could promote the proliferation of GLC-82 cells. Compared with the EPI group, EPI+LCNT had smaller inhibitory effect on the proliferation of GLC-82 cells, and the inhibition rate of the EPI+LCNT group was 12.14% lower than that of EPI group (P 0.05). Conclusions Comparing with the EPI, the combination of LCNT and EPI has less proliferation inhibition and apoptosis induction on GLC-82 cells, and without significant effect on A549 cells. LCNT can promote the proliferation of GLC-82 cells and block the cell cycle at G0/G1 phase. This mechanism may be related to down-regulation of P53 protein and up-regulation of Bcl-2 protein expression. Key words: Lung neoplasms; Adenocarcinoma; Cell proliferation; Cell apoptosis; L-carnitine; Epirubicin