L-Carnitine拮抗培养心肌细胞缺氧/复氧损伤

目的 探讨L Carnitine对心肌细胞缺氧 /复氧损伤的防护作用及其可能的机制。方法 以原代培养新生鼠心肌细胞建立缺氧 /复氧损伤模型 ,观察不同剂量L Carnitine处理后细胞增殖活性、凋亡细胞百分率及DNA断片化率 ,作为反映L Carnitine对心肌细胞缺氧 /复氧损伤防护作用及其机制的指标。结果 在 5～ 5 0 0 0nmol/L范围内 ,L Carnitine预处理对培养心肌细胞缺氧 /复氧损伤均显示保护效应 ;在 5、5 0及 5 0 0nmol/L时均显著降低DNA断片化率 ;L Carnitine在 5 0nmol/L时与单纯缺氧 /复氧组比较可显著降低凋亡细胞百分率。结论 缺氧 /复氧对心肌细胞的影响之一是可诱导心肌细胞凋亡 ;L Carnitine对培养心肌细胞培养缺氧/复氧损伤具有防护作用 ,其机制可能与抑制缺氧 /复氧诱导细胞凋亡有关。

The Protective Effect of L-carnitine on Ischemia-reperfusion Heart

To investigate the protective effect of L-carnitine on myocardial ischemia-reperfusion injury in rat heart,all harvested isolated hearts were perfused on Langendorff apparatus with oxygenized K-H solution for 20 min. The hearts were then exposed to ischemia for 30 min. Following the ischemia the hearts were re-perfused with K-H solution for 120 min to serve as the control group A. Either 5 or 10 mmol/L of L-carnitine was added into the K-H solution for 20 min at the beginning of reperfusion to generate group B and group C, respectively. The derivatives of the intraventricular pressure curve （DP/DT）, left ventricular developed pressure （LVDP）, and coronary flux were monitored during the entire experiment. The levels of ATP, hepatin, malondialdehyde （MDA）, and superoxide dismutase （SOD） in tissue, and lactic dehydrogenase （LDH）, creatine phosphate kinase （CPK）, malondialdehyde （MDA）, and superoxide dismutase （SOD） concentration in the coronary efflux were all measured. Compared with the control group, the treatment with L-carnitine resulted in better results, i. e. , higher DP/DTmax and LVDP. At the same time, ventricular fibrillation was reduced, and the levels of ATP, hepatin and SOD were all elevated. However, the concentrations of MDA, CPK and LDH were all reduced. In conclusion, L-carnitine has a protective effect on ischemia-reperfusion injury, which is partly due to its prevention of energy loss and its antioxidant activity.

Beneficial effect of butyrate, Lactobacillus casei and L-carnitine combination in preference to each in experimental colitis

AIM: To investigate the beneficial effect of the combination of butyrate, Lactobacillus casei, and L-carnitine in a rat colitis model.METHODS: Rats were divided into seven groups. Fourgroups received oral butyrate, L-carnitine, Lactobacillus casei and the combination of three agents for 10 consecutive days. The remaining groups included negative and positive controls and a sham group. Macroscopic, histopathological examinations, and biomarkers such as tumor necrosis factor-alpha(TNF-α) and interlukin-1β(IL-1β), myeloperoxidase(MPO), thiobarbituric acid reactive substances(TBARS), and ferric reduced ability of plasma(FRAP) were determined in the colon.RESULTS: The combination therapy exhibited a significant beneficial effect in alleviation of colitis compared to controls. Overall changes in reduction of TNF-α(114.66 ± 18.26 vs 171.78 ± 9.48 pg/mg protein, P < 0.05), IL-1β(24.9 ± 1.07 vs 33.06 ± 2.16 pg/mg protein, P < 0.05), TBARS(0.2 ± 0.03 vs 0.49 ± 0.04 μg/mg protein, P < 0.01), MPO(15.32 ± 0.4 vs 27.24 ± 3.84 U/mg protein, P < 0.05), and elevation of FRAP(23.46 ± 1.2 vs 15.02 ± 2.37 μmol/L, P < 0.05) support the preference of the combination therapy in comparison to controls. Although the monotherapies were also effective in improvement of colitis markers, the combination therapy was much better in improvement of colon oxidative stress markers including FRAP, TBARS, and MPO.CONCLUSION: The present combination is a suitable mixture in control of experimental colitis and should be trialed in the clinical setting.

L-carnitine alleviates sciatic nerve crush injury in rats:functional and electron microscopy assessments

Several studies have demonstrated that L-carnitine exhibits neuroprotective effects on injured sciatic nerve of rats with diabetes mellitus. It is hypothesized that L-carnitine exhibits neuro-protective effects on injured sciatic nerve of rats. Rat sciatic nerve was crush injured by a forceps and exhibited degenerative changes. After intragastric administration of 50 and 100 mg/kg L-carnitine for 30 days, axon area, myelin sheath area, axon diameter, myelin sheath diameter, and numerical density of the myelinated axons of injured sciatic nerve were similar to normal, and the function of injured sciatic nerve also improved signiifcantly. These ifndings suggest that L-carnitine exhibits neuroprotective effects on sciatic nerve crush injury in rats.

Development and validation of a UPLC–MS/MS assay for the determination of gemcitabine and its L-carnitine ester derivative in rat plasma and its application in oral pharmacokinetics

A simple and rapid UPLC–MS/MS method to simultaneously determine gemcitabine and its L-carnitine ester derivative(2’-deoxy-2’, 2’-difluoro-N-((4-amino-4-oxobutanoyl) oxy)-4-(trimethyl amm-onio) butanoate-cytidine, JDR) in rat plasma was developed and validated.The conventional plasma sample preparation method of nucleoside analogues is solidphase extraction(SPE) which is time-consuming and cost-expensive. In this study, gradient elution with small particles size solid phase was applied to effectively separate gemcitabine and JDR, and protein precipitation pretreatment was adopted to remove plasma protein and extract the analytes with high recovery(>81%). Method validation was performed as per the FDA guidelines, and the standard curves were found to be linear in the range of 5–4000 ng/ml for JDR and 4–4000 ng/ml for gemcitabine, respectively. The lower limit of quantitation(LLOQ)of gemcitabine and JDR was 4 and 5 ng/ml, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limits. Finally, the developed method was successfully applied to investigate the pharmacokinetic studies of JDR and gemcitabine after oral administration to rats.

Enantiomeric Resolution on L-Carnitine Selective Polymers Prepared by Molecular Imprinting

L-carnitine selective polymers were prepared by molecular imprinting using methacrylic acid as the functional monomer. The acid function of the monomer is expected to form hydrogen bond and ionic interactions with the amine function of the target molecule L-carnitine. The imprinted polymers were used as stationary phases in high-performance liquid chromatography (HPLC). It was shown that L-carnitine imprinted polymer exhibited a higher affinity to its template molecule, while the non-imprinted polymer had no affinity to the compounds tested. Racemic carnitine hydrochloride was efficiently resolved on the L-carnitine imprinted polymer, and the separation factor is 1.9.

Effect of L-carnitine on Cardiomyocyte Apoptosis and Cardiac Function in Patients Undergoing Heart Valve Replacement Operation

Summary： The effects of L-carnitine, as an ingredient of cardioplegia solution, on cardiac function and cardiomyocyte apoptosis in patients undergoing heart valve replacement operation were investigated. Twenty-three cases undergoing heart valve replacement with cardiopulmonary bypass （CPB） were randomly allocated into two groups： L-carnitine group （n=12, 12 g/L L-carnitine was put in the ST. Thomas cardioplegia） and control group （n=11, identical to the L-carnitine group except that normal saline was administered instead of L-carnitine）. Serum cardial troponin I （cTnI） levels, the left ventricular ejection fraction （LVEF）, and cardiac index （CI） were measured perioperatively. A bit of myocardial tissue obtained from right atria was taken before CPB and by the end of intracardiac procedure to undergo electron microscopy examination and estimate apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL）. From the end of CPB to 3 days after operation, the serum levels of cTnI in the L-carnitine group was significantly lower than that in the control group （P〈0.05）. Heart color ultrasonogram showed that the CI index and LVEF at 7th day postoperatively in the L-carnitine group were significantly higher than in the control group （P〈0.05）. Compared to the control group, L-carnitine significantly alleviated the morphologic changes of cardiac muscle cells （electron microscopy examination） and decreased the amounts of apoptotic cardiac muscle cells （TUNEL）. Furthermore, the dosage of vasoactive drugs used after operation was significantly less in the L-carnitine group （P〈0.01）. It was concluded that L-carnitine cardioplegia solution could improve cardiac function in patients undergoing heart valve replacement operation and alleviate CPB-mediated apoptosis of cardiac muscle cells.

L-carnitine supplementation in non-alcoholic fatty liver disease: A systematic review and meta-analysis

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)dominates the landscape of modern hepatology.Affecting 25%of the general population,there is critical unmet need to identify broadly available,safe and cost-effective treatments.Cumulative evidence in animal and human models suggests that intrahepatic and skeletal muscle fatty acid oxidation is impaired in NAFLD,such that lipid accretion is not matched by efficient utilisation.L-carnitine is a crucial mediator of fatty acid metabolism in vivo,promoting mitochondrial lipidβ-oxidation and enhancing tissue metabolic flexibility.These physiological properties have generated research interest in L-carnitine as a potentially effective adjunctive therapy in NAFLD.AIM To systematically review randomised trials reporting effects of dietary L-carnitine supplementation on liver biochemistry,liver fat and insulin sensitivity in NAFLD.METHODS Search strategies,eligibility criteria and analytic methods were specified a priori(PROSPERO reference:CRD42018107063).Ovid MEDLINE,Ovid EMBASE,PubMed,Web of Science and the Cochrane Library were searched from their inception until April 2019.Outcome measures included serum concentrations of alanine and aspartate aminotransferase(ALT and AST),liver fat and insulin sensitivity assessed by the homeostasis model of insulin resistance(HOMA-IR).A random effects meta-analysis was performed for,ALT,AST and HOMA-IR measures separately.Between-study heterogeneity was measured using I2 statistics.RESULTS Five eligible randomised trials were included in the qualitative and quantitative synthesis(n=338).All of the 5 included trials assessed the effect of L-carnitine on serum ALT,identified from Italy,South Korea and Iran.Weighted mean difference(WMD)for ALT between L-carnitine and control groups after intervention was-25.34 IU/L[95%CI:-41.74-(-8.94);P=0.002].WMD for AST between L-carnitine and control groups was-13.68 IU/L(95%CI:-28.26-0.89;P=0.066).In three studies(n=204),HOMA-IR was evaluated.WMD for HOMA-IR between L-carnitine and control groups was-0.74 units[95%CI:-1.02-(-0.46);P<0.001].Two studies using validated outcome measures reported a significant reduction in liver fat in L-carnitine vs control groups post-intervention(P<0.001).CONCLUSION Pooled results indicate that L-carnitine supplementation attenuates ALT,liver fat and insulin resistance in NAFLD cohorts,confirming a beneficial effect of Lcarnitine for a highly prevalent condition with a growing economic burden.

国际最近确定的人体特定条件的必需营养物质左旋肉碱(L-Carnitine)简介

早在1905年,俄国二位科学家WL.Gulewitsch与R.Krimberg,首先从肌肉中发现提取了肉碱(Carnitine).1947年美国科学家Frankel研究确定肉碱属维生素B族,命名为 Vitamin BT。

A Pilot Clinical Trial on L-Carnitine Supplementation in Combination with Motivation Training: Effects on Weight Management in Healthy Volunteers

A 4-week low dosage (500 mg/day) L-carnitine supplementation in combination with motivation training was carried out in 24 overweight (BMI 25.8 - 26.6 kg/m2) Japanese males in the course of a double-blind randomized placebo-controlled study. L-carnitine motivated group showed significant body weight loss and a decrement of serum triglyceride level vs. the non-motivated placebo group. Serum adiponectin levels increased in both L-carnitine supplemented groups. The beneficial effects of L-carnitine were amplified by motivation training. For clinical evaluation of supplements, whose efficacy is potentially affected by inter-individual life style variability, supportive motivation training might be advisable for future clinical trials.

L-carnitine improves developmental competence of buffalo oocytes in vitro

Objective:To investigate the effect of L-carnitine on in vitro maturation and subsequent in vitro embryo production of buffalo oocytes.Methods:Cumulus oocyte complexes(COCs)were aspirated from ovaries of slaughtered buffaloes.COCs were classified into good and fair qualities based on morphological observation of numbers and integrity of cumulus cells surrounding the oocyte.Both categories of COCs were placed in in vitro maturation medium with supplementation of different concentrations(0,0.250,0.375 or 0.500 mg/mL)of L-carnitine.Oocytes from both qualities were in vitro fertilized and in vitro cultured for 7 days,to examine the developmental competence.Results:Supplementation of L-carnitine to in vitro maturation medium increased the cumulus cell expansion rate of COCs to grade A,and reduced the cumulus cell expansion of COCs to grade B and grade C in both good and fair quality oocytes.Similarly,L-carnitine induced the in vitro meiotic progression of buffalo oocytes to metaphaseⅡin both good and fair quality oocytes.Additionally,L-carnitine reduced the rate of oocyte degeneration in both good and fair quality oocytes.L-carnitine increased the rate of cleaved formation at day 2 and blastocyst formation at day 7 during in vitro culture in both qualities of oocytes.Moreover,a higher rate of blastocyst production was observed in L-carnitine-treated fair quality oocytes,which was higher than the results in the untreated good quality oocytes.Conclusions:L-carnitine enhances meiotic maturation and subsequent embryo development from both good and fair quality buffalo oocytes.

L-Carnitine Contents in the Tissues of Rabbits Fed Urea as an Alternative of Dietary Protein

The present study was aimed to observe the effects of urea ingestion, non-protein nitrogen, on the disorder of nitrogen metabolism with the L-carnitine contents using the blood, kidney, liver, and femoral muscle as markers. A total of 8 Japanese white rabbits were used in this experiment. They were fed a basal diet prepared for the control group and the nitrogen volume proportionated to one-third of CP 14%, was replaced with urea in the feed of the experimental group for 7 days. On the final day, the animals were fasted from the previous evening and sacrificed. Blood was collected into a test tube at the same time of the sacrifice and their heart, kidney, liver and femoral muscle were collected. The L-carnitine contents in each sample and the urea in the blood were determined. The results of the growth test showed that there was no significant difference. Furthermore, there was no significant difference in the contents of L-carnitine and urea in each sample. It was concluded that nitrogen replacement of the diet with urea, in the range of 1/3 of dietary protein, had neither effect on the maintenance of body weight nor nitrogen balance, including the de novo synthesis of L-carnitine.

Antioxidant Effects of L-carnitine on Rabbit

[ Objective] The paper was to study antioxidant effects of L-carnitine （LC） on rabbit, and explore its impact on SOD, GSH-PX, CAT, T-AOC and MDA activity in the plasma, brain tissue and cerebrospinal fluid of rabbit. [ Method] The healthy matured New Zealand rabbits with big ears were intragastrically administrated with LC at the dose of lmL/kg, and SOD, GSH-PX, CAT, T-AOC and MDA activities in plasma, brain tissue and cerebrospinal fluid of rabbit were determined at different periods before and after administration, respectively. [Result] After LC administration, SOD, GSH-PX CAT, and T-AOC activity in plasma, brain tissue and cerebrospinal fluid increased significantly （P 〈 0.05 ）, while MDA content decreased significantly （P 〈 0.05）. [Condusion ] LC oral solution shows antioxidant effects on rabbit.

Effects of L-carnitine on Blood Lipid Metabolism and Antioxidation in Hyperlipidemia Rats

[Objective] To study the effects of L-carnitine （LC） on lowering the high blood lipid and antioxidation in hyperlipidemia rats. [Method] 50 healthy SD rats were randomly divided into 5 groups. They were fed with standard diet, high-cholesterol diet and high-cholesterol diet with 0.25, 0.5, 1.0 g/（ kg · d） LC. After the LC groups were consecutively orally administered LC for 28 days, rat serum total cholesterol （ TC）, triglyceride （TG）, high density lipoprotein （ HDL-C）, low density lipoprotein （LDL-C） content, as well as super oxide dismutase （SOD） activity and malondial- dehyde （MDA） content in serum and liver were determined. [ Reset~ Compared with the high-fat model group, LC could significantly reduce the se- rum TC, TG, LDL-C levels, increase HDL-C level, and enhance SOD activity in serum and liver, decrease the content of MDA （ P 〈0.05）. [ Con- Clusion] LC might have a significant role in lowering the high blood lipid and improving internal antioxidant capacity in hyperlipidemia rats.

Effects of L-Carnitine on Propofol-Induced Inhibition of Free Fatty Acid Metabolism in Fasted Rats and in Vitro

Background: Propofol inhibits fatty acid oxidation and induces mitochondrial deficiency, a possible mechanism involved in propofol infusion syndrome. This study investigated how propofol influences fatty acid, glucose, and amino acid metabolism, as well as whether L-carnitine may improve suppression of free fatty acid metabolism. Methods: Male Sprague-Dawley rats, fasted for 16 hours, were allocated to the following two groups: (Group P;continuous intravenous administration of 10 mg/kg/h propofol;n = 8) and (Group P + C;intravenous administration of 50 mg/kg and then 50 mg/kg/h L-carnitine continuously;n = 8). Concentrations of glucose, free fatty acid (FFA), amino acids, in-sulin, and β-hydroxybutyric acid were measured at the start and then one, two, and three hours after propofol administration. Intrahepatic triglyceride levels were measured at the end of experiments. In vitro experiments comprised measurement of oxygen consumption in human hepatocytes (Hepg2) and investigating dependency on palmitic acid, glucose, and glutamine as fuel during propofol administration, with or without L-carnitine. Results: FFA increased in Group P and gradually decreased in Group P + C. There were significant differences between the two groups (Group P;331.2 ± 64.5 μM vs. Group P + C;199 ± 73.6 μM). Glucose decreased in both groups (Group P;53.8 ±16.6 mg/dL vs. Group P + C;88 ± 11.3 mg/dL). Amino acid concentrations were higher in Group P + C after experiments;alanine and glutamine increased significantly. β-hydroxybutyric acid increased significantly in Group P + C, and intrahepatic triglyceride decreased in Group P + C. Dependency on fatty acid metabolism significantly decreased with propofol only;addition of L-carnitine prevented these effects. Conclusions: Propofol impaired mitochondrial fatty acid metabolism, which was compensated mainly by a switch to glucose metabolism and partially by amino acid metabolism. Addition of L-carnitine may improve this imbalance of energy metabolism.

Relationship between Serum L-Carnitine Levels and Sperm Parameters in Boars

This study evaluated the relationship between serum L-carnitine level and sperm parameters in young boars. Serum L-carnitine and semen characteristics were determined for 61 young Duroc boars between the ages of 590 and 630 days. Multiple linear regression analysis was performed to predict total and progressive motility and the total number of spermatozoa based on serum total L-carnitine and free L-carnitine levels. Total number of spermatozoa was not associated with basal serum L-carnitine levels. A regression equation was found in which both total L-carnitine levels and free L-carnitine levels were significant predictors of total and progressive motility (P 0.05). These results suggest that serum L-carnitine level is an important selection parameter for stock boars.

Effects of L-carnitine and Branched-Chain Amino Acids on Energy Metabolism,Body Composition,and Delayed-Onset Muscle Soreness after Exercise in Healthy Subjects

Background Specific nutrients combined with exercise may prevent a loss of lean body mass and consequently prevent sarcopenia.We examined the effects of 2 weeks of supplementation with L-carnitine and a single dose of branched-chain amino acids(BCAAs)on energy metabolism and body composition before and after exercise and on post-exercise muscle soreness in healthy subjects.Methods A total of 12 young,untrained,healthy women were randomly assigned to two groups who received either 2 weeks of supplementation with L-carnitine(1000 mg/day)and a single dose of BCAAs plus 200 kcal energy(LCAR+BCAA group,n=6)or 200 kcal energy alone(control group,n=6)before 60 min of exercise.Energy substrate metabolism and body composition by bio-impedance were examined before and after exercise.Delayed-onset muscle soreness(DOMS)was evaluated by using a visual analogue scale for 3 days after exercise.Results Serum concentrations of free and acyl-L-carnitine in the LCAR+BCAA group were not significantly different from those in the control group.There were no significant differences in body composition before or after exercise between the two groups.Although serum free fatty acid levels 120 min after the oral ingestion of BCAAs were significantly lower in the LCAR+BCAA group than in the control group,there were no significant differences in serum free fatty acid levels immediately after and 60 min after exercise.DOMS for 3 days after exercise was lower in the LCAR+BCAA group than in the control group,but this difference was not significant.Conclusion Continuous supplementation with L-carnitine combined with a dose of BCAAs in young,untrained,healthy subjects caused a blunted response of stimulated lipolysis after exercise.

Effects of L-carnitine on treatment outcomes of COVID-19 patients hospitalized in intensive care units:A double-blind randomized clinical trial

Objective:To assess the effects of L-carnitine on the outcomes of patients with moderate to severe coronavirus disease 2019(COVID-19)in intensive care unit(ICU).Methods:This double-blind clinical trial was carried out in 2022-2023.64 Patients with COVID-19 were selected from Amiralmomenin and Khansari hospitals in Arak,Iran.They were randomly assigned to the control and the L-carnitine treatment group via block randomization.Venous blood gases,disease severity,and levels of D-dimer,lactate dehydrogenase,ferritin,and C-reactive protein were daily assessed during the seven days of the intervention,and the length of ICU stay,the need for endotracheal intubation,and mortality rate were documented.Results:There were significant differences in length of ICU stay,the need for endotracheal intubation,and levels of D-dimer,lactate dehydrogenase,ferritin,APACHE栻score,and C-reactive protein between the two groups(P<0.05).However,the groups did not significantly differ in mortality rate and venous blood gas indexes(P>0.05).Conclusions:L-carnitine can improve outcomes of patients with COVID-19.Therefore,it can be used as an adjuvant therapy for these patients.