L-carnitine Group Research Articles

The Effects of L-Carnitine Therapy on Respiratory Function Tests in Chronic Hemodialysis Patients

Background. Respiratory functions are affected during hemodialysis. The strength of respiratory muscles, ultrafiltration rate, and acid-base balance have been suggested as important factors. L-carnitine is crucial for energy producing, utilization of fatty acid, and possible amino acids. A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and especially by its loss during dialysis. This study was performed to investigate the chronic effects of L-carnitine treatment on respiratory functions in adults receiving chronic hemodialysis therapy. Methods. A total of 20 hemodialysis patients were scheduled to take L-carnitine supplementation (20 mg/kg three times/week) (group 1), and the rest of 20 hemodialysis patients served as the control group and were observed without supplementation with L-carnitine (group 2). Pre- and post-dialytic L-carnitine levels and post-dialytic respiratory functions tests were performed in both groups at baseline and after six months. Results. The average concentration of free and total carnitine levels increased significantly after six months of supplementation (p < 0.01). While a statistically significant increase between postdialytic forced expiratory volume in one second/forced vital capacity values after treatment period (77.10 ± 12.15 and 83.00 ± 14.49, before and after treatment, respectively, p < 0.05) was observed, the increase of vital capacity, forced expiratory volume in one second, and forced expiratory flow between 25–75% of expired vital capacity were not significant in the treatment group (p > 0.05). Conclusion. Intravenous L-carnitine supplementation could contribute to the management of respiratory dysfunction in chronic hemodialysis patients by improving FEV1/FVC. The mechanism by which LC causes these effects merits further investigation.

Effects of Dietary L-carnitine Supplementation on Growth, Muscle Fatty acid Composition and Economic Profit of Rainbow Trout (Oncorhynchus mykiss)

In this study, the effect of dietary L-carnitine on growth, proximate and muscle fatty acid compositions of rainbow trout (Oncorhynchus mykiss) were investigated. The fish were fed with diets containing 300 mg kg -1 L-carnitine (LC300), other group was fed with diets containing 600 mg kg -1 L-carnitine (LC600) and control group was not supplementary L-carnitine for 63 days. The weight gain of LC600 fed with L-carnitine supplemented was found to be 7.73% higher than in control group. Feed conversion ratio in LC600 (1.66) and LC300 (1.60) is better than in control group (2.00). L-carnitine supplemented groups would be lower cost of production than control. Economic conversion ratio (ECR) of LC300 (2.71 US.$ kg -1 ) would represent a saving of 0.44 US.$ kg -1 compared to the control. L-carnitine administration did not affect proximate composition of muscle except for protein percent. Protein content of L-carnitine supplemented groups was higher than control group. Total saturated monounsaturated and polyunsaturated muscle fatty acid content increased by L-carnitine supplementation in rainbow trout. The results indicate that supplementation of 600 mg L-carnitine/kg diet is more effective on growth than the other L-carnitine supplementation level 300 mg kg -1 and control diet in commercial cage conditions.

L-carnitine pre-treatment reduces apoptotic cell death in seven-day-old rats hypoxia ischemia

The pre and post-treatment effects of L-carnitine on apoptotic cell death due to hypoxia-ischemia in various regions of the brains of seven-day-old rats were investigated. L-carnitine (group 1; n=8) or saline (group 2; n=8) was administered intraperitoneally to seven-day-old rats before hypoxia-ischemia. In addition, 16 seven-day-old rats were given L-carnitine (group 3; n=8) or saline (group 4; n=8) after hypoxic ischemic insult. Apoptotic cell death was investigated by terminal dUDP-biotin nick end-labeling (TUNEL) in all subjects following three days of recovery. In the evaluation of TUNEL-positive cells, firstly the areas (in square millimeters) of the hippocampus, striatum and cortex in the right and left hemispheres were measured by IMAGE analysis. Then the numerical density was calculated as the number of cells per square millimeter by counting all TUNEL-positive cells. Afterwards, the ratios of right side numerical density to the sum of right and left sides' numerical densities (right apoptosis index) were calculated for every brain region in rats receiving L-carnitine and they were compared with the vehicle groups. The right apoptosis indexes of the hippocampus (37.4 ± 18.8; mean ± SD) and striatum (39.2 ± 15.2) in rat pups pre-treated with L-carnitine were significantly lower than those in the vehicles (59.8 ± 17.9 vs. 60.4 ± 19.6 respectively) (p< 0.05), whereas they were not changed by L-carnitine pre-treatment in the cortex. Additionally, L-carnitine post-treatment had no effect on right apoptosis indexes in any of the three brain regions. It is concluded that pre-treatment with L-carnitine might play a role in reducing apoptotic cell death due to neonatal hypoxic ischemic brain injury. Our results suggested that L-carnitine was useful in perinatal asphyxia for preventing hypoxic ischemic brain injury.

Is there a Role for Oral L-Carnitine Therapy in Anemia and Cardiac Dysfunction Management in Egyptian Patients on Maintenance Hemodialysis?

Aim: L-carnitine is a short organic hydrosoluble molecule and is present in biological materials like free carnitine and acylcarnitines, which constitute the carnitine system. Long-term intermittent hemodialysis is associated with a reduction in plasma and tissue L-carnitine levels. Available studies on carnitine supplementation suggest the use of this molecule in dialysis, especially for those patients with cardiac complications, impaired exercise and functional capacities, and increased episodes of hypotension. Moreover, in some patients, the improved stability of erythrocyte membranes with L-carnitine supplementation may decrease erythropoietin requirements, thus leading to a reduction of dialytic costs. To study if there a possible advantageous effects for L– carnitine oral supplementation in anemia and cardiac dysfunction management in a cohort of Egyptian patients on maintenance hemodialysis. Methods: Fifty-five patients with chronic renal failure on maintenance hemodialysis were classified into 2 groups: L-carnitine group: 20 patients (12 male and 8 female, mean age 47.66±17.73 years, hemodialysis duration 51.36±18.14 months, subjected to three sessions/week reaching a Kt/V of 1.49±0.37) they received oral L-carnitine therapy 1.500 mg/day and control group: 35 patients (24 male and 11 female, mean age 37.9±14.7 years, hemodialysis duration 53.83±15.17 months, subjected to three sessions/week reaching Kt/V of 1.33±0.23). Both groups were on Erythropoietin therapy and IV iron whenever indicated. Echogardiographic studies were performed before and at the end of the study. Results: Serum hemoglobin were comparable in the L-carnitine group and control group at the start and six months after therapy (8.63±1.77 and 9.39±2.02 gm/dl, p= 0.18, 10.49±1.65 and 10.92±2.48 gm/dL p= 0.76 respectively). The weekly maintenance dose of Erythropoietin in spite of being lower in L-carnitine group (80.16±35.61 units/kg) compared to control group (91.9±38.21 units/kg) it does not reach a statistical significance (p= 0.20). No significant improvement could be observed in echogardiographic findings in the L-carnitine group after therapy. Conclusion: The role of L-carnitine in hemodialysis patients is questionable. Our study revealed no observed significant improvement in echocardiographic findings 6 months after therapy. However, -a statistically non significant-reduction in Erythropoietin dose was achieved in the L-carnitine-treated compared to the control group while maintaining comparable target hemoglobin in both groups. Long-term studies including larger number of patients are required to clarify its role in hemodialysis patients.

Does L-carnitine increase serum TNF -α and IGF-1 during liver regeneration in the rat?

Aim: We sought to evaluate the effect of L-carnitine administration on the levels of IGF-1, TNF-\alpha, and lipid peroxidation during hepatic regeneration for up to 72 h in an experimental partial hepatic resection rat model. Materials and methods: Sixty rats were divided into 3 groups: control and low-dose (100 mg/kg) and high-dose (200 mg/kg) L-carnitine. Each group was divided into 2 sub groups (24 and 72 h after partial hepatectomy). Partial (70%) hepatectomy was performed after 7 days of intra-peritoneal administration of L-carnitine. After partial hepatectomy, L-carnitine was also administered to rats until sacrifice. Serum IGF-1, TNF-\alpha, and tissue malondialdehyde levels were determined in all groups before and at 24 and 72 h after surgery. Results: Serum TNF-\alpha increased significantly in the control group during the regeneration period. The low dose of L-carnitine (100 mg/kg) decreased the elevation of TNF-\alpha whereas the high dose (200 mg/kg) increased it. In the control group, the IGF-1 level decreased in the first 24 h after surgery and then increased. The IGF-1 level behaved similarly in the L-carnitine groups. The malondialdehyde level in the control group increased during the first 24 h and then decreased. Similarly in the L carnitine groups, the malondialdehyde level increased during the first 24 h and then decreased significantly in a dose-dependent manner. Conclusion: Three types of biochemical pathways are essential in liver regeneration: cytokine, growth factor, and metabolic pathways. We conclude that, in addition to its effects on energy metabolism, high-dose L-carnitine may promote liver regeneration by increasing IGF-1, TNF-\alpha, and decreasing malondialdehyde.

Effects of L-carnitine and iron diet supplementations on growth performance, carcass characteristics and blood metabolites in fattening pigs

The aim of this study was to evaluate the effect of dietary L-carnitine supplementation either with or without extra Fe supplementation from Fe-amino acid (Fe-AA) complex on body weight gain, feed conversion, carcass characteristics and blood metabolite concentrations in fattening pigs. The study was carried out with 75 fatteners (30.100 kg body weight), divided into three groups, of 25 pigs each. The control group was given a basal diet that contained 85 mg/kg of Fe from premix. A L-carnitine group was given a basal diet supplemented with 100 mg/kg of L-carnitine, and a L-carnitine+Fe group was given a basal diet supplemented with 100 mg/kg of L-carnitine and 60 mg/kg of Fe from a Fe-AA complex. The supplement of L-carnitine to the diets did not have any effects on the growth performance and carcass traits. The L-carnitine supplement decreased the concentration of triglycerides (p.0.05), cholesterol (p .0.05) and low-density lipoproteins (p .0.01) in the blood serum of pigs, while it increased (p.0.01) the concentration of high-density lipoproteins. The combination of L-carnitine+Fe increased the growth performance of growing pigs (p .0.05) and the lean percentage and fatless ham weight in carcass and also increased (p .0.05) the Fe content in the blood serum and the longissimus dorsi muscle of pigs. The results suggest the more effective outcomes can be reached when L-carnitine+Fe rather than only L-carnitine is used in diets.;

Role of l-carnitine in the prevention of seminiferous tubules damage induced by gamma radiation: a light and electron microscopic study

The present study, we hypothesized that L-carnitine can minimize germ-cell depletion and morphological features of late cell damage in the rat testis following gamma (gamma)-irradiation. Wistar albino male rats were divided into three groups. Control group received physiological saline 0.2 ml intraperitoneally (i.p.), as placebo. Radiation group received scrotal gamma-irradiation of 10 Gy as a single dose plus physiological saline. Radiation + L-carnitine group received scrotal gamma-irradiation plus 200 mg/kg i.p. L-carnitine. L-carnitine starting 1 day before irradiation and 21 days (three times per week) after irradiation. Testis samples of the all groups were taken at day 21, 44 and 70 post-irradiation. All samples were processed at the light and electron microscopic levels. Morphologically, examination of gamma-irradiated testis revealed presence of marked disorganization and depletion of germ cells, arrest of spermatogenesis, formation of multinucleated giant cells, and vacuolization in the germinal epithelium. The type and extent of these changes varied at different post-treatment intervals. The damage was evident at the 21st day and reached maximum level by the 44th day. By day 44 post-irradiation, the changes were most advanced, and were associated with atrophied seminiferous tubules without germ cells, the increase in the number and size of vacuolizations in germinal epithelium, and the absent multinucleated giant cells due to spermatids had completely disappeared. The increase in nucleus invaginations, the dilatation of smooth endoplasmic reticulum cysternas and the increase in the number and size of lipid droplets in the Sertoli cells were determined at the electron microscopic level. In conclusion, L-carnitine supplementation during the radiotherapy would be effective in protecting against radiation-induced damages in rat testis, and thereby may improve the quality of patient's life after the therapy.

L-carnitine improves embryo quality and increases blastocyst development rate in couples undergoing ICSI

OBJECTIVE: Stabilization of the mitochondrial membrane leads to increase in the supply of energy to the organelle and protect the cell from apoptotic death. L-Carnitine (LC) is a potent antioxidant that increases the supply of energy to the organelles, stabilizes the mitochondrial membranes, and protects cells against DNA damage. The objective of our study was to examine if supplementing the culture media with LC improves embryo quality and the %BDR in couples undergoing ICSI.DESIGN: Prospective clinical study.MATERIALS AND METHODS: We included those patients who had more than 15 fertilized oocytes and were not interested in embryo cryopreservation at day 3. A total of 617 oocytes obtained from 38 infertile couples (12 with male factor infertility, 11 female factor infertility and 15 combined male and female factor infertility) were fertilized by ICSI. Embryos (2PN) were classified into two groups:, Group A (n = 131): embryos were incubated in ISM1 cleavage culture medium (Medicult, Denmark) supplemented with 0.3mg/ mL LC and Group B (n = 147): embryos incubated in ISM1 cleavage culture medium without LC. On day 3, embryos in both groups were transferred to ISM2 extended culture medium (Medicult Denmark) with LC (group A) or without LC (group B). Only grade 1 embryos were allowed for incubation to day 5 and blastocyst development rate (%BDR) was assessed.RESULTS: LC at 0.3mg/mL concentration significantly improves the quality of embryos at day 3 and the %BDR at day 5 compared with the untreated group (P<0.001 and P<0.001 respectively) (Table 1).Table 1Comparison of % grade 1 embryos at day 3 and %BDR at day 5 between Groups A and Group BParameterGroup A (%)Group B (%)∗P value <0.05 was considered significant by Wilcoxon test. Values are median (25th and 75th percentile). P value% Grade I embryos (day 3)100.0 (100.0, 100.0)60.0 (50.0, 71.4)<0.001% BDR (day 5)75.0 (60.0, 100.0)50.0 (33.3, 66.7)<0.001∗ P value <0.05 was considered significant by Wilcoxon test. Values are median (25th and 75th percentile). Open table in a new tab OBJECTIVE: Stabilization of the mitochondrial membrane leads to increase in the supply of energy to the organelle and protect the cell from apoptotic death. L-Carnitine (LC) is a potent antioxidant that increases the supply of energy to the organelles, stabilizes the mitochondrial membranes, and protects cells against DNA damage. The objective of our study was to examine if supplementing the culture media with LC improves embryo quality and the %BDR in couples undergoing ICSI. DESIGN: Prospective clinical study. MATERIALS AND METHODS: We included those patients who had more than 15 fertilized oocytes and were not interested in embryo cryopreservation at day 3. A total of 617 oocytes obtained from 38 infertile couples (12 with male factor infertility, 11 female factor infertility and 15 combined male and female factor infertility) were fertilized by ICSI. Embryos (2PN) were classified into two groups:, Group A (n = 131): embryos were incubated in ISM1 cleavage culture medium (Medicult, Denmark) supplemented with 0.3mg/ mL LC and Group B (n = 147): embryos incubated in ISM1 cleavage culture medium without LC. On day 3, embryos in both groups were transferred to ISM2 extended culture medium (Medicult Denmark) with LC (group A) or without LC (group B). Only grade 1 embryos were allowed for incubation to day 5 and blastocyst development rate (%BDR) was assessed. RESULTS: LC at 0.3mg/mL concentration significantly improves the quality of embryos at day 3 and the %BDR at day 5 compared with the untreated group (P<0.001 and P<0.001 respectively) (Table 1).

Effect of Oral L-Carnitine Administration on Insulin Sensitivity and Lipid Profile in Type 2 Diabetes Mellitus Patients

Aim: It was the aim of this study to evaluate the effect of oral L-carnitine administration on insulin sensitivity and lipid profile in subjects with type 2 diabetes mellitus. Subjects and Methods: A randomized, double-blind, placebo-controlled clinical trial was carried out in 12 subjects with type 2 diabetes. Six subjects received L-carnitine 1 g orally 3 times a day before meals for a period of 4 weeks. Six other individuals took a placebo for the same period of time, as the control group. Before and after the intervention, insulin sensitivity and the lipid profile were estimated. To assess insulin sensitivity, the euglycemic-hyperinsulinemic clamp technique was performed. Wilcoxon’s signed rank and the Mann-Whitney U test were used for the statistical analyses. Results: There were no significant differences in basal clinical characteristics between the 2 groups. Insulin sensitivity and the basal lipid profile were similar. There were no significant changes in either group after the intervention in insulin sensitivity (3.2 ± 1.2 vs. 4.5 ± 1.7 mg/kg/min, p = 0.115, and 3.5 ± 0.6 vs. 3.5 ± 0.4 mg/kg/min, p = 0.917, for the placebo and L-carnitine groups, respectively) and in lipid profile. Conclusion:L-Carnitine orally administered for a period of 4 weeks did not modify insulin sensitivity or the lipid profile.

Estudio exploratorio de la capacidad aerobia en pacientes en hemodiálisis: efecto de la suplementación con L-carnitina

Chronic hemodialyzed patients have a low level of aerobic capacity, caused by the pathologies concomitant to renal insufficiency, according with a low level of physical activity. One of the factors that would contribute to this level of aerobic capacity is the L-carnitine deficit on skeletal muscle. However, the value of the supplementation of L-carnitine to improve the physical fitness has been controversial. The objective of this work was to evaluate the effect of the administration of L-carnitine on VO2 max in hemodialyzed patients. A group of 21 patients (20-50 years old) on a program of chronic hemodialysis was studied. During 12 weeks, 13 of them received L-carnitine, 7 men and 6 women, 38.8 (9.5) years old; BMI 24.2 (2.1) Kg/m2; 8 of them received placebo, 4 men and 4 women, 35.8 (11.4) years old; BMI 24.5 (5.8) Kg/m2. There was an increase in VO2 peak on L-carnitine group from 16.3 (2.8) mL x Kg(-1) x min(-1) to 19.5 (3.3) mL x Kg(-1) x min(-1), and the same was seen in the placebo group (increase in VO2 peak from 14.8 (3.8) mL x Kg(-1) x min(-1) to 18.9 (4.8) mL x Kg(-1) x min(-1)). The L-carnitine and placebo groups did not show statistical differences at the end of this study (all values above p > 0.05). In this group of patients, the intravenous supplementation of L-carnitine during 12 weeks did not have an impact on the improvement of the VO2 peak.

Comparison of the Effects of Sodium Nitroprusside and L-Carnitine in Experimental Ischemia-Reperfusion Injury in Rats

Aim The aim of this study was to evaluate the protective effect of sodium nitroprusside (SNP) as a nitric oxide (NO) donor and L-carnitine intraperitoneal administration to treat experimental ischemia-reperfusion (I/R) in rats. Materials and methods Rats were divided into four groups, each one consisting of 10 animals. Group 1 was subjected to a sham operation. In group 2, an I/R process was applied to the rats. In group 3, SNP (5 mg/kg) and in group 4, L-carnitine (500 mg/kg) was administered in addition to the I/R process. Ileal tissue samples were obtained for analysis of tissue malonyl dialdehyde (MDA) and for histopathologic examination. Results By histopathologic examination, the I/R group showed a significant difference from the SNP and L-carnitine groups ( P < .05). There was no difference between the sham, the SNP, and the L-carnitine groups ( P > .05). SNP used as an NO donor produced a significant decrease in MDA levels. There was a significant difference between the MDA levels of the SNP and the I/R groups ( P < .05). Also, the difference between this group and the I/R group was significant ( P < .05). Conclusion SNP helped to both prevent and reduce mucosal damage in terms of histological and tissue MDA levels. Since the results of the L-carnitine group and the SNP group were similar, L-carnitine was as effective as exogenous NO.

L-carnitine as an antiapoptotic supplement in mouse embryo culture media

ObjectiveHuman embryos generated from in vitro fertilization (IVF) show varying degrees of cytoplasmic fragmentation. Reports suggest that cytoplasmic fragmentation in human embryos arises from apoptosis. Mitochondrial membrane potential and energy production in preimplantation embryos have recently been the focus of many studies. L-Carnitine (LC) has no major side effects on embryonic cells, interactions with other drugs or teratogenicity. It acts by stabilizing the mitochondrial membrane and protecting the cell from apoptosis. The aim of our study was to investigate the antiapoptotic effect of LC supplementation in mouse embryo culture media.DesignProspective in vitro study.Materials and methodsA total of 240 mouse embryos (8-cell) were randomly assigned into 4 groups: group 1: control (HTF media only); groups 2 (Actinomycin D 5 ng/mL; dose based on previous literature) group 3–4: (Actinomycin D 5 ng/mL + two concentrations of LC (0.3 and 0.6 mg/mL). LC concentrations were based on pilot study by our group to optimize the dose of LC in mouse embryo culture media. Embryos were incubated at 37°C in 5% CO2. Assessment of embryos development was done after 48 hours by examining the percentage blastocyst development rate (%BDR). After TUNEL staining, the blastocysts were examined by confocal microscopy. Apoptosis was measured by examining the percentage of TUNEL positive blastomeres.ResultsTableaP<0.05 considered significant using Fisher's exact test for %BDR differences; bP<0.05 was significant for differences in apoptosis using Kruskal-Wallis or Wilcoxon test. cP differences between Actinomycin group and Actinomycin + LC groups. Open table in a new tab ConclusionsL-Carnitine improves the blastocyst development rate and reduces apoptosis. Supplementing in vitro culture media with L-Carnitine may improve the fertilization outcome. ObjectiveHuman embryos generated from in vitro fertilization (IVF) show varying degrees of cytoplasmic fragmentation. Reports suggest that cytoplasmic fragmentation in human embryos arises from apoptosis. Mitochondrial membrane potential and energy production in preimplantation embryos have recently been the focus of many studies. L-Carnitine (LC) has no major side effects on embryonic cells, interactions with other drugs or teratogenicity. It acts by stabilizing the mitochondrial membrane and protecting the cell from apoptosis. The aim of our study was to investigate the antiapoptotic effect of LC supplementation in mouse embryo culture media. Human embryos generated from in vitro fertilization (IVF) show varying degrees of cytoplasmic fragmentation. Reports suggest that cytoplasmic fragmentation in human embryos arises from apoptosis. Mitochondrial membrane potential and energy production in preimplantation embryos have recently been the focus of many studies. L-Carnitine (LC) has no major side effects on embryonic cells, interactions with other drugs or teratogenicity. It acts by stabilizing the mitochondrial membrane and protecting the cell from apoptosis. The aim of our study was to investigate the antiapoptotic effect of LC supplementation in mouse embryo culture media. DesignProspective in vitro study. Prospective in vitro study. Materials and methodsA total of 240 mouse embryos (8-cell) were randomly assigned into 4 groups: group 1: control (HTF media only); groups 2 (Actinomycin D 5 ng/mL; dose based on previous literature) group 3–4: (Actinomycin D 5 ng/mL + two concentrations of LC (0.3 and 0.6 mg/mL). LC concentrations were based on pilot study by our group to optimize the dose of LC in mouse embryo culture media. Embryos were incubated at 37°C in 5% CO2. Assessment of embryos development was done after 48 hours by examining the percentage blastocyst development rate (%BDR). After TUNEL staining, the blastocysts were examined by confocal microscopy. Apoptosis was measured by examining the percentage of TUNEL positive blastomeres. A total of 240 mouse embryos (8-cell) were randomly assigned into 4 groups: group 1: control (HTF media only); groups 2 (Actinomycin D 5 ng/mL; dose based on previous literature) group 3–4: (Actinomycin D 5 ng/mL + two concentrations of LC (0.3 and 0.6 mg/mL). LC concentrations were based on pilot study by our group to optimize the dose of LC in mouse embryo culture media. Embryos were incubated at 37°C in 5% CO2. Assessment of embryos development was done after 48 hours by examining the percentage blastocyst development rate (%BDR). After TUNEL staining, the blastocysts were examined by confocal microscopy. Apoptosis was measured by examining the percentage of TUNEL positive blastomeres. ResultsTableaP<0.05 considered significant using Fisher's exact test for %BDR differences; bP<0.05 was significant for differences in apoptosis using Kruskal-Wallis or Wilcoxon test. cP differences between Actinomycin group and Actinomycin + LC groups. Open table in a new tab aP<0.05 considered significant using Fisher's exact test for %BDR differences; bP<0.05 was significant for differences in apoptosis using Kruskal-Wallis or Wilcoxon test. cP differences between Actinomycin group and Actinomycin + LC groups. ConclusionsL-Carnitine improves the blastocyst development rate and reduces apoptosis. Supplementing in vitro culture media with L-Carnitine may improve the fertilization outcome. L-Carnitine improves the blastocyst development rate and reduces apoptosis. Supplementing in vitro culture media with L-Carnitine may improve the fertilization outcome.

Effect of L-Carnitine on Oxidative Damage to Liver, Kidney and Spleen Induced by Phenylhydrazine in Mice

Ozcan, A., Atakisi, E., Karapehlivan, M., Atakisi, O. and Citil, M. 2007. Effect of L-carnitine on oxidative damage to liver, kidney and spleen induced by phenylhydrazine in mice. J. Appl. Anim. Res., 32: 97–100. To investigate the ameliorative effect ofL- carnitine on phenylhydrazine induced oxidative damage to liver, kidney and spleen, twenty-eight Swiss albino mice were divided into four groups and injected 0.9% NaCl (control), 40 mg/kg/day phenylhydrazine, phenylhydrazine+L-carnitine or 1000 mg/kg/day L-carnitine. Malondialdehyde (MDA) level was found to be significantly (P<0.001) lower in phenylhydrazine+L-carnitine group compared to the phenylhydrazine group in all tissues. Reduced kidney glutathione (GSH) level in phenylhydrazine given group was restored to normal by L-carnitine. However, increased uric acid level by phenylhydrazine was not decreased by L-carnitine administration. It appears that L-carnitine may prevent tissue damage and lipid peroxidation induced by phenylhydrazine.

L-Carnitine in the treatment of fatigue in adult celiac disease patients: A pilot study

Background Fatigue is common in celiac disease. L-Carnitine blood levels are low in untreated celiac disease. L-Carnitine therapy was shown to improve muscular fatigue in several diseases. Aim To evaluate the effect of L-carnitine treatment in fatigue in adult celiac patients. Methods Randomised double-blind versus placebo parallel study. Thirty celiac disease patients received 2 g daily, 180 days (L-carnitine group) and 30 were assigned to the placebo group (P group). The patients underwent clinical investigation and questionnaires (Scott-Huskisson Visual Analogue Scale for Asthenia, Verbal Scale for Asthenia, Zung Depression Scale, SF-36 Health Status Survey, EuroQoL). OCTN2 levels, the specific carnitine transporter, were detected in intestinal tissue. Results Fatigue measured by Scott-Huskisson Visual Analogue Scale for Asthenia was significantly reduced in the L-carnitine group compared with the placebo group ( p = 0.0021). OCTN2 was decreased in celiac patients when compared to normal subjects (−134.67% in jejunum), and increased after diet in both celiac disease treatments. The other scales used did not show any significant difference between the two celiac disease treatment groups. Conclusion L-Carnitine therapy is safe and effective in ameliorating fatigue in celiac disease. Since L-carnitine is involved in muscle energy production its decreased absorption due to OCTN2 reduction might explain muscular symptoms in celiac disease patients. The diet-induced OCTN2 increase, improving carnitine absorption, might explain the L-carnitine treatment efficacy.

L-carnitine inhibits a subset of platelet activation responses in chronic uraemia

Activated uraemic platelets expose the aminophospholipid phosphatidylserine (PS) at their outer surface, which generates a cell procoagulant phenotype and seems at least partly due to an increase in cell caspase-3 activity. L-carnitine (LC) may decrease surface-exposed PS in stored apheresis platelets and inhibit the activity of recombinant caspases, but its effects on platelet activation response with PS externalization have not been ascertained in chronic renal failure. In the present study, we investigated in vitro and in vivo the effects of LC on PS exposure in platelets from chronic uraemic patients. Platelet PS-exposure was assayed by flow cytometry using annexin V. Caspase activity in platelets was determined by the cleaving activity of the specific substrate DEVD-pNA and by a flow cytometric assay using rhodamine-fluorescence. The effects of LC in vivo were examined in a prospective cross-over trial including 10 patients on maintenance haemodialysis (HD) who were randomly allocated to two different treatment groups: LC (2 g i.v.) for 4 months followed by placebo (2 g i.v.) for another 4 months (group A), or placebo followed by LC (group B). PS-exposing platelets in blood samples obtained from HD patients were significantly higher than in healthy subjects (P<0.001) under both unstimulated and agonist-stimulated conditions. When uraemic platelets were pre-incubated with LC before agonist stimulation, platelet PS exposure proved to be significantly reduced (-13.7% for 0.5 mM LC and -25% for 5 mM LC). Pre-incubation of uraemic platelets with LC again significantly decreased the cells' caspase activity (P<0.05). In HD patients (Group A), LC supplementation was associated with a significant decrease (P<0.05) in platelet PS exposure followed by a progressive increase during treatment with placebo. In the other group of patients, while no change in platelet PS exposure was observed during the first 4 months of treatment with placebo, a significant reduction (P<0.05) in PS-positive platelets occurred after 2 and 4 months of LC therapy. Our data show that LC may reduce, possibly via inhibition of caspase activity, the exposure of PS in activated uraemic platelets. These findings may have implications for the thrombophilic tendency of uraemia.

Does l‐carnitine have any effect on cold preservation injury of non‐fatty liver in the University of Wisconsin solution?

To evaluate the protective effect of l-carnitine on liver tissue preserved in University of Wisconsin (UW) solution. Twenty Wistar Albino rats were divided into two groups, a control (UW) group and a UW plus l-carnitine group. Retrieved liver grafts were preserved in UW and UW plus l-carnitine solutions at +4 degrees C. Preservation solution samples were assessed at 2, 24, 36, and 48 h to measure alanine aminotransferase and acid phosphatase activity. Tissue injury was scored on paraffin sections. No micro or macrovacuolar fat droplets were observed in the tissue slices. l-Carnitine effectively decreased enzyme release when added to UW solution (P < 0.05). In addition to fatty liver, l-carnitine might be a metabolic adjunct in preservation solutions for non-fatty liver within UW solution.

Dietary l-carnitine supplementation enhances the lipopolysaccharide-induced acute phase protein response in broiler chickens

The objective of the present study was to evaluate the potential effects of dietary l-carnitine supplementation on acute phase protein response upon a lipopolysaccharide (LPS) challenge of male broiler chickens receiving a commercial broiler diet supplemented with 15 or 100 mg l-carnitine/kg or an unsupplemented (control) diet from 14 days of age onwards. At 28 days of age, eight chickens per dietary treatment were weighed and subcutaneously injected with 300 μg LPS from E. coli (100 μg LPS/ml saline) or 3 ml saline (unsupplemented group only). During the next 10 days, blood samples were taken repeatedly and analysed for their hemopexin (HX) and alpha-1 acid glycoprotein (AGP) levels. Extra dietary l-carnitine did not affect broiler performance. At day 1 postinjection, plasma HX and AGP levels were significantly increased in all treatment groups. However, the elevations in circulating HX and AGP levels were more pronounced in the l-carnitine supplemented chickens, especially in the 100 mg l-carnitine group. It is concluded that extra l-carnitine in the diet of broiler chickens enhances or advances the acute phase protein response. The exact mode of action needs to be elucidated but seems to be consistent with a glucocorticoid mimicking effect.

The effects of exogenous l-carnitine on lipid peroxidation and tissue damage in an experimental warm hepatic ischemia-reperfusion injury model

Background: l-Carnitine is the essential endogenous factor for the transport of long-chain fatty acids from the cytoplasm to within the mitochondrion where the β-oxidation process takes place. l-Carnitine is a superoxide scavenger and an antioxidant that possesses an anti-ischemic action and a stabilizing effect on cell membranes. It may be of help in liver ischemia reperfusion injury. Results regarding the effects of l-carnitine on liver ischemia and reperfusion injury are few and conflicting. Objective: The aim of this study was to investigate the efficacy of exogenous l-carnitine on lipid peroxidation and protecting liver at different stages of experimental total warm hepatic ischemia-reperfusion (TWHIR) procedure in rats. Methods: This experimental study in healthy, weanling, male Wistar rats (weighing 180–200 g) was conducted at the Experimental Animal Research Laboratory of the Faculty of Medicine of Mersin University, Mersin, Turkey. Rats were randomly divided into 5 groups: (A) Control group; (B) TWHIR procedure only; (C) l-carnitine administered 2 hours before the TWHIR procedure; (D) l-carnitine administered just before the TWHIR procedure; and (E) l-carnitine administered after total warm hepatic ischemia but just before the reperfusion procedure. Total warm hepatic ischemia (via the Pringle maneuver) and reperfusion were performed for 45 and 30 minutes, respectively. l-Carnitine (200 mg/kg) was administered intravenously. At the end of each procedure a blood sample was drawn and total hepatectomy was performed following reperfusion. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels of both plasma and liver tissue, total antioxidant capacity (TAOC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in plasma, and histopathologic examination were analyzed to assess lipid peroxidation and damage in liver tissue. Results: Thirty-four rats (mean [SD]age, 59.26 [1.2]days; mean [SD] weight, 194.1 [5.1] g) were used in the study. There was a significant difference observed between groups A (n = 5) and B (n = 5) for all evaluation parameters. The TWHIR procedure performed in group B was associated with significant increases versus baseline in ALT, AST, MDA, and MPO in plasma, and MDA and MPO in liver tissue, but a significant decrease of TAOC in plasma. ALT, AST, serum and liver MDA, and MPO levels of group B were significantly higher than all groups administered l-carnitine. l-Carnitine administration between total warm hepatic ischemia and reperfusion was associated with a significant attenuation in all parameters. The liver MDA levels of groups C (n = 8) and D (n = 8) were significantly lower than that of group E (n = 8) (mean [SD]: C, 16.53 [3.32] and D, 18.28 [1.67] vs E, 23.05 [3.52]; P = 0.001 and P = 0.016, respectively). The mean (SD) liver MPO level of group C (1.09 [0.16]) was significantly lower than that of groups D (2.12 [0.25]) and E (2.11 [0.28]) (both, P = 0.001). The TAOC of group B (0.77 [0.12]) was significantly lower than that of groups C (1.34 [0.19]) and D (1.08 [0.20]) ( P = 0.001 and P = 0.015, respectively). The TAOC of group C was significantly higher than that of the other l-carnitine groups (E, 0.94 [0.13]) ( P = 0.023 vs group D; and P = 0.001 vs group E). Histopathologic scores of groups A, C, and E were significantly lower than that of group B, but the difference between groups B and D was not statistically significant. Conclusions: In this experimental study, administration of exogenous l-carnitine was associated with significantly decreased lipid peroxidation in plasma and liver tissue when administered prior to a TWHIR procedure. In addition, l-carnitine seemed to be more effective with regard to decreasing lipid peroxidation in liver tissue when administered before warm hepatic ischemia. l-Carnitine was associated with significantly decreased leukocyte sequestration in plasma and liver tissue. A significant increase in TAOC was associated with l-carnitine administered prior to ischemia. These observations suggest that l-carnitine might have a protective effect against ischemia-reperfusion injury in rat liver tissue.

Effect of Genistein with Carnitine Administration on Lipid Parameters and Obesity in C57Bl/6J Mice Fed a High-Fat Diet

Soy products are mainly composed of proteins, phytochemicals such as isoflavones, soy lipids, and carbohydrates. It is unclear whether an individual component alone or a combined effect of multiple bioactive compounds contributes to the beneficial properties of soy. We investigated the effect of dietary genistein (the principal soy isoflavone) alone and combined with L-carnitine to evaluate possible synergistic effects on the intentionally induced prediabetic state characterized by insulin resistance and obesity in C57Bl/6J mice fed a high-fat diet (HD). In the HD-alone group, abdominal and back fat relative to total body weight were significantly higher compared with other groups including those fed normal diet (ND). Among the HD groups, final weight gains of the HD plus genistein (HD+G) and HD plus genistein plus L-carnitine (HD+G+C) groups were lower compared with that of the control (HD-alone). Especially in liver, the results showed that genistein with carnitine transcriptionally up-regulated expressions of acyl-coenzyme A synthetase (ACS) and carnitine palmitoyltransferase-I (CPT-I) by approximately 50% and 40%, respectively, compared with genistein alone. However, the up-regulation of CPT-I did not directly reflect the enzyme activity of CPT-I. On the other hand, the effects of genistein and genistein with carnitine on the expressions of ACS and CPT-I in muscle were not significant. Our study suggests that genistein with carnitine exerts anti-obesity effects, probably by modulating peroxisome proliferator-activated receptor-associated genes. However, further work is needed to elucidate the possible mechanisms by which genistein and carnitine intervene.

Metabolic Treatment with L-Carnitine in Acute Anterior ST Segment Elevation Myocardial Infarction

Background: Administration of L-carnitine in patients with anterior acute myocardial infarction (AMI) prevents left ventricular remodeling. Current study was aimed to assess the effect of L-carnitine administration on mortality and heart failure in patients with anterior AMI. Methods: CEDIM 2 trial was a randomized, double-blind, multicenter, placebo-controlled trial planned to enroll 4,000 patients with acute anterior AMI. The trial was interrupted after the enrolment of 2,330 patients because of the lower than expected enrolment rate. The primary end point was a composite of death and heart failure at 6 months; 5-day mortality was the secondary end point. Results: During the 6-month follow-up, the primary end-point was not significantly different between the L-carnitine and placebo group (9.2 vs. 10.5%, p = 0.27). A reduction in mortality was seen in the L-carnitine arm on day 5 (secondary end-point) from randomization (HR = 0.61, 95% CI 0.37–0.98, p = 0.041). Conclusions: In CEDIM 2 trial L-carnitine therapy led to a reduction in early mortality (secondary end-point) without affecting the risk of death and heart failure at 6 months in patients with anterior AMI, leading to a non-significant finding with respect to the primary end-point.