L-carnitine Treatment Research Articles

L-carnitine prevents metabolic steatohepatitis in obese diabetic KK-Ay mice.

Pharmacological treatment for metabolic syndrome-related non-alcoholic steatohepatitis has not been established. We investigated the effect of L-carnitine, an essential substance for β-oxidation, on metabolic steatohepatitis in mice. Male KK-Ay mice were fed a high-fat diet (HFD) for 8weeks, with supplementation of L-carnitine (1.25mg/mL) in drinking water for the latter 4weeks. Serum total carnitine levels were decreased following HFD feeding, whereas the levels were reversed almost completely by L-carnitine supplementation. In mice given L-carnitine, exacerbation of hepatic steatosis and hepatocyte apoptosis was markedly prevented even though HFD feeding was continued. Body weight gain, as well as hyperlipidemia, hyperglycemia, and hyperinsulinemia, following HFD feeding were also significantly prevented in mice given L-carnitine. High-fat diet feeding elevated hepatic expression levels of carnitine palmitoyltransferase 1A mRNA; however, production of β-hydroxybutyrate in the liver was not affected by HFD alone. In contrast, L-carnitine treatment significantly increased hepatic β-hydroxybutyrate contents in HFD-fed mice. L-carnitine also blunted HFD induction in sterol regulatory element binding protein-1c mRNA in the liver. Furthermore, L-carnitine inhibited HFD-induced serine phosphorylation of insulin receptor substrate-1 in the liver. L-carnitine decreased hepatic free fatty acid content in 1week, with morphological improvement of swollen mitochondria in hepatocytes, and increases in hepatic adenosine 5'-triphosphate content. L-carnitine ameliorates steatohepatitis in KK-Ay mice fed an HFD, most likely through facilitating mitochondrial β-oxidation, normalizing insulin signals, and inhibiting de novo lipogenesis in the liver. It is therefore postulated that supplementation of L-carnitine is a promising approach for prevention and treatment of metabolic syndrome-related non-alcoholic steatohepatitis.

L-carnitine protects human hepatocytes from oxidative stress-induced toxicity through Akt-mediated activation of Nrf2 signaling pathway.

In our previous study, l-carnitine was shown to have cytoprotective effect against hydrogen peroxide (H2O2)-induced injury in human normal HL7702 hepatocytes. The aim of this study was to investigate whether the protective effect of l-carnitine was associated with the nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) pathway. Our results showed that pretreatment with l-carnitine augmented Nrf2 nuclear translocation, DNA binding activity and heme oxygenase-1 (HO-1) expression in H2O2-treated HL7702 cells, although l-carnitine treatment alone had no effect on them. Analysis using Nrf2 siRNA demonstrated that Nrf2 activation was involved in l-carnitine-induced HO-1 expression. In addition, l-carnitine-mediated protection against H2O2 toxicity was abrogated by Nrf2 siRNA, indicating the important role of Nrf2 in l-carnitine-induced cytoprotection. Further experiments revealed that l-carnitine pretreatment enhanced the phosphorylation of Akt in H2O2-treated cells. Blocking Akt pathway with inhibitor partly abrogated the protective effect of l-carnitine. Moreover, our finding demonstrated that the induction of Nrf2 translocation and HO-1 expression by l-carnitine directly correlated with the Akt pathway because Akt inhibitor showed inhibitory effects on the Nrf2 translocation and HO-1 expression. Altogether, these results demonstrate that l-carnitine protects HL7702 cells against H2O2-induced cell damage through Akt-mediated activation of Nrf2 signaling pathway.

Melatonin and L-carnitin improves endothelial disfunction and oxidative stress in Type 2 diabetic rats

Vascular dysfunction is thought to play a major role in the development of diabetic cardiovascular disease. The roles of endothelial dysfunction, oxidative stress, and dyslipidemia will be considered. Melatonin as well as L-carnitine were shown to possess strong antioxidant properties. Diabetes induced with high fat diet (for 8 weeks) and multipl low doses intraperitoneal injection of STZ (twice, 30mg/kg/d i.p). The diabetic animals were randomly assigned to one of the experimental groups as follows: Control group (C), high fat diet (HFD), STZ-induced diabetic group (HFD+STZ) , HFD+STZ diabetic group received melatonin (10mg/kg/d i.p), HFD+STZ diabetic group received L-carnitine (0.6g/kg/d i.p), and HFD+STZ diabetic group received glibenclamide (5mg/kg/d, oral). The serum fasting blood glucose, insulin, total cholesterol, HDL- cholesterol, LDL-cholesterol, triglyceride and malondialdehyde (MDA) levels were tested. Acetylcholine induced endothelium-dependent relaxation and sodium nitroprusside induced endothelium-independent relaxation were measured in aortas for estimating endothelial function. Also, glutathione peroxidase (GPx), superoxide dismutase (SOD) and nitric oxide (NO) levels activities were determined in rat liver. According to our results melatonin and L-carnitine treatment decreased fasting blood glucose, total cholesterol, and LDL levels. MDA levels significantly decreased with the melatonin treatment whereas SOD levels were not significantly changed between the groups. The results suggest that especially melatonin restores the vascular responses and endothelial dysfunction in diabetes.

Effect of L-Carnitine in Patients With Liver Cirrhosis on Energy Metabolism Using Indirect Calorimetry: A Pilot Study.

BackgroundL-carnitine supplementation has been suggested to show several favorable effects on patients with liver cirrhosis (LC). However, there have been no reports regarding the effect of L-carnitine on energy metabolism in patients with LC using indirect calorimetry which is a well-established method for assessing the degree of liver malnutrition. We examined the effect of L-carnitine in patients with LC on energy metabolism using indirect calorimetry.MethodsA total of 13 LC patients who are scheduled to be treated with L-carnitine (1,800 mg/day) were analyzed in this study. None of the patients previously received L-carnitine. An evaluation of the nutritional status was performed at the initiation of L-carnitine therapy and after 4 weeks of L-carnitine therapy. We evaluated the effect of L-carnitine on the nutritional status and energy metabolism by comparing various clinical variables at these two time points. In addition, the changes in the nutritional status of the patients were also evaluated using indirect calorimetry.ResultsAfter 4 weeks of L-carnitine treatment, for all cases, the mean substrate oxidation rates of carbohydrate (%C) increased from 37.6% to 48.2%, the mean substrate oxidation rates of fat (%F) decreased from 40.2% to 31.9% and the mean substrate oxidation rates of protein (%P) decreased from 22.2% to 19.9%. In a subgroup analysis of patients with baseline non-protein respiratory quotient (npRQ) < 0.85, the mean %C increased from 15.3% to 34.2%, the mean %F decreased from 59.9% to 45.1%, and the mean %P decreased from 24.8% to 20.6%. After 4 weeks of L-carnitine treatment, for all cases (n = 13), the mean value of npRQ increased in comparison with the baseline levels, although the difference was not significant (0.868 ± 0.060 vs. 0.838 ± 0.097, P = 0.19). Conversely, in patients with baseline npRQ < 0.85, the npRQ value significantly increased after 4 weeks treatment of L-carnitine compared with the baseline levels (0.827 ± 0.030 vs. 0.760 ± 0.043, P = 0.016).ConclusionL-carnitine supplementation can be useful for improving energy metabolism, especially in patients who have an advanced LC status and lower baseline npRQ values.

生殖医学における低反応レーザー治療（LLLT）の役割

We evaluated the efficacy of supplements treatment (L-carnitine and melatonin) and low reactive level laser therapy (LLLT) and the integrated medicine program for IVF failures. After L-carnitine treatment blastocyst rate was significantly increased (37.0 % vs 60.8 %, P<0.01). After melatonin treatment good embryo rate (45.2 % vs 63.0 %, P<0.01), blastocyst rate (28.3 % vs 54.4 %, P<0.01) and good blastocyst rate (29.4 % vs 67.7 %, P<0.05) were significantly increased. After LLLT, the numbers of MII oocytes (1.7 vs 2.0, P<0.05) and the numbers of fertilized oocytes (1.6 vs 1.8, P<0.05) were significantly increased. Good embryo rate was significantly increased (64.0 % vs 79.0 %, P<0.05). In hormone supplemented frozen thawed ET cycles, pregnancy rate of day 3 embryos was significantly increased (6.7 % vs 17.8 %, P<0.05) after LLLT. And after the integrated medicine program, pregnancy rate was significantly increased (12.0 % vs 23.7 %, P<0.01).

Effect of Pre-Conception Coenzyme Q10 and L-Carnitine Treatments on Ovulatory Response, Genital Characteristics and in vitro Embryo Characteristics in Rabbits

Effect of Pre-Conception Coenzyme Q10 and L-Carnitine Treatments on Ovulatory Response, Genital Characteristics and in vitro Embryo Characteristics in Rabbits

47 EFFECT OF L-CARNITINE TREATMENT DURING OOCYTE MATURATION ON THE POST-THAW DEVELOPMENT OF PORCINE EMBRYOS VITRIFIED AT THE PRONUCLEAR STAGE

The extreme cryo-sensitivity of porcine oocytes and embryos is attributed to their endemically high content of cytoplasmic lipid droplets. In attempts to improve the cryo-tolerance of porcine embryos, various strategies have been used to reduce the amount of lipid droplets present in the cytoplasm before vitrification. Recently, the cryo-tolerance of bovine oocytes vitrified at the metaphase II stage was improved by supplementing in vitro maturation (IVM) medium with l-carnitine (LC), a stimulator of lipid metabolism (Chakitisakul et al. 2013 Theriogenology 79, 590–598). The objective of this study was to determine the effect of supplementing IVM medium with LC on the post-thaw development of porcine embryos vitrified at the pronuclear stage. Oocytes recovered from the ovaries of prepubertal gilts were matured in modified porcine oocyte medium supplemented with 0 (control) or 12 mM LC during the final 22 h of IVM. Following IVF, presumptive zygotes were cultured in porcine zygote medium-3. At the pronuclear stage, cohorts of embryos from each group were either vitrified using a solid surface vitrification procedure (Somfai et al. 2009 Biol. Reprod. 80, 42–49) or cultured for 7 d without being vitrified. Vitrified zygotes were subsequently warmed and cultured for 7 d. The rates of cleavage, blastocyst formation, and hatching were recorded, and all blastocysts were stained to determine the total cell numbers. Three replicates were performed. Proportional data were arcsine transformed and subjected to ANOVA, and cell number data were analysed by t-test. The post-thaw survival rates of the embryos that were vitrified did not differ between the groups (control: 95.7%; LC: 97.1%; P &gt; 0.05). There were no significant effects of LC treatment or vitrification on the rates of cleavage, blastocyst formation, and hatching (Table 1). Vitrified embryos derived from LC-treated oocytes produced blastocysts with fewer cells than vitrified embryos derived from untreated oocytes (Table 1; P &lt; 0.05). In contrast to previous findings in other species, the results indicate that supplementing IVM medium with LC did not enhance the post-thaw development of porcine embryos vitrified at the pronuclear stage. Table 1.Effect of l-carnitine (LC) treatment and vitrification on porcine embryo development C. Grupen was supported by an OECD Fellowship.

EFFECT OF ORAL L-CARINITINE ADMINISTRATION ON PRODUCTIVE AND REPRODUCTIVE PERFORMANCES OF CROSSBREED CATTLE

The objective of this study was to evaluate the effects of oral L-carnitine (LC) administration on milk yield and composition, estrous activity and reproduction performance of crossbreed cows. A total of 30 crossbreed cows at early post-partum, weighing 432.7±23.5 kg LBW, aging 3.5-4 years and in 1-3 parities were divided into two similar groups according to LBW and age. Cows in the 1st group were fed a basal diet and was considered as a control group (G1). While, cows in the 2nd group (G2) were fed the same diet and treated orally with 3 g LC/cow/day for 120 days postpartum. Cows were machine milked and milk yield was calculated as actual (AMY) or 4% fat corrected milk (FCMY) yield. Milk composition and somatic cell count (SCC) were determined. Estrus was detect and cows in heat were artificially inseminated. Then, number and length of estrous cycles from calving up to conception was recorded. Postpartum 1st estrus (PPFEI) and 1st service (PPFSI) intervals, number of services per conception (NSC), service period length (SPL), days open (DO) and conception rate (CR%) were calculated. Pregnancy was diagnosed by rectal palpation on day 60 post-insemination. Results show that daily milk yield as AMY or FCMY of cows increased (P<0.05) by about 19.3% in G2 than in G1. Percentage of fat and protein in milk increased (P<0.05), while SCC decreased (P<0.05) by about 16.9% in milk of G2 as compared to G1. Average number of estrus cases and estrous cycles/cow was lower (P<0.05) in G2 than in G1. Average P4 concentration and P4 peak during the estrous cycle was higher (P<0.05) in G2 than in G1. Average P4 concentration during PPFEI was lower (P<0.05) in G2 than in G1. Average of PPFEI, PPFSI, SPL, DO and NSC were lower (P<0.05) in G2 than in G1. CR was higher (P<0.05) in G2 (93.33%) than in G1 (66.67%). In conclusion, the present study indicated beneficial effects of L-carnitine treatment (3 g/cow) for 120 days during early lactation period on milk production and reproductive performance of crossbreed cows during the first four months of lactation.

Effects of L-carnitine supplementation on nutritional, immunological, and cardiac parameters in hemodialysis patients: a pilot study

L-carnitine is an essential compound that facilitates the transport of long-chain fatty acid across the inner mitochondrial membrane for β-oxidation. However, the effect of L-carnitine supplementation remains to be fully explored in patients with chronic kidney disease. We aimed in this study to determine the multidirectional effects of L-carnitine supplementation on clinical parameters in more detail. We orally administered L-carnitine to maintain serum-free carnitine levels within the normal range (30 to 70 μmol/L) for 6 months in 21 hemodialysis (HD) patients (age, 74 ± 11 years; time on HD, 60 ± 84 months). L-carnitine supplementation significantly increased serum transferrin from 155 ± 41 to 175 ± 48 mg/dL (p < 0.01) and retinol-binding protein from 8.9 ± 2.5 to 10.0 ± 3.4 mg/dL (p < 0.05). The triceps skinfold thickness was also significantly increased (p < 0.05), while the skeletal muscle mass in limbs and handgrip strength was not. L-carnitine enhanced natural killer (NK) cell activity at the E (effector cell)/T (target cell) ratio of 20:1 from 17.3 ± 14.1 to 20.8 ± 17.7 % (p < 0.01). In addition, L-carnitine improved left ventricular functional shortening (p < 0.01) with a significant decrease of brain natriuretic peptide (BNP) from 621.4 ± 666.8 to 412.0 ± 426.0 pg/mL (p < 0.05). These findings suggest that oral L-carnitine treatment improves immunological and cardiac markers in HD patients. In contrast, L-carnitine did not change the skeletal mass-related parameters during the 6-month follow-up.

The effects of acetyl L-carnitine treatment on cognitive and memory function in epileptic patients under antiepileptic medication

The effects of acetyl L-carnitine treatment on cognitive and memory function in epileptic patients under antiepileptic medication

Protective effect of L-carnitine in cyclophosphamide-induced germ cell apoptosis.

Cyclophosphamide (CP) is a widely used anti-cancer agent; however, it can also induce serious male infertility. There are currently no effective drugs to alleviate this side-effect. L-Carnitine has been used to treat male infertility, but whether it can be used to protect against CP-induced male infertility is still unclear. This study aims to explore the effect and mechanism of L-carnitine in male infertility induced by CP. CP was used to establish an animal model. After three weeks of treatment, rats were sacrificed and testis and serum were harvested for further evaluation. Testosterone and estrogen levels were measured by enzyme-linked immunosorbent assay (ELISA). Testicular injury was examined by hematoxylin and eosin (H & E) staining, and germ-cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression of LC3 and Beclin-1 was examined by immunohistochemistry, Western blot, and real-time polymerase chain reaction (PCR), respectively. Compared with the CP group, L-carnitine significantly increases sperm motility, viability, and testosterone level (P<0.05). Western blot and real-time PCR results showed that L-carnitine treatment can significantly up-regulate the LC3-II and Beclin-1 expression in the CP+L-carnitine group when compared with the control group (P<0.05). In addition, TUNEL-positive cells were also more numerous in the CP group; however, L-carnitine can effectively retard cell apoptosis in the CP+L-carnitine group. In conclusion, L-carnitine contributes to the inhibition of cell apoptosis and the modulation of autophagy in protecting CP-induced testicular injury. These results suggest the applicability of L-carnitine in the treatment of male infertility.

L-carnitine reduces acute lung injury in experimental biliary obstruction.

Objectives:To investigate the protective effects of L-carnitine (LC) on lungs in an experimental obstructive jaundice (OJ) model.Methods:This was conducted for 2 months between May 2011 and July 2011 at Suleyman Demirel University School of Medicine Experimental and Clinical Research Center, Isparta, Turkey. Thirty-eight Wistar-Albino rats with an average weight of 250-300 g were divided into 3 groups of control, OJ, and OJ + L-carnitine treatment (LCT). L-carnitine was injected intravenously into the tail vein at a dose of 50 mg/kg/day for 10 days to the LCT group. Animals were sacrificed 10 days later. Enzyme levels were measured in the lung tissue; malondialdehyde, myeloperoxidase (MPO), glutathione peroxidase (GSH-Px), catalase, and superoxide dismutase. Tumor necrosis factor-alfa, interleukin 6 (IL-6), IL-8, and C-reactive protein levels were studied in plasma samples. Histopathological changes in the lungs were examined.Results:There was a decreased in GSH-Px, MPO, and IL-8 levels (p<0.05) in the LCT group. The histopathological examination showed that neutrophil leukocyte infiltration and edema formation decreased and destruction of lung parenchyma disappeared following the treatment with LC (p<0.05).Conclusion:L-carnitine has a protective effect against lung damage due to experimental obstructive jaundice, possibly by altering anticytokine and antioxidant activity, and by decreasing the neutrophil migration.

Serum level of taurine would be associated with the amelioration of minimal hepatic encephalopathy in cirrhotic patients.

A variety of treatment modalities including L-carnitine have been tried for cirrhotic patients with minimal hepatic encephalopathy (MHE), which improved MHE for some patients, but were not effective for the other patients. We aimed to identify pre-therapeutic independent factors to predict the amelioration of MHE after L-carnitine treatment. We performed a prospective cohort study on a total of 64 consecutive outpatients of cirrhotic patients who underwent blood biochemical examinations and neuropsychiatric (NP) test at Kobe University Hospital. MHE patients diagnosed by the NP test were p.o. administrated L-carnitine for 3months. The patients with and without MHE amelioration were compared, and the independent factors were statistically examined. Predictive scoring systems of the amelioration of MHE were established using multivariate logistic regression. The amelioration of MHE was found in 45.8% of MHE patients. Serum taurine before the treatment was the best predictive factor of the amelioration of MHE (P = 0.046). The predictive model using serum taurine discriminated well between patients with and without the amelioration of MHE (area under the receiver-operator curve, 0.748; 95% confidence interval, 0.531-0.901). The predictive scores of the amelioration of MHE enable the patient-specific probability to be easily looked up. Serum taurine before L-carnitine treatment was shown to be an independent factor associated with the amelioration of MHE 3months after the treatment. The easy pre-therapeutic prediction of MHE amelioration after L-carnitine treatment would help in improving awareness of the selection of MHE patients with good response to L-carnitine, thus being beneficial from a financial perspective.

Palmitoleic acid induces the cardiac mitochondrial membrane permeability transition despite the presence of l-carnitine

Although palmitoleic acid (C16:1) is associated with arrhythmias, and increases in an age-dependent matter, the effects of l-carnitine, which is essential for the transport of long-chain fatty acids into the mitochondria, are unclear. It has been postulated that l-carnitine may attenuate palmitate (C16:0)-induced mitochondrial dysfunction and the apoptosis of cardiomyocytes. The aim of this study was to elucidate the activity of l-carnitine in the prevention of the palmitoleic acid-induced mitochondrial membrane permeability transition and cytochrome c release using isolated cardiac mitochondria from rats. Palmitoleoyl-CoA-induced mitochondrial respiration was not accelerated by l-carnitine treatment, and this respiration was slightly inhibited by oligomycin, which is an inhibitor of ATP synthase. Despite pretreatment with l-carnitine, the mitochondrial membrane potential decreased and mitochondrial swelling was induced by palmitoleoyl-CoA. In the presence of a combination of l-carnitine and tiron, a free radical scavenger, there was attenuated mitochondrial swelling and cytochrome c release following palmitoleoyl-CoA treatment. We concluded that palmitoleic acid, but not palmitate, induces the cardiac mitochondrial membrane permeability transition despite the presence of l-carnitine.

A case of late-onset riboflavin responsive multiple acyl-CoA dehydrogenase deficiency (MADD) with a novel mutation in ETFDH gene

We report a novel mutation in the electron transfer flavoprotein dehydrogenase (EFTDH) gene in an adolescent Chinese patient with late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD) characterized by muscle weakness as early symptom. At the age of 9years, the patient experienced progressive muscle weakness. Blood creatine kinase level and aminotransferase were higher than normal. The muscle biopsy revealed lipid storage myopathy. Serum acylcarnitine and urine organic acid analyses were consistent with MADD. Genetic mutation analysis revealed a compound heterozygous mutation in EFTDH gene. The patients showed good response to riboflavin and l-carnitine treatment.

Mitochondrial dysfunction in Kennedy's disease: a new pharmacological target?

Mitochondrial impairment and elevated oxidative stress have been implicated in the pathogenesis of Kennedy's disease. However, there is still no study describing the mitochondrial nutrient management in patients with Kennedy's disease. We assessed the clinical and electrophysiological features in a patient with Kennedy's disease. This patient was diagnosed by genetic analysis. We also measured the plasma 8-hydroxydeoxyguanosine (8-OHdG) levels of the patient and his family members using commercial enzyme-linked immunosorbent assay (ELISA). Treatment with intravenous L-carnitine (2 g/day) for the patient was started on admission, followed by two weeks. Routine laboratory tests revealed a severe elevation of creatine kinase (CK) (606.5 U/L; normal value: 15-170 U/L). Sequencing of the first exon of androgen receptor (AR) revealed an increased number of CAG repeat (50; the normal range from 10-36) in the patient. Plasma 8-OHdG level in the patient was relatively elevated (34.68±1.01 ng/mL) compared with the female carriers and non-carriers. Two weeks after L-carnitine treatment, we observed a reduction of approximately 40% in CK level (391 U/L) in the patient. Oxidative stress resulting from mitochondrial dysfunction could be involved in Kennedy's disease. Targeting the mitochondrial dysfunction in Kennedy's disease may have significant therapeutic potential.

Effect of L-carnitine enrichment on the rotifer and influences on clownfish larvae

Enrichment has shown considerable influence on the population growth, reproduction and individual growth of rotifer (Brachionus plicatilis Müller, 1786) and its utility on the clownfish larvae (Amphiprion ocellaris Cuvier 1830). Using the culture medium of microalgae (Nannochloropsis salina D.J. Hibberd 1981) as the control, rotifers were enriched by dissolving in S-presso (for short term enrichment) or L-carnitine supplements. The study was conducted in three replicates for five and 10 days of batch culture. On day-4, the population density of rotifers exposed to 1, 10 and 100 mg l -1 L-carnitine was significantly increased (p&lt;0.001) by 43, 39 and 54%, respectively, compared to the control. The population density in these three treatments also increased on day-2, day-3 and day-5 compared to the 1000 mg L-1 treatment (p&lt;0.05) and control (p&lt;0.05). The body length (p&lt;0.001) and width (p&lt;0.05) were significantly reduced in the 1000 mgL-1 treatment compared to the control. The mean values of total unsaturated fatty acids (PUFA's, HUFA's and n-3 fatty acids) and the ratio of n-3/n-6, DHA/EPA, EPA/AA were significantly higher (p&lt;0.05) in the rotifers enriched with L-carnitine compared to S-presso and algae. Larvae fed using rotifer enriched with L-carnitine gained the maximum growth (65.7±1 mg), followed by those enriched with S-presso (42.2±0 mg). In L-carnitine treatment, metamorphosis took only 9 days, followed by the control. In L-carnitine and S-presso units, the clownfish larvae took only three days for the first pigmentation compared to four days in N. salina (control) and 10 days with S-presso. Rotifers enriched with L-carnitine showed the highest survival rate (70 %) of the clownfish followed by the control (68%) and S-presso (52%). The results suggested that L-carnitine could be a positive factor to enhance the rotifer production and also its utilization in clownfish larval culture.

Effect of L-carnitine supplementation on maturation and early embryo development of immature mouse oocytes selected by brilliant cresyle blue staining.

The present study was designed to investigate the effect of L-carnitine treatment during IVM on nuclear and cytoplasmic maturation of immature oocytes selected by Brilliant Cresyle Blue (BCB) staining, and their subsequent developmental competence. Compact cumulus-oocyte complexes (COCs) were collected from NMRI mice ovaries and stained with BCB staining. BCB+ (colored cytoplasm) oocytes were then cultured in tissue culture medium (TCM) 199 with 0.0, 0.3 and 0.6 mg/ml L-carnitine. The both L-carnitine concentrations significantly increased the intracellular glutathione (P<0.001), nuclear maturation (P<0.01) and expression levels of cyclin-dependent kinase1 (CDK1) (P<0.05). Moreover, treated oocytes with 0.6 mg/ml L-carnitine showed increased (P < 0.05) expression of mitogen-activated protein kinase1 (MAPK1) mRNA. Also, adding L-carnitine (0.6 mg/ml) to IVM medium significantly increased the cleavage rate (P<0.05). The blastocyst development rate (BDR) in the both L-carnitine treated groups was significantly higher (P<0.001) than the control group. L-carnitine had no significant effect on total blastocyst cell numbers. These data indicated that L-carnitine supplementation during IVM of immature BCB+ oocytes improved preimplantation developmental competence of oocytes after IVF, probably by accelerating cytoplasmic and nuclear maturation of oocytes. It may provide a novel approach to improving ART outcomes in infertile couples.

The effect of vitamin E and L-carnitine against methotrexate-induced injury in rat testis

Methotrexate (MTX), used commonly as an antimetabolite drug in cancer therapy, leads to acute toxic side effects in tissues or organs containing rapidly dividing cells, such as bone marrow, gastrointestinal mucosa, and seminiferous tubules. In this study, we investigated the protective effects of vitamin E and L-carnitine against MTX-induced injury in rat testis. Rats were divided into 4 groups, including the control group. The study took 17 days and the animals received daily doses of 0.5 mL/kg saline, 250 mg/kg vitamin E, or 500 mg/kg L-carnitine intraperitoneally. The experimental groups received 20 mg/kg methotrexate intraperitoneally on days 3 and 10. Weight loss, testicular weight loss and marked histological injuries, increased malondialdehyde levels, and decreased superoxide dismutase levels were only observed in the MTX-treated groups. Vitamin E and L-carnitine treatments did not affect MTX-induced weight loss or testicular weight loss, but they inhibited MTX-induced testicular histological injuries. Vitamin E and L-carnitine treatments suppressed the increases in malondialdehyde levels and the decreases in superoxide dismutase levels. Vitamin E and L-carnitine treatments decreased MTX-induced testicular histological injuries, and these results were supported by biochemical measurements.

Combined Tamoxifen and L-Carnitine Therapies for the Treatment of Idiopathic Male Infertility Attending Intracytoplasmic Sperm Injection: A Randomized Controlled Trial

ABSTRACTAimThe aim of the present study is to evaluate the fertility outcomes of intracytoplasmic sperm injection (ICSI) as well as sperm count, motility and morphology in couples with infertile male partners exhibiting idiopathic oligoasthenozoospermia (OA) and treated with tamoxifen citrate and/or L-carnitine.Materials and methodsIn this randomized controlled trail, couples with female cause of infertility were excluded. Only couples with male cause of infertility with idiopathic OA were admitted to this study and randomly assigned into four different groups of treatments as follow: Group A (n = 45) received an anti-estrogen compound (tamoxifen 20 mg/day), group B (n = 20) received L-carnitine (1000 mg/day), group C (n = 34) received tamoxifen 20 mg/day plus L-carnitine 1000 mg/day, whereas group D (n = 29) received placebo. Treatments were continued for 3 to 6 months.ResultsTreatment groups of A, B, and C showed an overall improvement in the tested parameters of sperm when compared to the control group that showed an overall reduction in those parameters after termination of the treatment. In this context, sperm count increased from 7.58 ± 2.93 × 106/ml before treatment to 10.81 ± 1.84 × 106/ml after treatment in group A (p = 0.016). Similarly, sperm count increased from 5.32 ± 2.09 × 106/ml to 8.92 ± 2.29 × 106/ml in group C (p = 0.01). Patients from group C did not only have an improved total motility of sperm from 8.03 ± 1.59% to 13.78 ± 3.85% (p = 0.045) but also an improved sperm normal morphology from 0.88 ± 0.45% to 1.99 ± 0.71% (p = 0.026). Patients from group A or C exhibited an improved ICSI outcomes when compared to those in patients from group B or D (48.9 or 48.3 vs 16.6 or 20, respectively, p = 0.46).ConclusionIt is concluded that administration of tamoxifen and L-carnitine can improve both sperm parameters of fertility and ICSI outcomes. Combined tamoxifen and L-carnitine treatments result in maximum therapeutic effect in men with idiopathic OA.How to cite this articleHaje M, Naoom K. Combined Tamoxifen and L-Carnitine Therapies for the Treatment of Idiopathic Male Infertility Attending Intracytoplasmic Sperm Injection: A Randomized Controlled Trial. Int J Infertil Fetal Med 2015;6(1):20-24.