Administration Of L-carnitine Research Articles

Anti-pruritic effect of L-carnitine against chloroquine-induced pruritus mediated via nitric oxide pathway.

Pruritus, or itching, is a distressing symptom associated with various dermatological and systemic diseases. L-carnitine (βeta hydroxy-γ-tri methyl amino-butyric acid), is a naturally occurring substance, it controls numerous physiological processes. The present research aims to identify L-carnitine for its anti-pruritic effect via nitric oxide-dependent mechanism. Chloroquine-induced pruritus serves as an experimental model to investigate possible therapeutic interventions. In this study, we evaluated the efficacy of L-carnitine in combating oxidative stress, nitric oxide, and inflammatory cytokines in a chloroquine-induced pruritus model. L-carnitine treatment significantly reduced scratching behavior compared to the disease group (***P < 0.001 vs. chloroquine group), indicating its antipruritic potential. The markers of oxidative stress, GST, GSH, Catalase, and LPO were dysregulated in the disease model, but administration of L-carnitine restored GST, GSH, and Catalase levels and decreased LPO levels (***P < 0.001 vs. chloroquine group), thereby alleviating oxidative stress. L-carnitine also reduced nitric oxide synthase (NOS) activity, suggesting that it modulates nitric oxide signaling pathways involved in pruritus. In addition, L-carnitine lowered levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), inflammatory marker nuclear factor kappa B (p-NFκB) and also reduces an inflammatory enzyme, cyclooxygenase-2 (COX-2), determined by ELISA (Enzyme-Linked Immunosorbent Assay) (***P < 0.001 vs. chloroquine group). It downregulates nNOS mRNA expression confirmed by real-time polymerase chain reaction (RT-PCR). These findings highlight the therapeutic effects of L-carnitine in alleviating chloroquine-induced pruritus.

Potential utility of l-carnitine for preventing liver tumors derived from metabolic dysfunction-associated steatohepatitis.

Recent reports have unveiled the potential utility of l-carnitine to alleviate metabolic dysfunction-associated steatohepatitis (MASH) by enhancing mitochondrial metabolic function. However, its efficacy at preventing the development of HCC has not been assessed fully. l-carnitine (2g/d) was administered to 11 patients with MASH for 10 weeks, and blood liver function tests were performed. Five patients received a serial liver biopsy, and liver histology and hepatic gene expression were evaluated using this tissue. An atherogenic plus high-fat diet MASH mouse model received long-term l-carnitine administration, and liver histology and liver tumor development were evaluated. Ten-week l-carnitine administration significantly improved serum alanine transaminase and aspartate transaminase levels along with a histological improvement in the NAFLD activity score, while steatosis and fibrosis were not improved. Gene expression profiling revealed a significant improvement in the inflammation and profibrotic gene signature as well as the recovery of lipid metabolism. Long-term l-carnitine administration to atherogenic plus high-fat diet MASH mice substantially improved liver histology (inflammation, steatosis, and fibrosis) and significantly reduced the incidence of liver tumors. l-carnitine directly reduced the expression of the MASH-associated and stress-induced transcriptional factor early growth response 1. Early growth response 1 activated the promoter activity of neural precursor cell expressed, developmentally downregulated protein 9 (NEDD9), an oncogenic protein. Thus, l-carnitine reduced the activation of the NEDD9, focal adhesion kinase 1, and AKT oncogenic signaling pathway. Short-term l-carnitine administration ameliorated MASH through its anti-inflammatory effects. Long-term l-carnitine administration potentially improved the steatosis and fibrosis of MASH and may eventually reduce the risk of HCC.

L-carnitine decreases myocardial injury in children undergoing open-heart surgery: A randomized controlled trial

Myocardial injury in open-heart surgery is related to several factors including ischemia–reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes. The aim of this study was to study the effect of L-carnitine on myocardial injury in children undergoing open-heart surgery. This clinical trial was performed on 60 children with congenital heart disease (CHD) who underwent open-heart surgery. They were randomized into two groups: L-carnitine group who received L-carnitine 50 mg\\kg\\day once daily for 1 month before cardiac surgery and control group who received placebo for 1 month before cardiac surgery. Left ventricular cardiac function was assessed by conventional echocardiography to measure left ventricular ejection fraction (LVEF) and two-dimensional speckle tracking echocardiography (2D-STE) to determine left ventricular global longitudinal strain (2D-LV GLS). Blood samples were obtained pre-operatively at baseline before the administration of L-carnitine or placebo and 12 h post-operatively to measure the level of malondialdehyde (MDA), superoxide dismutase (SOD), fas, caspase-3, creatinine kinase-MB (CK-MB), and troponin I. L-carnitine group had significantly lower post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I), but they had significantly higher SOD post-operative level compared to the control group. In addition, post-operative LVEF and 2D-LVGLS were significantly lower in the control group compared to L-carnitine group. Conclusion: L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery. Trial registration: The clinical trial was registered at www.pactr.org with registration number PACTR202010570607420 at 29/10/2020 before recruiting the patients.What is Known:• Myocardial injury in open-heart surgery is related to several factors including ischemia–reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes.• L-carnitine was reported to have myocardial protective effects in rheumatic valvular surgery and coronary artery bypass graft (CABG) in adults; however, there is no evidence on its effectiveness in children undergoing open-heart surgery.What is New:• L-carnitine significantly lowered the post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I) in the treatment group.• L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery.

Mechanism of action of Wuzi Yanzong pill in the treatment of oligoasthenozoospermia in rats determined via serum metabolomics

ObjectiveTo investigate the mechanism of action of Wuzi Yanzong pill (WYP) in rats with oligoasthenozoospermia (OAZ) via metabolomics and to provide a possible basis for improving this WYP-based treatment. MethodsA rat model of OAZ was established by treating male Sprague–Dawley rats with glucosides from Tripterygium wilfordii Hook. F. Seventy-two rats were randomly divided into six groups: control, L-carnitine (positive control), model, and low-, medium-, and high-dose WYP groups. Rats in the experimental groups were treated with WYP for 4 weeks. At the end of the treatment period, sperm cell quality (density, motility, and viability) was assessed using a semen analysis system, mitochondrial membrane potential (MMP) was assessed using flow cytometry, and testicular injury was assessed using hematoxylin and eosin staining to validate the therapeutic effect of WYP in OAZ. Further, serum metabolomics-based analysis was performed using high-performance liquid chromatography-mass spectrometry to identify differential metabolic pathways and possible mechanisms of action of WYP in OAZ treatment. ResultsA rat model of OAZ was considered successfully-established after comparing the quality of spermatozoa in the model group to that in the control group. WYP-M and WYP-H treatments significantly improved sperm cell density, motility, and viability compared with those in the model group (all P < .05). Compared with the model group, both WYP-M and WYP-H treatments increased MMP values (P = .006 and P = .021 respectively), while there was no significant difference in the L-carnitine group. L-carnitine and WYP administration reversed damage to the testes to varying degrees compared with that in the model group. Further, 44 differential metabolites and four metabolic pathways, especially autophagy pathway, related to OAZ were identified via metabolomics. ConclusionsWYP improves sperm cell quality and MMP in OAZ primarily via autophagy regulation. These findings can be employed to improve the efficacy of WYP in humans.

Incidence of atrial fibrillation after esophageal cancer surgery with L-carnitine use: a preliminary single-group interventional study.

We aimed to investigate the POAF rate and blood FABP4 levels after perioperative L-carnitine administration in patients with esophageal cancer. L-carnitine (3g in three divided doses) was administered to 15 patients 2days before and 3days after surgery. POAF during the study period and blood FABP4 levels (ELISA) before and after L-carnitine administration were evaluated. Accurate 95% confidence intervals (CI) for POAF incidence and changes in blood FABP4 levels were calculated. The preoperative predicted POAF rate was calculated using an application for esophageal cancer. The correlation between FABP4 levels and the predicted POAF rate was analyzed using Pearson's coefficient (r). Thirteen patients completed this study. The predicted POAF rate was 24% (17%, 34%) (median; interquartile range). The actual incidence of POAF was 7.7% (95% CI: 0.2-36%). Blood FABP4 levels changed from 10.3 to 7.0ng/mL; the average change was -3.3 (95% CI: -6.6 to -0.1). A positive correlation was found between preoperative FABP4 levels and the predicted POAF rates (r = 0.564). The POAF rate after esophageal surgery was 7.7% for L-carnitine. L-carnitine may reduce blood FABP4 levels. This preliminary study will contribute to the planning of sample sizes in future randomized trials.

The Protective Role of L-carnitine on Psychosocial Stress-induced Changes in Gene Expression and Protein Levels of Matrix Metalloproteinases, Serum Corticosterone in a Rat Model.

Psychosocial stress (STS) is a common stress in modern societies. Chronic STS is associated with the impairment of a broad range of cognitive functions in humans and with prolonged abnormalities in memory. Matrix metalloproteinases (MMPs), a protein family of zinccontaining endopeptidases, are essential in neuro-inflammation and involved in neurodegenerative diseases. L-Car possessed neuroprotective, antioxidant, and anti-inflammatory properties and was shown to modulate MMPs. The current study aimed to examine the protective effect of L-Carnitine (L-CAR) on STSinduced changes in serum corticosterone levels, MMP-2, -9, and -12 protein and mRNA expression in the hippocampus as a possible mechanism for L-CAR protective effect on STS-induced memory impairment. The chronic STS and L-CAR (300 mg/kg/day, i.p) were simultaneously administered for 6 weeks to adult male Wistar rats. Serum corticosterone and protein levels of MMP-2, -9 and -12 were evaluated using ELISA. Real-Time PCR techniques were used to determine the mRNA levels of MMP-2, -9 and -12 in the hippocampus. The findings showed that serum corticosterone levels and MMP-2 and -9 protein levels were significantly increased (p<0.05) in the STS group compared to the control. Similarly, RT-PCR findings showed that the mRNA of those proteinases significantly increased (p<0.05) following the intruder method. On the other hand, the administration of L-CAR restored the alterations in corticosterone levels and MMPs gene and protein expression induced by chronic STS. STS induced elevations in corticosterone and MMP-2 and -9 levels in the hippocampus. L-CAR, on the other hand, exhibited protective effects against the STS-induced changes in MMP-2 and -9.

Incorporation of L-Carnitine in the OvSynch protocol enhances the morphometrical and hemodynamic parameters of the ovarian structures and uterus in ewes under summer climatic conditions

Heat stress negatively impacts the reproductive performance of sheep including the efficiency of estrous synchronization regimens. This study aimed to investigate the potential effects of L-Carnitine (LC) administration on the efficacy of the OvSynch protocol in ewes under summer climatic conditions. Ewes were synchronized for estrus using the OvSynch protocol and a dose of LC (20 mg/kg body weight) was intravenously (IV) administered on the same day of PGF2α injection to one group (n = 8; LC group), while other ewes (n = 8; control group) received the same protocol without LC. Ultrasonographic evaluation (including B-mode, color, and pulsed Doppler) was used to assess the morphometrical and hemodynamic parameters of ovarian structures [number, size, and blood flow of follicles (GFs) and corpora lutea (CLs)] and uterus during the estrous phase (Day 0), and on Day 8 post ovulation (luteal phase). Uterine artery blood flow (MUA) was assessed by measuring the resistive index (RI) and pulsatility index (PI) at both stages. The serum samples were collected to measure the concentrations of estradiol (E2), progesterone (P4), and total antioxidant capacity (TAC) using commercial kits. Results revealed a significant (P<0.05) increase in the colored pixel area of GFs and uterus in the LC group (392.84 ± 31.86 and 712.50 ± 46.88, respectively) compared to the control one (226.25 ± 17.74 and 322 ± 18.78, respectively) during Day 0. Circulating E2 and TAC levels were significantly (P<0.05) higher in the LC-treated ewes (31.45 ± 1.53 pg/ml and 1.80 ± 0.13 mM/L, respectively) compared to those in the control ewes (21.20 ± 1.30 pg/ml and 0.98 ± 0.09 mM/L, respectively) during Day 0. Moreover, LC improved the colored pixel area of CLs (2038.14 ± 102.94 versus 1098 ± 82.39) and uterus (256.38 ± 39.28 versus 121.75 ± 11.36) and circulating P4 (2.99 ± 0.26 ng/ml versus1.67 ± 0.15 ng/ml) on Day 8. Values of RI of MUA were significantly lower in the LC group compared to the control one on Day 0 and Day 8 (0.48 ± 0.03 versus 0.72 ± 0.03 and 0.58 ± 0.03 versus 0.78 ± 0.02, respectively). In conclusion, LC incorporation in the OvSynch protocol enhanced the morphometrical and hemodynamic parameters of the ovarian structures and the uterus concomitantly with improvements in the TAC, E2, and P4 concentrations in ewes under hot summer conditions.

Peculiarities of clinical signs, course and treatment of musculoskeletal system lesions in post-COVID syndrome.

Post-COVID syndrome (PCS) is a frequent phenomenon of patients who have suffered from an acute attack of COVID-19 infection, and it is characterized by a wide range of symptoms from different organs and systems including the musculoskeletal system (MSS). However, peculiarities of MSS lesions have not been sufficiently studied to date, in particular, in the aspect of the therapeutic process. We aimed to investigate peculiarities of MSS lesions in patients with PCS. Observations were carried out in 142 patients with PCS and MSS lesions. The age of patients was 36-67 years. Up-to-date methods of disease verification were used. An acute period of COVID-19 in all the patients was of moderate severity without oxygen support. Musculoskeletal system lesions in patients with PCS were found to appear 1-4 weeks after the experienced acute period of COVID-19 infection. Against the background of significant arthralgia (100%) in 93 (65.5%) patients manifestations of acute arthritis were detected, the frequency of which increased with age. Musculoskeletal system lesions were found against the background of dominating PCS manifestations from the cardiovascular and digestive systems. Deterioration of the course and results of treatment of diseases caused by an age-related polymorbid background was determined. Certain difficulties in the treatment of MSS lesions by means of non-steroidal anti-inflammatory drugs and limitation in the use of glucocorticosteroids are caused by severe gastroduodenopathy and arterial hypertension. Long-term, up to 6 months, administration of L-arginine, L-carnitine and quercetin in the rehabilitation complex improved the overall results of treatment of PCS manifestations including arthropathy. Musculoskeletal system lesions in patients with PCS are not the main constituent of this syndrome. Difficulties in the treatment of arthropathy are due to the signs of gastroduodenopathy and arterial hypertension. Additional administration of L-arginine, L-carnitine and quercetin is reasonable.

Comparative analysis of body weight gain in laboratory animals with different routes of administration of Lcarnitine

In recent years, several studies have been published that suggest that L-carnitine supplementation may affect weight in some animal species and humans, and may also affect the body composition of growing animals. Currently, only a few results are available on the effects of L-carnitine on weight loss and body composition in animals. Therefore, the purpose of this study was to find out whether injections of L-carnitine can influence the dynamics of the weight of laboratory animals. Toxicity studies were conducted on outbred rats in October 2021 in the vivarium of the St. Petersburg State University of Veterinary Medicine. The study involved females weighing 190-210 grams, purchased from the Federal State Unitary Enterprise “Nursery of Laboratory Animals “RAPPOLOVO”. When studying subchronic toxicity after subcutaneous and intramuscular administration, L-carnitine was administered at 2 dose levels. Doses were determined based on the results of the acute toxicity experiment: 1/5 and 1/10 of the maximum tolerated dose. The first experimental group (n=10) received the drug intramuscularly at a dose of 0.08 mg/kg (1/5 of 2000 mg/kg). The second experimental group (n=10) received the drug intramuscularly at a dose of 0.04 mg/kg (1/10 of 2000 mg/kg). The third experimental group received subcutaneous L -carnitine at a dose of 0.08 mg/kg (1/5 of 2000 mg/kg), the fourth experimental group received subcutaneous L-carnitine at a dose of 1/10 of the maximum tolerated (2000 mg/kg body weight). Group 5 was the control group (n=10) and received sodium chloride 0.09% intramuscularly at a dose of 1/5 of 2000 mg/kg, group 6 was the control group and received sodium chloride 0.09% subcutaneously at a dose of 1/5 of 2000 mg /kg. As a result of studies of subchronic toxicity on laboratory animals of the drug L-carnitine for veterinary use with subcutaneous and intramuscular administration, it was established that a dosage of 1/5 of the maximum tolerated, and a dosage of 1/10 of the maximum tolerated, does not cause changes in the dynamics of body weight animals.

#4655 IMPACT OF MAGNESIUM ASPARTATE AND L-CARNITINE ON INFLAMMATION, INSULIN RESISTANCE AND ATHEROSCLEROSIS PROGRESSION IN DIABETIC HEMODIALYSIS PATIENTS

Abstract Background and Aims The development of new pathogenetic treatment programs to reduce cardiovascular risk in diabetic patients with end-stage kidney disease is an important task of modern nephrology. In these conditions, considering the essential role of magnesium and L-carnitine deficiency in the mechanisms (via endothelial and metabolic disorders) of cardiovascular diseases, we evaluated the effect of the combined use of magnesium aspartate and L-carnitine on inflammation, insulin resistance and the atherosclerosis progression of carotid arteries in type 2 diabetic hemodialysis (HD) patients. Method 42 type 2 diabetic HD patients were included in this prospective cohort study (male, 26; age, 59.5 ± 0.7 years; HD duration, 31.2 ± 4.6 month; diabetes mellitus duration, 174.6 ± 7.8 month). Depending on the treatment programme, patients were divided into two groups: the 1st (main) group (n = 22) in addition to basic treatment (hypoglycemic, antihypertensive therapy, correction of anemia, hyperparathyroidism, hyperphosphatemia) was treated by combination of magnesium aspartate (0.5 g/day orally) and L-carnitine (1 g/day parenterally after each HD session (three times weekly); the 2nd (comparison) group (n = 20) was only on the standard therapy. Complex treatment lasted 12-months; administration of L-carnitine was performed continuously throughout the year, while magnesium aspartate – by three 2-months’ courses per year. Serum content of tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP) and fibrinogen as inflammatory biomarkers were determined. The homoeostasis model of assessment-insulin resistance (HOMA-IR) as an index of insulin resistance was estimated. Common carotid artery intima-media thickness (CСА IMT) as an index of the atherosclerosis severity was measured by ultrasound. Data are expressed as means ± SEM. Wilcoxon T-test was used for comparison of the dependent variables, Mann-Whitney U-test – for independent ones. Results In diabetic HD patients undergoing complex treatment with a combination of magnesium aspartate and L-carnitine after 12 months of observation CCA IMT did not change (0.88 ± 0.05 vs. 0.88 ± 0.05 mm; Z = 0.09, p = 0.925), while a significant increase (by 9.1%) in the CCA IMT was determined in subjects, who were on basic therapy (0.98 ± 0.04 vs. 1.07 ± 0.04 mm; Z = 2.27, p = 0.023). In addition, after 12 months of treatment, the indicated index between 1st and 2nd groups differed (p = 0.006). By the end of follow-up, the TNF-α, CRP and fibrinogen contents in patients who were on modified therapy were 44.7, 56.4 and 78.2% from baseline, a similar indices in patients receiving standard treatment – 70.7, 77.3 and 88.8% respectively, and after one year the main group and the comparison group on the serum concentrations of TNF-α (p = 0.089), CRP (p = 0.030) and fibrinogen (p = 0.026) differed. Magnesium aspartate and L-carnitine supplementation significantly improve HOMA-IR, and after 12 months of observation, the indicated index in the 2nd group exceeded (p = 0.003) that in the 1st one (Table 1). Conclusion (1) The combined use of magnesium aspartate and L-carnitine, in addition to the basic 12-month treatment, prevents the atherosclerosis progression of CCA, provides an effective reduction of the activity of chronic inflammation, improves insulin resistance in type 2 diabetic HD patients. (2) Long-term modified treatment may reduce the cardiovascular risk in these subjects.

Protective Effects of L-carnitine and Co-enzyme Q10 Against Oxidative Stress Damage in Hypertension

In this study, it was aimed to investigate the effects of L-carnitine and Co-enzyme Q10 administration together with ACE Inhibitor (ACE inh.) on oxidative stress parameters in liver, brain and kidney tissues in L-NAME hypertensive rats. At the study, divided all rats into eight groups, four groups with 14 days of experiment time and four groups with 28 days of experiment time. At the end of the experiment, the rats were euthanized and their liver, brain and kidney tissues were taken. Malondialdehyde (MDA), glutathione (GSH) and nitric oxide (NO) activities were measured in tissue supernatants. While NO and MDA levels increased in all tissues, a significant decrease was observed in GSH levels (P&amp;lt;0.001). In conclusion, it is suggested that supplementation of L-carnitine and CoQ10 can be considered as a combination therapy strategy for patients prone to higher levels of oxidative stress and inflammation.

Protective Effects of L-carnitine and Co-enzyme Q10 Against Oxidative Stress Damage in Hypertension

In this study, it was aimed to investigate the effects of L-carnitine and Co-enzyme Q10 administration together with ACE Inhibitor (ACE inh.) on oxidative stress parameters in liver, brain and kidney tissues in L-NAME hypertensive rats. At the study, divided all rats into eight groups, four groups with 14 days of experiment time and four groups with 28 days of experiment time. At the end of the experiment, the rats were euthanized and their liver, brain and kidney tissues were taken. Malondialdehyde (MDA), glutathione (GSH) and nitric oxide (NO) activities were measured in tissue supernatants. While NO and MDA levels increased in all tissues, a significant decrease was observed in GSH levels (P

Concomitant Administration of L-carnitine and Performing High-Intensity Interval Training Effects on the Genes Involved in Mitochondrial Fusion and Apoptosis in Rat Liver

Concomitant Administration of L-carnitine and Performing High-Intensity Interval Training Effects on the Genes Involved in Mitochondrial Fusion and Apoptosis in Rat Liver

Effects of Dietary Supplementation of L-Carnitine and Mannan-Oligosaccharides on Growth Performance, Selected Carcass Traits, Content of Basic and Mineral Components in Liver and Muscle Tissues, and Bone Quality in Turkeys

The study aimed to determine the effect of L-carnitine and Bio-Mos administration on selected production performance, slaughter parameters, elemental and mineral content of liver, breast and thigh muscles, and physical, morphometric, strength and bone mineral composition parameters of turkeys. The experiment was conducted on 360 six-week-old Big-6 turkey females, randomly divided into three groups of 120 birds each (six replicates of 20 birds). The turkeys of the control group were fed standard feed without additives; group II was fed with drinking water, a preparation containing L-carnitine at a dose of 0.83 mL/L, while group III was provided mixed feed with 0.5% Bio-Mos. The addition of L-carnitine and Bio-Mos increased body weight at 16 weeks (p = 0.047) and reduced the proportion of fat in the breast muscle (p = 0.029) and liver (p = 0.027). It also modified the content of some minerals in breast muscle, thigh muscle, liver, and bone. Furthermore, the addition of L-carnitine and Bio-Mos increased bone mass and length and modified the value of selected morphometric and strength parameters. The results indicate a positive effect of the applied feed additives on selected rearing indices and carcass quality while improving the elasticity and fracture toughness of the femur. There is a need for further research to determine optimal doses of L-carnitine and Bio-Mos in poultry nutrition.

Effects of Various Lipid Sources and L-Carnitine Supplementation on the Growth Performance, Body Composition, and Antioxidants Enzyme Ability of Dog Conch Larvae, Laevistrombus canarium

A feeding experiment was conducted to study the effects of dietary lipid sources and L-carnitine on the growth performance, body component, muscle fatty acid composition, and antioxidant enzyme ability of average weight of 0.28 g dog conch larvae, Laevistrombus canarium. Three sources of lipid: fish oil, soybean oil, and beef tallow were tested in combination with two levels (0 and 0.5%) of L-carnitine. The dog conch larvae fed diets containing fish oil with L-carnitine supplementation exhibited the highest weight gain. After air exposure challenge, the liver tissue of dog conch fed the diets containing soybean oil and beef tallow without supplemented L-carnitine had lower levels of superoxide dismutase (SOD, U min−1), phenoloxidase (PO, U min−1), and glutathione peroxidase (GPx, mU/mL) activity. The activity of SOD, PO, and GPx of dog conch larvae increased with increasing levels of dietary L-carnitine. In particular, dog conch larvae fed the diet containing fish oil supplemented with L-carnitine exhibited significantly ( P &lt; 0.05 ) enhanced antioxidant responses. The thiobarbituric acid reactive substances (TBARS) in the muscle tissue of dog conch larvae fed the diet containing fish oil without L-carnitine supplementation showed significantly ( P &lt; 0.05 ) higher activity. It was concluded that dietary administration of L-carnitine can enhance resistance against beta-oxidation, and the administration of fish oil in the diet was the best strategy to promote growth due to high nutritional availability.

Therapeutic effects of L-arginine, L-carnitine, and mesenchymal stem cell-conditioned medium on endometriosis-induced oocyte poor quality in an experimental mouse model.

The present study aimed to explore the potential ameliorative effects of L-arginine (LA), L-carnitine (LC), and bone marrow mesenchymal stem cell-conditioned medium (BMSC-CM) on endometriosis (EMS) model in vivo and in vitro. The animals were divided into two main groups, normal and EMS-induced mice. Normal and EMS-induced groups were injected with or without LA (250 mg/kg), LC (250 mg/kg), and BMSC-CM (a final volume of 100 μL of CM/mouse). At the end of the study, the level of total antioxidant capacity (TAC), nitric oxide (NO), and total oxidative status (TOS) were measured in plasma. Furthermore, immature oocytes were collected from two groups and cultured in a maturation medium. Subsequently, the rates of in vitro maturation, in vitro fertilization (IVF), and in vitro embryonic development were evaluated. The results revealed that administration of LA, LC, and BMSC-CM ameliorated the oxidative status through maintaining TAC and alleviating TOS and NO levels. More importantly, the maturation and fertilization rates, blastocyst development, and total blastocyst cell numbers significantly increased in LA, LC, and BMSC-CM-administrated groups compared to the control group. In both the normal and EMS groups, the highest IVF, cleavage, and blastocyst percentages were associated with BMSC-CM treatment (p < 0.05). Altogether, LA, LC, and BMSC-CM have therapeutic effects on impaired oocyte quality and promote subsequent development in vitro, probably through normalization of nitro-oxidative stress, thus offering potential alternatives to conventional therapies during assisted reproductive technologies for patients with EMS-associated sub/infertility.

Dietary administration of l-carnitine during the fattening period of early feed restricted lambs modifies lipid metabolism and meat quality

Early feed restriction of lambs promotes a permanent mitochondrial dysfunction that impairs β-oxidation of fatty acids along the whole life. Therefore, dietary l-carnitine might help to improve the mitochondrial function of these lambs, thus modifying lipid metabolism and meat quality traits. In order to test this hypothesis an experiment was carried out with 22 Merino lambs that were subjected to an early feed restriction during the suckling period. Once weaned, the lambs were allocated to a control group (CTRL, n = 11) being fed ad libitum a complete pelleted diet during the fattening phase, whereas the second group (CARN, n = 11) received the same diet formulated with 3 g/kg of l-carnitine. Carcass characteristics were not affected (P > 0.05) by treatment. However, lambs fed l-carnitine showed higher amounts of intramuscular fat (26.5 vs. 33.6 g/kg fresh matter; P = 0.047) with a lower ratio between polyunsaturated and saturated fatty acids (0.425 vs 0.333; P = 0.023) and a higher atherogenic (0.507 vs 0.597; P < 0.001) and thrombogenic index (1.23 vs 1.42; P < 0.001). An increase in lightness (P < 0.05) and a tendency to improved oxidative stability in cooked meat (P = 0.066) were also observed in the CARN group. Consequently, dietary l-carnitine supplied during the fattening period of early feed restricted lambs modifies meat quality traits thus increasing lightness, oxidative stability and intramuscular fat content, but worsening the fatty acid profile.

Effects of l-carnitine Administration on Sperm and Sex Hormone Levels in a Male Wistar Rat Reproductive System Injury Model in a High-Altitude Hypobaric Hypoxic Environment

The plateau environment impacts male reproductive function, causing decreased sperm quality and testosterone levels. l-carnitine can improve the semen microenvironment. However, the role of l-carnitine in a high-altitude environment remains unclear. In our study, we investigated the effects of l-carnitine administration in a male Wistar rat reproductive system injury model in the context of a simulated high-altitude environment. Rats were randomly divided into a normal control group (group A1, A2-low dose and A3-high dose) and high-altitude model groups (group B, C-low dose and D-high dose) with 20 rats in each group. With the exception of the normal control group exposed to normoxic conditions, the other groups were maintained in a hypobaric oxygen chamber that simulated an altitude of 6000 m for 28 days. In the experimental period, the low-dose groups (A2 and C) were administered 50 mg/kg l-carnitine via intraperitoneal injection once a day, and the high-dose groups (A3 and D) were given 100 mg/kg. After the feeding period, blood samples were collected to assess blood gas, serum hormone levels and oxidative stress. Sperm from the epididymis were collected to analyse various sperm parameters. After obtaining the testicular tissue, the morphological and pathological changes were observed under a light microscope and transmission electron microscopy (TEM). The impact of the simulated high-altitude environment on the rat testis tissue is obvious. Specifically, a decreased testicular organ index and altered indices of arterial blood gas and serum sex hormone levels caused testicular tissue morphological damage, reduced sperm quality, increased sperm deformity rate and altered malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) concentrations. The results demonstrate that l-carnitine can be administered as a preventive intervention to reduce the reproductive damage caused by high-altitude hypobaric and hypoxic environments and improve semen quality in a rat model.

PS-B08-7: L-CARNITINE AMELIORATES DIABETIC KIDNEY DISEASE BY ALLEVIATING MITOCHONDRIAL ABNORMALITY IN SDT-FATTY RATS

Background and Aims: Abnormal fatty acid metabolism is associated with the progression of diabetic kidney disease (DKD). Carnitine plays a central role in β;-oxidation and energy production by transporting long-chain fatty acids from the cytoplasm to the mitochondria. Recently, we found that significant ectopic fat was accumulated in the kidney tissue in DKD patients compared with those in minimal change kidney disease patients. Juvenile visceral steatosis (jvs) mice, described as an animal model for systemic carnitine deficiency, introduce a marked ectopic fat accumulation in the kidney. These findings suggest that abnormal carnitine dynamics in DKD cause ectopic fat accumulation due to abnormality of the fatty acid metabolism. However, the association between abnormalities of carnitine metabolism and the progression of DKD is unknown. Method: Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model was used. Unilateral nephrectomy was performed and 0.3% salt water was administered at 6 weeks of age, and created a renal dysfunction model in SDT fatty rat (DKD model). Age-matched male Sprague-Dawley (SD) rat was used as a control. Experiment 1: We compared 3 groups; SD rats (n = 8), SDT fatty rats (n = 8), DKD rats (n = 8). Experiment 2: We compared 3 groups; SD rats with sham operation (n = 8), DKD rats (n = 7), DKD rats treated with L-carnitine administration (0.75% L-carnitine diet) for 10 weeks (n = 6). All rats were sacrificed at 17 weeks old. Carnitine was measured by the enzyme cycling method. Acylcarnitine was analyzed by the tandem-mass spectrometry. Results: Plasma and renal free carnitine levels and short/middle-long chain acylcarnitine ratio were significantly decreased in DKD rats compared with those in SD and SDT fatty rats. The renal expression levels of organic cation / carnitine transporter 2 (OCTN2), carnitine palmitoyl transferase 1a (CPT1a), CPT2 and carnitine acetyltransferase (CrAT) were significantly decreased in DKD rats compared with those in SD and SDT fatty rats. Similarly, peroxisome proliferator-activated receptor γ co-activator 1α (PGC1α) activity was decreased in DKD rats. L-carnitine administration significantly improved renal function, urinary albumin excretion, interstitial fibrosis and renal ectopic fat accumulation in DKD model rats. L-carnitine administration ameliorated the decrease of renal OCTN2, CPT1a, CPT2 and CrAT protein expression, and significantly improved PGC1α activity in DKD model rats. Furthermore, L-carnitine administration mitigated lipid peroxidation and mitochondrial dysfunction in DKD rats. Conclusion: L-carnitine administration might be a promising therapeutic strategy for improving renal function by alleviating mitochondrial dysfunction in DKD rat model.

Protective Effect of L-carnitine against Cefquinome Sulfate Induced Testicular Damage and Oxidative Stress in Male Albino Rats

The present study was conducted to evaluate the protective effect of L-carnitine (LC) against possible deleterious effects of cefquinome sulfate (CS) on antioxidant capacity, fertility parameters and histopathological findings of reproductive organs in male rats. Therefore, seventy two mature male rats were equally divided into four equal groups as following: The control group of rats was administered two s.c. doses of physiological saline (vehicle of other drugs) (2ml/kg b.wt. once daily for 5 successive days and 2ml/kg b.wt. once daily for 8 successive weeks), the second group was s.c. administered LC (200 mg/kg b.wt. once daily for 8 successive weeks), the third group was s.c. administered CS (50 mg/kg b.wt. once daily for 5 successive days) and the fourth group was s.c. administered CS concomitantly with LC by the same doses. The obtained results showed that administration of CS induced a significant (P≤ 0.05) increase in serum level of Malondialdehyde (MDA) and total sperm abnormalities with significant (P≤ 0.05) decrease in serum level of total antioxidant capacity (TAC), sperm motility and total sperm count. Moreover, CS induced histopathological changes in tissues of testes and epididymis. Conversely, administration of LC concomitantly with CS ameliorates all the previous antioxidant, fertility and histopathological alterations induced by CS. It could be concluded that CS induced some undesired effects on antioxidant activity, fertility parameters and histopathological findings which could be ameliorated by LC in male albino rats.