Carnitine Group Research Articles

Renal Protective Effects of L-Carnitine on Lead-Induced Nephropathy in Wistar Rats

Background: Lead is a heavy metal used in industries in developing countries. Lead exposure remains a widespread problem. Lead may induce molecular damage in the kidney as a consequence of Reactive Oxygen Species (ROS) formation, induction of caspase-3, and apoptosis.Methods: Thirty male Wistar rats (Mean±SD weight: 300±20 g) were randomly divided into 3 equal groups: control (normal saline, oral), lead group (lead 100 mg/kg/d, oral) and lead+L-Carnitine (lead 100 mg/kg+L-Carnitine 200 mg/kg, intraperitoneal injection) for one week. At the end of the experiment, plasma creatine kinase activity, plasma creatinine and urea concentrations and plasma Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx), catalase and nitric oxide levels were determined. Glutathione and malondialdehyde levels in renal tissue were also measured.Results: Creatine kinase, creatinine and urea levels increased significantly, in the group treated with lead (P<0.05), compared to the control group. Administration of L-Carnitine in (Lead+carnitine treated group) significantly (P<0.05) decreased creatine kinase activity and plasma urea and creatinine contents. Enzymatic activity (SOD, GPx, and CAT) decreased significantly in the lead group, in comparison with the control group (P<0.05). Treatment with L-Carnitine significantly retrieved the depletion in enzyme activity (P<0.05). However, there were no significant differences in the GPx parameter between the Lead+carnitine group, in comparison with the control group.Conclusion: L-Carnitine administration in rats with lead-induced nephropathy led to improved kidney protection, due to the reduction of Lipid Peroxidation (LPO). Furthermore, L-Carnitine prevents the adverse effects of Reactive Oxygen Species (ROS), which is an important biomolecules mechanism.

Effect of early supplementation of exogenous carnitine on liver mitochondrial damage in severely scalded rats and its pathological mechanism

Objective: To observe the effect of early supplementation of exogenous carnitine on liver mitochondrial damage in severely scalded rats and to explore its pathological mechanism. Methods: Seventy-two adult female Sprague-Dawley rats were divided into sham injury group, scald injury group, and scald injury+ carnitine group according to the random number table, with 24 rats in each group. Rats in sham injury group was sham injured on the back by immersing in 37 ℃ water bath for 12 s without fluid replacement. While rats in scald injury and scald injury+ carnitine groups were inflicted with 30% total body surface area (TBSA) full-thickness scald on the back by immersing in 98 ℃water bath for 12 s. Immediately after injury, rats in scald injury group and scald injury+ carnitine group were injected with Ringer's lactate solution with the dosage of 4 mL·kg(-1)·%TBSA(-1) via tail vein according to the Parkland formula, meanwhile rats in scald injury+ carnitine group were injected with L-carnitine solution with dosage of 300 mg·kg(-1)·d(-1) via tail vein from post injury hour (PIH) 1. At PIH 12, 24, 48 and 72, abdominal aorta blood and liver tissue were collected from 6 rats in each group. The serum levels of carnitine, β-hydroxybutyric acid, and ornithine carbamoyltransferase (OCT) were determined with enzyme-linked immuno sorbent assay, and the serum levels of lactate dehydrogenase (LDH), alanine aminotransferase(ALT), and aspartate transaminase (AST) was determined by automatic biochemical analyzer, Pathological changes of rats liver tissue were detected with HE staining. Data were processed with analysis of variance of factorial design and Student-Newman-Keulstest or Tamhane test, Bonferroni correction. Results: (1) Compared with sham injury group, the serum level of carnitine of rats in scald injury group was significantly lower at each time point (P 0.05]. The serum level of carnitine in scald injury+ carnitine group was significantly higher than that in scald injury group at each time point (P 0.05). The serum levels of LDH of rats in scald injury+ carnitine group were significantly lower than those of scald injury group at each time point (P 0.05). The serum levels of ALT and AST in scald injury+ carnitine group both showed a trend of decrease, and they peaked at PIH 12 [(260±25), (1 511±145) U/L, respectively]. (6) The liver tissue of rats in sham injury group was basically normal at each time point. The degree of liver injury of rats in scald injury+ carnitine group was lighter than that in scald injury group. The liver tissue of rats in scald injury group at PIH 72 showed obvious cytoplasm loose, liver tissue structure loss with diffuse fatty degeneration and large coagulative necrosis. Only partially scattered fatty degeneration was observed in the liver tissue of ras in scald injury+ carnitine group. Conclusions: By early supplementation of exogenous carnitine, serum levels of carnitine and β-hydroxybutyric acid can be restored to normal levels faster, alleviate mitochondrial damage of hepatocytes, and maintain the metabolic stability of hepatocytes in early stage of severe scald.

L-carnitine counteracts prepubertal exposure to cisplatin induced impaired sperm in adult rats by preventing germ cell apoptosis

ABSTRACTWe investigated the possible protective effects of L-carnitine on cisplatin induced prepubertal gonadotoxicity and on adult sperm. Prepubertal 30-day-old male rats were divided randomly into three groups: control (n = 12), cisplatin exposed (n = 16) and carnitine treated after cisplatin exposure (n = 16). Rats in the experimental groups were injected with a single dose of cisplatin. L-carnitine was injected 1 h before cisplatin administration and for the following 3 days for the cisplatin + carnitine group. The rats were sacrificed at 31 or 90 days old and their testes were harvested for morphometric and histopathological analysis. Testes of 31-day-old prepubertal rats were examined for germ cell apoptosis using the TUNEL method and for proliferation using PCNA immunostaining. The morphology, motility, quantity and vitality of sperm in epididymal fluid samples of adult 90-day-old rats also were evaluated. L-carnitine treatment reduced testicular damage and the number of TUNEL positive cells significantly, while the number of PCNA positive cells in the cisplatin + carnitine group increased compared to the cisplatin group. During the adult period, epididymal sperm count and viability were improved in rats treated with L-carnitine before prepubertal cisplatin injection. L-carnitine may reduce late testicular and spermatic damage caused by cisplatin administration to prepubertal rats by inducing germ cell proliferation and preventing apoptosis.

Randomized Trial of Carnitine for the Prevention of Perioperative Atrial Fibrillation

Atrial fibrillation (AF) is one of the most common complications in patients who undergo coronary artery bypass graft surgery (CABG). The aim of this study was to evaluate the effect of L-carnitine administration on postoperative AF and the levels of C-reactive protein (CRP) following CABG. The effects of L-carnitine on the incidence of acute kidney injury after CABG were also assessed. One hundred thirty-four patients undergoing elective CABG, without a history of AF or previous L-carnitine treatment, were randomly assigned to an L-carnitine group (3000 mg/d L-carnitine) or a control group. CRP levels, as a biomarker of inflammation, were assessed in all the patients before surgery as baseline levels and 48 hours postoperatively. Neutrophil gelatinase-associated lipocalin, as a kidney biomarker, was also measured in the patients before surgery and 2 hours thereafter. The incidence of AF was 13.4% in our population. The incidence of AF was decreased in the L-carnitine group (7.5% in the L-carnitine group vs 19.4% in the control group; P = 0.043) and the postoperative CRP level (8.79 ± 6.9 in the L-carnitine group, and 10.83 ± 5.7 in the control group; P = 0.021). The postoperative neutrophil gelatinase-associated lipocalin concentration demonstrated no significant rise after surgery compared with the preoperative concentration (72.54 ± 20.30 in the L-carnitine group vs 67.68 ± 22.71 in the placebo group; P = 0.19). Our study showed that L-carnitine administration before CABG might inhibit and reduce the incidence of AF after CABG. It seems that a rise in the CRP level, as an inflammation marker, may be associated with the incidence of AF. Inflammation as measured by CRP was also reduced in the carnitine group, compared with the control group.

Protective role of CoQ10 or L-carnitine on the integrity of the myocardium in doxorubicin induced toxicity.

Doxorubicin (DOX) is a chemotherapeutic agent used for treatment of different cancers and its clinical usage is hindered by the oxidative injury-related cardiotoxicity. This work aims to declare if the harmful effects of DOX on heart can be alleviated with the use of Coenzyme Q10 (CoQ10) or L-carnitine. The study was performed on seventy two female Wistar albino rats divided into six groups, 12 animals each: Control group; DOX group (10mg/kg); CoQ10 group (200mg/kg); L-carnitine group (100mg/kg); DOX+CoQ10 group; DOX+L-carnitine group. CoQ10 and L-carnitine treatment orally started 5days before a single dose of 10mg/kg DOX that injected intraperitoneally (IP) then the treatment continued for 10days. At the end of the study, serum biochemical parameters of cardiac damage, oxidative stress indices, and histopathological changes were investigated. CoQ10 or L-carnitine showed a noticeable effects in improving cardiac functions evidenced reducing serum enzymes as serum interleukin-1 beta (IL-1 β), tumor necrosis factor alpha (TNF-α), leptin, lactate dehydrogenase (LDH), Cardiotrophin-1, Troponin-I and Troponin-T. Also, alleviate oxidative stress, decrease of cardiac Malondialdehyde (MDA), Nitric oxide (NO) and restoring cardiac reduced glutathione levels to normal levels. Both corrected the cardiac alterations histologically and ultrastructurally. With a visible improvements in α-SMA, vimentin and eNOS immunohistochemical markers. CoQ10 or L-carnitine supplementation improves the functional and structural integrity of the myocardium.

Effect of L-Carnitine Supplementation on Reverse Remodeling in Patients with Ischemic Heart Disease Undergoing Coronary Artery Bypass Grafting: A Randomized, Placebo-Controlled Trial

During cardiac failure, cardiomyocytes have difficulty in using the substrates to produce energy. <smlcap>L</smlcap>-carnitine is a necessary nutrient for the transport of fatty acids that are required for generating energy. Coronary artery graft surgery reduces the plasma levels of <smlcap>L</smlcap>-carnitine and increases the oxidative stress. This study demonstrates the effect of <smlcap>L</smlcap>-carnitine supplementation on the reverse remodeling of patients undergoing coronary artery bypass graft. Patients with ischemic heart failure who underwent coronary graft surgery were randomized to group A - supplemented with <smlcap>L</smlcap>-carnitine or group B controls. Left ventricular ejection fraction, left ventricular systolic and diastolic diameters were assessed preoperatively, 60 and 180 days after surgery. Our study included 28 patients (26 [93.0%] males) with a mean age ± SD of 58.1 ± 10.5 years. The parameters for the evaluation of reverse remodeling did not improve after 60 and 180 days of coronary artery bypass grafting in comparison between groups (p > 0.05). Evaluation within the <smlcap>L</smlcap>-carnitine group showed a 37.1% increase in left ventricle ejection fraction (p = 0.002) and 14.3% (p = 0.006) and 3.3% (p > 0.05) reduction in systolic and diastolic diameters, respectively. <smlcap>L</smlcap>-carnitine supplementation at a dose of 50 mg/kg combined with artery bypass surgery did not demonstrate any additional benefit in reverse remodeling. However, evaluation within the <smlcap>L</smlcap>-carnitine group may indicate a clinical benefit of <smlcap>L</smlcap>-carnitine supplementation.

Effects of supplementation of medium with different antioxidants during in vitro maturation of bovine oocytes on subsequent embryo production.

The aim of this study was to assess the effects of different antioxidants on the levels of reactive oxygen species (ROS) and glutathione (GSH) in oocytes during in vitro maturation (IVM), as well as on the production of embryos. Oocyte of slaughterhouse-derived cattle ovaries were placed in IVM with different antioxidants: quercetin (2μM), cysteamine (100μM), carnitine (0.5mg/ml), vitamin C (50μg/ml) or resveratrol (2μM). Oocytes matured without any antioxidant supplementation were used as control. The oocytes were assessed for maturation rates and for ROS and GSH levels by fluorescence staining in 2',7'-dichlorodihydrofluorescein diacetate and Cell Tracker Blue, respectively. Embryo production was assessed in terms of cleavage, blastocysts and hatching rates and embryo cell numbers. The results expressed in arbitrary fluorescence units showed ROS reduction (p<.05) in the groups with quercetin (27.5±3.4), vitamin C (27.1±3.0) or resveratrol (28.1±4.7), in comparison with those with cysteamine (34.9±4.5), carnitine (34.6±3.8) or to the control group (36.5±5.2). GSH levels increased (p<.05) in cysteamine (63.5±5.5) or carnitine (60.8±4.4) groups in comparison with quercetin (52.7±5.1), vitamin C (53.0±3.8), resveratrol (53.1±4.4) or to the control (49.6±4.5). Nuclear maturation cleavage and hatched blastocysts rates did not differ (p>.05) between groups. However, blastocyst rates after in vitro fertilization in quercetin (53.5±3.9%), vitamin C (52.1±3.1%) resveratrol (54.2±4.0%), cysteamine (52.4±2.7%) or carnitine (54.2±3.1%) groups were higher (p<.05) than in the control (47.2±2.7%). Total cell numbers in embryos from the vitamin C, resveratrol, cysteamine or carnitine groups were higher than in quercetin and control groups, which were similar to each other. The results suggest that using antioxidants during IVM may reduce oxidative stress either by decreasing ROS levels directly or by increasing GSH levels in oocytes, depending on the type of antioxidant used. Overall, oxidative stress control during IVM with the antioxidants examined here improved blastocyst development with similar efficacy.

Utilisation of supplemented l-carnitine for fuel efficiency, as an antioxidant, and for muscle recovery in Labrador retrievers.

The primary goal was to investigate the effects of l-carnitine on fuel efficiency, as an antioxidant, and for muscle recovery in Labrador retrievers. Dogs were split into two groups, with one group being supplemented with 250mg/d of Carniking™ l-carnitine powder. Two experiments (Expt 1 and Expt 2) were performed over a 2-year period which included running programmes, activity monitoring, body composition scans and evaluation of recovery using biomarkers. Each experiment differed slightly in dog number and design: fifty-six v. forty dogs; one endurance and two sprint runs per week v. two endurance runs; and differing blood collection time points. All dogs were fed a low-carnitine diet in which a fixed amount was offered based on maintaining the minimum starting weight. Results from Expt 1 found that the carnitine dogs produced approximately 4000 more activity points per km compared with the control group during sprint (P=0·052) and endurance runs (P=0·0001). Male carnitine dogs produced half the creatine phosphokinase (CPK) following exercise compared with male control dogs (P=0·05). Carnitine dogs had lower myoglobin at 6·69ng/ml following intensive exercise compared with controls at 24·02ng/ml (P=0·0295). Total antioxidant capacity (TAC) and thiobarbituric acid reactive substance (TBARS) results were not considered significant. In Expt 2, body composition scans indicated that the carnitine group gained more total tissue mass while controls lost tissue mass (P=0·0006) and also gained lean mass while the control group lost lean mass (P<0·0001). Carnitine dogs had lower CPK secretion at 23·06 v. control at 28·37mU/ml 24h after post-run (P=0·003). Myoglobin levels were lower in carnitine v. control dogs both 1h post-run (P=0·0157; 23·83 v. 37·91ng/ml) and 24h post-run (P=0·0189; 6·25 v.13·5ng/ml). TAC indicated more antioxidant activity in carnitine dogs at 0·16mm v. control at 0·13mm (P=0·0496). TBARS were also significantly lower in carnitine dogs both pre-run (P=0·0013; 15·36 v. 23·42µm) and 1h post-run (P=0·056; 16·45 v. 20·65µm). Supplementing l-carnitine in the form of Carniking™ had positive benefits in Labrador retrievers for activity intensity, body composition, muscle recovery and oxidative capacity.

EFFECTS OF L-CARNITINE SUPPLEMENTATION AT FORCED FEEDING PERIOD ON GROWTH PERFORMANCE AND PROXIMATE COMPOSITIONS OF BREAST MUSCLE AND LIVER OF MUSCOVY AND MOULARD DUCKS

An experiment was conducted using 300 ducks of day-old (180 Muscovy and 120 Moulard), based on sexing which was done for 500 ducklings at the first day of age where it was brought up in accordance with the principles of the French care for birds research and rearing of water fowls for fattening purposes until 12 weeks of age. At this age birds were divided within each breed according to feeding regime (forced feeding and ad libitum feeding group), and supplementation of L carnitine (1000 mg kg of diet) making eight groups until the end of the study (at 14 weeks). The results of the experiment revealed that, forced feeding has a significant increase in body weight and absolute or relative weight gain (5954.33 g, 1421.03 g and 23.51%, respectively) than ad libitum feeding (4506.75 g, 411.05 g and 8.94%; respectively). Under the regime of force-feeding Moulard ducks had significantly increased absolute and relative body weight gain (1808.16 g and 29.64%, respectively) than Muscovy ducks (930.67 g and 15.73% respectively). Feed conversion per kg increase in weight was the best in Moulard ducks than Muscovy under force-feeding regime (6.29 kg and 11.5 kg, respectively), and vice versa with the ad libitum feeding (18.89 for 11.06 kg, respectively), at the same time the Moulard ducks needed a larger amount of feed per kg liver, (in forced or ad libitum feeding) than Muscovy. El-Edel M.A. et al., 812 Force-feeding led to severe assembly of fat in the liver, which was significantly higher than in ad libitum feeding groups (57.78% from 35.28%, respectively) and on the contrary, was the percentage of protein (9.66% from 28.81%, respectively). Addition of L carnitine to the feed at forced feeding period resulted in a significant increase in the life weight (5731.97 g) than in non L carnitine fed group(5400.13 g), on the other hand other performance traits not affected significantly by the addition of L carnitine in feed. Liver weight (absolute and Percent) in L carnitine treatment group was higher than non L carnitine group in the ad libitum feeding group (it was not significant). Using L carnitine in ad libitum feeding groups achieved a higher percentage of dry matter in liver (30.88%) than those without L carnitine (28.98%), unlike the breast muscles; dry matter was higher in the group without L carnitine than with L carnitine (32.05% from 30.37%). It would be concluded from this study that using of Moulard duck is preferred for the foie gras production than Muscovy ducks because of its ability to receive large quantity of feed and has the highest feed conversion and a better feed per kg increase in weight as well as the absolute and relative weight of the liver from Muscovy ducks under the forced feeding regime. L carnitine supplementation has no effect on the foie gras production, but if it was added to the feed during the forced feeding period it improved live weight significantly.

Nephroprotective potential of carnitine against glycerol and contrast-induced kidney injury in rats through modulation of oxidative stress, proinflammatory cytokines, and apoptosis.

Contrast media (CM) are a major cause of nephropathy in high-risk patients. The aim of this study was to examine the effects of carnitine (CAR) in advanced nephrotoxicity due to CM administration in rats with glycerol-induced renal functional disorder. 40 rats were divided randomly into five groups (n = 8): (1) healthy group; (2) glycerol only (GLY); (3) glycerol and CM (GLY + CM); (4) glycerol, CM and 200 mg kg(-1) carnitine (CAR200, Carnitene(®); Sigma-tau/Santa Farma, Istanbul, Turkey); and (5) glycerol, CM and 400 mg kg(-1) carnitine (CAR400). Kidney injury was induced with a single-dose, intramuscular injection of 10 ml kg(-1) body weight (b.w.) of GLY. CAR was administered intraperitoneally. CM (8 ml kg(-1) b.w. iohexol, Omnipaque™; Opakim Medical Products, Istanbul, Turkey) was infused via the tail vein to the rats in Groups 3-5. l-carnitine administration significantly decreased serum creatinine and blood urea nitrogen levels. Superoxide dismutase and glutathione activity increased significantly in the treatment groups compared with the nephrotoxic groups. CAR400 significantly reduced malondialdehyde levels to healthy levels. In the treatment groups, tumour necrosis factor (TNF)-α, transforming growth factor 1β, interleukin 1β and caspase-3 gene expression decreased compared with the nephrotoxic groups. TNF-α and nuclear factor kappa-beta (NF-κB) protein expression increased after CM and CAR administration reduced both TNF-α and NF-κB expressions. Histopathologically, hyaline and haemorrhagic casts and necrosis in proximal tubules increased in the nephrotoxicity groups and decreased in the CAR groups. The results reveal that l-carnitine protects the oxidant/antioxidant balance and decreases proinflammatory cytokines and apoptosis in CM-induced nephrotoxicity in rats with underlying pathology. Depending on the underlying kidney pathologies, the incidence of CM-induced nephropathy (CIN) increases. Therefore, this is the best model to represent clinically observed CIN.

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.

Effects of intravenous l-carnitine on myocardial fatty acid imaging in hemodialysis patients: responders or non-responders to l-carnitine.

We investigated whether chronic intravenous administration of l-carnitine could improve myocardial fatty acid imaging in patients on maintenance hemodialysis. We enrolled 72 hemodialysis patients who had impaired myocardial fatty acid imaging and left ventricular dysfunction not based on coronary lesion. l-Carnitine (1,000 mg) was intravenously administered after dialysis for 1 year to 36 participants (Carnitine group), while not in the other 36 participants (Control group). Single-photon emission computed tomography (SPECT) using an iodinated fatty acid analogue, BMIPP, was performed. Uptake on SPECT images was graded in 17 segments on a five-point scale (0, normal; 4, absent) and assessed as BMIPP summed scores. During follow-up, 19 participants were discontinued from the study, and 53 participants (65 ± 12 years: 27 carnitine, 26 control) were analyzed. The mean BMIPP summed scores 1 year after carnitine administration did not differ from that before in the carnitine group, nor from that in the control group. However, improved SPECT (Changes in BMIPP summed scores <−20%) was found in 7 (25.9%) participants in the carnitine, whereas in 2 (7.7%) in the control group. Multivariate logistic analysis showed the improved SPECT was inversely associated with baseline serum albumin levels (1 g/L: odds ratio, 0.669); the cut-off was 35 g/L. Chronic intravenous l-carnitine might improve myocardial fatty acid imaging in a selected group of hemodialysis patients with hypoalbuminemia.

Impact of L-carnitine and Selenium Treatment on Testicular Apoptosis in Rats Exposed to 2.45 GHz Microwave Energy.

It has been suggested that electromagnetic radiation (EMR) by wireless devices (2.45 GHz) induces testicular apoptosis. We investigated if supplemental selenium (Se) and L-carnitine may reduce this adverse effect. Twelve-week old male Wistar albino rats were used in this study. Twenty-four rats were equally divided into four groups which were named as: sham group, EMR-only, EMR+L-carnitine (1.5 mg L-carnitine/kg/day) and EMR+Se (1.5 mg Se/kg/-every other day). The level of Bcl-2, Bax, caspase-3 and -8 were compared and a significant difference was found between the sham and EMR-only groups (p < 0.05), and Bcl-2, Bax, caspase-3 and -8 expressions increased in the EMR-only group. The level of Bcl-2, Bax, tumour necrosis factor-alpha (TNF-α), caspase-3 and -8 were compared and a significant difference was found between the sham and EMR+L-carnitine groups (p < 0.05) and Bcl-2, Bax, TNF-α, caspase-3 and -8 expressions increased in the EMR+L-carnitine group. The level of Bcl-2, Bax, TNF-α, caspase-3 and -8 were compared and a significant difference was found between the sham and EMR+Se groups (p < 0.05) and Bcl-2, Bax, TNF-α, caspase-3 and -8 expressions increased in the EMR+Se group. When the expression of caspase-8 was compared, a significant difference was found between the EMR-only and EMR+Se groups (p < 0.05). Caspase-8 expression decreased in EMR+Se group compared with EMR-only group. Electromagnetic radiation exposure resulted in testicular apoptosis in rats, mainly by the intrinsic pathways by down-regulated expression of caspase-8. Reduction in the activation of the intrinsic pathway of apoptosis was found higher with selenium administration compared with L-carnitine administration.

L-carnitine Increases Skeletal Muscle GLUT4 Expression and ImprovesMetabolic Control in Type 2 Diabetes

Background: L-carnitine is known to play a beneficial role in diabetes; however, there are no studies on the effect of L-carnitine on glucose transporter 4 (GLUT4) expression in high glucose condition. So the aim of this in vivo study was to investigate whether L-carnitine can improve insulin resistance in type 2 diabetes (T2DM) through increasing the expression of GLUT 4 in skeletal muscles. Methods: Thirty healthy male Sprague Dawely rats were randomly divided into: Control negative, control positive (Diabetic) and Carnitine groups. For induction of T2DM the control positive and carnitine groups' rats were fed high fat diet (HFD) for about 2 month, while control negative rats were fed on normal diet. Diabetic and carnitine groups received 35 mg/kg streptozocin (STZ) intraperitoneal. After confirming the development of T2DM in diabetic and carnitine groups L-carnitine was administered orally to the carnitine group in a dose of 3 gm carnitine / kg once daily for 4 weeks. At the end of treatment period, rats were sacrificed and blood samples were collected directly from the heart and the hindlimb soleus muscles were removed, snap- frozen and stored at−80◦C until analysis. Results: L-carnitine administration resulted in significant decrease (p<0:05) in serum glucose, serum insulin, and triglycerides: High Density Lipoprotein Cholesterol (TG:HDL) ratio of the carnitine group as compared to diabetic group. Carnitine administration showed also significant increase AMP-activated protein kinase (AMPK) activity and in total skeletal muscle GLUT-4 protein concentration. Conclusion: The results of this study demonstrate that carnitine supplementation ameliorates insulin resistance in type 2 diabetic rats and up-regulating GLUT4 protein expression in the skeletal muscles through increasing the activity of AMPK. So, carnitine administration may be a possible candidate for the treatment of T2DM.

Carnitine for prevention of antituberculosis drug‐induced hepatotoxicity: A randomized, clinical trial

In the present study, the potential benefits of oral carnitine in preventing antituberculosis drug-induced hepatotoxicity (ATDH) were evaluated. Fifty-four patients in the carnitine and 62 patients in the placebo group completed the study. The carnitine group received 1000 mg oral carnitine solution twice daily for 4 weeks. The placebo group received 10 mL of oral placebo solution twice daily for 4 weeks. ATDH was defined as an increase in the serum level of aspartate aminotransferase or alanine aminotransferase greater than three or five times of the upper limit of normal with or without clinical symptoms of hepatotoxicity, respectively. During the study period, 29 (25%) patients experienced ATDH. Among these patients, nine (16.7%) and 20 (32.3%) were in the carnitine and placebo groups, respectively (P = 0.049). Based on multivariate logistic regression model, age over 35 years old (odds ratio [OR] = 7.01, P = 0.002), human immunodeficiency virus infection (OR = 40.4, P < 0.001), diabetes mellitus (OR = 37.6, P = 0.001), and placebo treatment (OR = 0.1, P = 0.01) were identified as predisposing factors for ATDH. Results of our preliminary clinical trial suggested that cotreatment with 2000 mg oral L-carnitine solution daily for 4 weeks significantly decreased the rate of ATDH.

The Effects of Oral L-Carnitine Supplementation on Physical Capacity and Lipid Metabolism in Chronic Hemodialysis Patients

Background: It is well known that the physical activity in chronic hemodialysis patients decreases compared to that in normal subjects. In order to investigate the effects of <smlcap>L</smlcap>-carnitine on physical capacity and lipid metabolism, a cardiopulmonary exercise test using a bicycle ergometer was performed before and after 3 months of oral <smlcap>L</smlcap>-carnitine supplementation under double-blind conditions. Methods and Results: A total of 20 stable outpatients undergoing hemodialysis treatment were randomly divided into 2 groups: controls receiving placebo and patients receiving 900 mg <smlcap>L</smlcap>-carnitine p.o. daily. The levels of free and acyl carnitine increased significantly from 22.9 ± 7.3 to 149.9 ± 51.8 μmol/l and from 16.0 ± 2.8 to 100.3 ± 50.2 μmol/l, respectively, in the <smlcap>L</smlcap>-carnitine group; however, there was no significant change in other plasma lipid profiles. The exercise time was decreased and the heart rate at the anaerobic threshold was increased in the control group 3 months after the study period, but there were no such changes observed in the <smlcap>L</smlcap>-carnitine group. The minute ventilation/CO₂ output slope increased significantly from 38.9 ± 7.8 to 43.8 ± 11.8 in the <smlcap>L</smlcap>-carnitine group. It has been speculated that a shift in the energy source occurs from carbohydrate to lipid, in terms of an increase of oxygen demand. Conclusion:<smlcap>L</smlcap>-Carnitine supplementation might have some beneficial effects on the physical capacity of chronic hemodialysis patients due to the improvement of the lipid metabolism in the muscle.

The Effect of L-Carnitine on Oxidative Stress Responses of Experimental Contrast-Induced Nephropathy in Rats

ABSTRACTThis study was conducted to investigate the prophylactic effects of carnitine against contrast-induced nephropathy (CIN) and its relation to oxidant/antioxidant status in kidney, liver, heart, spleen and lung tissues in a CIN rat model. Twenty-eight adult male Wistar rats were divided into 4 groups, the control, contrast media (CM), carnitine and contrast media+carnitine (CM+carnitine) groups. Animals were placed in individual metabolism cages, and on the 2nd day, rats were deprived of water for 24 hr. On the 3rd day, contrast media were administered to groups CM and CM+carnitine. L-carnitine was administered on days 2, 3 and 4. Histopathological changes were evaluated in the right kidney after euthanization. Superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) and malondialdehyde (MDA) levels were measured in renal, liver, heart, spleen and lung tissues. The SOD activities in the renal (P<0.05), liver (P<0.001) and spleen (P<0.05) tissues were increased in the carnitine group. The CAT activities in the spleen tissue were decreased (P<0.01) only in the CM group. Renal (P<0.05), liver (P<0.001), spleen (P<0.001) and lung tissue (P<0.01) GSH levels were found to be higher in the carnitine group. In renal, liver and lung tissues, the MDA levels increased in the CM group (P<0.001). The histopathological findings showed that L-carnitine may have a preventative effect in alleviating the negative effects of CIN. Similar to this, L-carnitine may play a major role in the stability of the antioxidant status in the kidney, liver, spleen and lung of the CIN rat model.

Carnitine supplementation to obese Zucker rats prevents obesity-induced type II to type I muscle fiber transition and favors an oxidative phenotype of skeletal muscle.

BackgroundIn the present study, we tested the hypothesis that carnitine supplementation counteracts obesity-induced muscle fiber transition from type I to type II.Methods24 obese Zucker rats were randomly divided into two groups of 12 rats each (obese control, obese carnitine) and 12 lean Zucker rats were selected for lean control group. A control diet was given to both control groups and a carnitine supplemented diet (3 g/kg diet) was given to obese carnitine group for 4 wk. Components of the muscle fiber transformation in skeletal muscle were examined.ResultsThe plasma level of carnitine were lower in the obese control group compared to the lean control group and higher in the obese carnitine group than in the other groups (P < 0.05). Plasma concentrations of triglycerides and non-esterified fatty acids were increased in obese animals compared to lean animals and the obese carnitine group had lower level compared to the obese control group (P < 0.05). The obese carnitine group had an increased number of type I muscle fibers and higher mRNA levels of type I fiber-specific myosin heavy chain, regulators of muscle fiber transition and of genes involved in carnitine uptake, fatty acid transport, β-oxidation, angiogenesis, tricarboxylic acid cycle and thermo genesis in M. rectus femoris compared to the other groups (P < 0.05).ConclusionThe results demonstrate that carnitine supplementation to obese Zucker a rat counteracts the obesity-induced muscle fiber transition and restores the muscle oxidative metabolic phenotype. Carnitine supplementation is supposed to be beneficial for the treatment of elevated levels of plasma lipids during obesity or diabetes.

Levo-carnitine reduces oxidative stress and improves contractile functions of fast muscles in type 2 diabetic rats.

Metabolic derangements in type 2 diabetes mellitus (T2DM) are likely to affect skeletal muscle contractile functions adversely. Levo-carnitine improves muscle contractile functions in healthy humans and rats and corrects metabolic derangements in T2DM. Therefore, it is likely to improve muscle contractile functions in T2DM as well. This study was designed to determine the effect of levo-carnitine on serum levo-carnitine levels, oxidative stress and contractile parameters of fast muscle in T2DM. Ninety Sprague-Dawley rats were randomly divided into three equal groups. Healthy rats served as the controls, while T2DM was induced in diabetic and carnitine groups. The carnitine group was administered levo-carnitine 200 mg/kg/day intraperitoneally for 6 days. At 28th day, extensor digitorum longus muscles were removed and their functions were assessed using iWorx data acquisition unit (AHK/214). Blood obtained by intra-cardiac sampling at 28th day was used for estimation of serum malondialdehyde (MDA) and levo-carnitine levels. Maximum isometric twitch tension, time-to-peak twitch tension and time-to-relax to 50% of the peak twitch tension were not significantly different amongst the groups. Carnitine group showed significant improvement in maximum fused tetanic tension, maximum fused tetanic tension after fatigue protocol and recovery from fatigue after 5 minutes of rest period compared to the diabetic group. Serum MDA levels were reduced, while serum levo-carnitine levels were elevated significantly in carnitine group as compared to the diabetic group. Levo-carnitine supplementation increases serum levo-carnitine levels which decreases oxidative stress. This action improves contractile force but delays fatigue in fast muscles of diabetic rats.

Sıçanlarda Uzun Süreli Böbrek İskemisi ve Reperfüzyon Hasarında L-Karnitinin Etkileri

Objective: Free radicals and nitric oxide play an important role in the pathogenesis of acute kidney injury (AKI) induced by ischemia and reperfusion (IR). Despite the protective effects of L-carnitine on renal ischemia reperfusion injury, reports are lacking on its effects on anemia and the erythrocyte antioxidant status of long-term post IR injury in the rat kidney. In the present study, we aimed to investigate the effects of L-carnitine on long-term IR injury in rat kidney. Material and Methods: Male Wistar Albino rats were divided into three groups (eight rats each) as Sham, IR (60 minutes of bilateral ischemia and 168 hours reperfusion) and IR+L-carnitine (intraperitoneally; 300 mg/kg/day for 7 days) groups. Anemia, kidney function, lipid peroxidation and kidney and erythrocyte antioxidant enzyme activities as well as expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were examined. The kidneys were histologically evaluated. Results: L-carnitine treatment attenuated IR-induced histological alteration and reduced iNOS activitiy, increased eNOS activity, reduced urea and creatinine (each p=0.001), decreased malondialdehide levels (p=0.001) and increased both kidney and erythrocyte antioxidant enzymes activitiy and glutathione levels (p=0.001). Hematocrit was significantly increased (p=0.038). Conclusion: Our results show that L-carnitine plays a protective role in the pathogenesis of renal injury induced by IR. In addition, L-carnitine may ameliorate the anemia observed after renal IR injury.