Does L-carnitine prevent cadmium-induced damage in gastrointestinal contractility and histological changes in prepubertal rat / ¿La L-carnitina previene el daño inducido por cadmio en la contractilidad gastrointestinal y los cambios histológicos en ratas prepúberes?

SUMMARY: Cadmium (Cd) is the industrial and environmental toxic heavy metal which is found in air, water and soil. Cd, adversely affects many organs in humans such as kidney, intestine, liver, testis and lungs. L-carnitine (LC) is an important agent that plays essential role in energy metabolism. In our study, we aimed to work out whether LC application has any protective effect on intestinal contractility and morphologic damage of prepubertal rat duodenum on Cd-induced toxicity. Twenty eight prepubertal female Wistar rats were divided into four groups. The first group is control (C), second group; Cd group; Cadmium chloride was given 2 mg/kg 28 days with a one-day break by i.p. The third group; Cd+LC, which cadmium chloride was given 2 mg/kg i.p. and LC was given orally by gastric lavage. The LC dose was given as 75 mg/kg. The fourth group; LC, which only LC was given orally. The intestinal segments were isolated and suspended in tissue bath. Contractile responses were induced by acetylcholine (ACh) and relaxation was achieved with phenylephrine. Also the segments were examined for histological changes by light microscopy. Ach-induced contractions were higher in Cd+LC, LC, and control group compared to the Cd group in duodenal segments. The phenylephrine-induced relaxations were lower in Cd groups as compared with Control, Cd+LC and LC group in duodenal segments. In Cd group intestinal morphology was observed to be severely damaged whereas in Cd+LC group the damage was noticeably lower. Cd administration caused severe cellular damage and decreased gastrointestinal motility. Treatment with the LC has affected the gastrointestinal contractility and reduced the damage in intestinal morphology, which occured after Cd application.

El cadmio (Cd) es el metal pesado tóxico industrial y ambiental que se encuentra en el aire, el agua y el suelo. El Cd afecta negativamente a muchos órganos humanos, como los riñones, los intestinos, el hígado, los testículos y los pulmones. La L-carnitina (LC) es un agente importante que juega un rol esencial en el metabolismo energético. El objetivo de este estudio fue determinar si la aplicación de LC tiene algún efecto protector sobre la contractilidad intestinal y el daño morfológico del duodeno de rata prepuberal sobre la toxicidad inducida por Cd. Veintiocho ratas Wistar hembras prepúberes se dividieron en cuatro grupos. El primer grupo control (C), segundo grupo; grupo cd; Se administró cloruro de cadmio 2 mg/kg durante 28 días con un descanso de un día por vía i.p. El tercer grupo; Cd+LC, al que se administró cloruro de cadmio 2 mg/kg i.p. y LC se administró por vía oral mediante lavado gástrico. La dosis de LC se administró como 75 mg/kg. El cuarto grupo; LC, al cual solo LC se administraba por vía oral. Los segmentos intestinales fueron aislados y suspendieron en baño de tejido. Las respuestas contráctiles fueron inducidas por acetilcolina (ACh) y la relajación se logró con fenilefrina. También se examinaron los segmentos en busca de cambios histológicos mediante microscopía óptica. Las contracciones inducidas por Ach fueron mayores en Cd+LC, LC y el grupo control en comparación con el grupo Cd en los segmentos duodenales. Las relajaciones inducidas por fenilefrina fueron menores en los grupos Cd en comparación con el grupo Control, Cd+LC y LC en los segmentos duodenales. En el grupo Cd se observó que la morfología intestinal estaba severamente dañada mientras que en el grupo Cd+LC el daño fue notablemente menor. La administración de Cd causó daño celular severo y disminución de la motilidad gastrointestinal. El tratamiento con LC afectó la contractilidad gastrointestinal y redujo el daño en la morfología intestinal, que ocurría después de la aplicación de Cd.

The effects of L-carnitine on gastrointestinal contractility and histological changes in rat intestinal ischemia-reperfusion Injury / Efectos de la l-carnitina sobre la contractilidad gastrointestinal y los cambios histológicos en la lesión por isquemia-reperfusión intestinal de rata

SUMMARY: Ischemia-reperfusion (I/R) of the small intestine causes serious abdominal pathologies including tissue dysfunction and organ failure. L-carnitine (L-C), a powerful antioxidant, may help lessen the severity of these pathological effects since it plays a key role in energy metabolism. In this work we aimed to study the effects of L-C on the isolated ileal and duodenal contractility and histological changes in intestinal ischemia and reperfusion injury. Twenty eight Wistar rats were divided into four groups. The first group is the control group. Second group, I/R group, had rats submitted to 45-minutes of intestinal ischemia and to 45-minutes reperfusion. The third group, I/R+ L-C group, rats were treated with L-C 5 minutes before reperfusion and than submitted to ischemia. The fourth group, included rats that were treated with L-C without ischemia or reperfusion. Intestinal ischemia was conducted by obstructing superior mesentery arteries by silk loop. The ileal and duodenal segments were isolated and suspended in tissue bath. Contractile responses were induced by acetylcholine (Ach) and relaxation was achieved with phenylephrine. At the same time the terminal ileal and duodenal segments were examined for histological changes. Ach-induced contraction responses were higher in the I/R+L-C group, the L-C group, and the control group compared to the I/R group, in both ileal and duodenal segments. On the other hand, the phenylephrine-induced relaxations were higher in the I/R+L-C and L-C groups, especially in duodenal segments. In I/R group intestinal morphology was observed to be severely damaged whereas in I/R+L-C group the damage was noticeably lower possibly due to protective properties of L-C. I/R injury caused severe cellular damage response within the muscularis resulting in decreased gastrointestinal motility. Treatment with the L-C has significantly affected the gastrointestinal contractility. Also L-C treatment reduced the damage in intestinal morphology that occurs after IR injury.

RESUMEN: La isquemia-reperfusión (I/R) del intestino delgado provoca graves patologías abdominales que incluyen disfunción tisular y falla orgánica. La L-carnitina (L-C), un poderoso antioxidante, puede ayudar a disminuir la gravedad de estos efectos patológicos, ya que desempeña un papel clave en el metabolismo energético. El objetivo de este trabajo fue estudiar los efectos de L-C sobre la contractilidad ileal y duodenal aislada y los cambios histológicos en la lesión por isquemia y reperfusión intestinal. Se dividieron 28 ratas Wistar en cuatro grupos. El primer grupo fue el control. El segundo grupo, grupo I/R, de ratas sometidas durante 45 minutos de isquemia intestinal y a 45 minutos de reperfusión. El tercer grupo, grupo I/R+ L-C, las ratas se trataron con L-C, 5 minutos antes de la reperfusión y luego se sometieron a isquemia. El cuarto grupo, las ratas fueron tratadas con L-C sin isquemia ni reperfusión. La isquemia intestinal se realizó obstruyendo la arteria mesentérica superior con un asa de seda. Los segmentos ileal y duodenal se aislaron y suspendieron en un baño de tejido. Las respuestas contráctiles fueron inducidas por acetilcolina (Ach) y la relajación se logró con fenilefrina. Al mismo tiempo, se examinaron cambios histológicos de los segmentos del íleon terminal y del duodeno. Las respuestas de contracción inducidas por Ach fueron mayores en el grupo I/R+L-C, el grupo L-C y el grupo control en comparación con el grupo I/R, tanto en el segmento ileal como en el duodenal. Por otra parte, las relajaciones inducidas por fenilefrina fueron mayores en los grupos I/R+L-C y L-C, especialmente en los segmentos duodenales. En el grupo I/R se observó que la morfología intestinal estaba dañada significativamente, mientras que en el grupo I/R+L-C el daño fue notablemente menor, posiblemente debido a las propiedades protectoras de L-C. La lesión por I/R causó una respuesta de daño celular severo dentro de la capa muscular que resultó en una disminución de la motilidad gastrointestinal. El tratamiento con L-C afectó significativamente la contractilidad gastrointestinal. Por otra parte, el tratamiento L-C redujo el daño en la morfología intestinal que ocurre después de la lesión por IR.

Eficacia y seguridad de coenzoma Q10, carnitina y riboflavina en pacientes con enfermedades mitocondriales / Efficacy and safety of coenzyme Q10, carnitine and riboflavin in patients with mitochondrial diseases

INTRODUCCIÓN: Antecedentes: El presente dictamen expone la evaluación de tecnología de la eficacia y seguridad de la coenzima Q10, carnitina y riboflavina respecto a su uso en pacientes con enfermedades mitocondriales. Aspectos Generales: Las mitocondrias son organelas complejas de doble membrana que cuentan con un ADN propio, heredado de la madre. Subojetivo es producir energia a partir de los nutrientes en fora de calor y ATP, mediante la respiración. El proceso por el cual se produce la energía es conocido como fosforilación oxidativa y se lleva a cabo en la cadena respiratoria de las mitocondrias, también llamada cadena transportadora de electrones. Tecnologia Sanitária de Interés: Coenzima Q10: La coenzima Q10, también conocida como ubiquinona, es una quinona soluble en grasas , sintetizada en la mitocondria y que se encuentra presente en la membranas celulares. La coenzima Q'0 endógena es producida por el organismo como parte de la vía de producción del colestereol, mientras que la exógena es ingerida por la dieta como ubiquinona (forma oxidada) y ubuquinol (forma reducida). Esta molécula se encuentra presente en todas las células del organismo, en mayor concentración en el tejido del cerebro, corazón, riñones, e hígado. Carnitina: La carnitina, presente en el organismo y en los alimentos como I-carnitina, es un aminoácido sintetizado en el tejido muscular, renal y hepático a partir de los aminoácidos l-lisina yl-metionina. Existen fuentes exógenas de l-carnitina como las carnes rojas, el pescado, el pollo e la leche. Esta molécula cumple una función importante en el metabolismo de ácidos grasos, ya que promueve la utilización de la grasa almacenada en el organismo como fuente de energia. Especificamente, la L-carnitina es un transportador de lípidos que permite el ingreso de las cadenas de ácidos grasos a la matriz mitocondrial para ser convertidos en energía a través del proceso de la beta-oxidación. Riboflavina: La riboflavina (vitamina B2) es una vitamina hidrosolubre que se encuentra la manera natural en los alimentos de origen animal y vegetal, y puede ser producida también por la microbiota intestinal. Esta vitamina se absorve en el intestino delgado proximal y, cuando es consumida en exceso, es excretada por la orina y/o almacenada en concetraciones reducidas en el hígado, riñones, y corazón. METODOLOGÍA: Estrategia de Búsqueda: Se realizó una búsqueda de literatura científica en relación a la eficacia y seguridad del uso de la coenzima Q10, carnitina y riboflavina en pacientes con enfermedades mitocondriales (EM). Sedio preferencia a guías de práctica clínica, revisiones sistemáticas con o sin meta-análisis y ensayos clínicos aleatrorizados. RESULTADOS: Sinopsis de la Evidencia: Se realizó la busqueda bibliográfica y de evidencia científica que sustente el uso de coenzima Q10, carnitina y riboflavina en pacientes con diganóstico de enfermedades mitocondriales (EM). CONCLUSIONES: En la presente evaluación de tecnología sanitária se presenta a la evidencia recabada sobre el beneficio de la coenzima Q10, carnitina y riboflavina en pacientes con enfermedades mitocondriales. La evidencia encontrada que evalúa el uso de estos compuestos en pacientes con enfermedades mitocondriales es escasa. Se ha identificado evidencia proveniente de tres ensayos clínicos y un estudio obervacional. Ninguno de los estudios evaluó los tres suplementos en conjunto como una sola intervención. El Instituto de evaluación en Salud e Investigación-IETSI, aprueba el uso de la coenzima Q10, carnitina y riboflavina en pacientes con enfermedades mitocondriales. El presente Dictamen Preliminar tiene una vigencia de dos años a partir de la fecha de publicación.

Impact of vigorous exercise on serum levels of L-Carnitine in prisoners in Colombia / Impacto del ejercicio vigoroso sobre los niveles séricos de L-Carnitina en prisioneros de Colombia

Objective To assess the effect of a program of vigorous physical exercises on the serum concentration of free and total L-carnitine, in male inmates at a prison in Boyacá, Colombia. Methods Pre-post intervention population-based study. 44 male prisoners with overweight and/or obesity, from a jail in Boyacá, Colombia were randomly assigned into two groups: an intervention group and a control group. The intervention consisted in participating in a vigorous exercise program over twelve weeks. Anthropometric measures and levels of free and total L-carnitine were every four weeks. Results There were significant increases in serum levels of free and total L-carnitine in the intervention group compared to the control group. Concurrently, in this group there was a reduction in body mass index (BMI), while in the control group there were no changes. Conclusion In overweight and/or obese patients, the routine practice of vigorous exercise plus caloric restriction offers significant benefits in reducing body fat volumes through the mechanisms of energetic consumption of long chain fatty acids.(AU)

Objetivo Evaluar el efecto de un programa de ejercicio físico intenso sobre las concentraciones séricas de L-Carnitina libre y total, en varones recluidos en una prisión de Boyacá, Colombia. Métodos Estudio de intervención antes - después, de base poblacional. 44 internos con sobrepeso y/o obesidad, de una prisión en Boyacá, Colombia, fueron aleatoriamente asignados a dos grupos: Uno de intervención y uno de control. La intervención consistió en un programa de práctica sistemática de ejercicio intenso, durante doce semanas continuas. Cada cuatro semanas se realizaron mediciones antropométricas y se determinaron los niveles séricos de L-Carnitina libre y total. Resultados Hubo un incremento significativo en los niveles séricos de L-Carnitina libre y Total en el grupo de intervención, comparado con lo registrado en el grupo control; simultáneamente, en el grupo de intervención se registró disminución en el índice de masa corporal (IMC), mientras que en el grupo control no se registraron cambios. Conclusión En presencia de sobrepeso y/o obesidad, la práctica rutinaria de ejercicios físicos intensos además de la restricción calórica, ofrece significativos beneficios en la reducción del volumen de grasa corporal por el mecanismo de consumo energético de los ácidos grasos de cadena larga.(AU)

Suplementação oral de L-carnitina associada ao treinamento físico e muscular respiratório na doença pulmonar obstrutiva crônica: estudo preliminar / Oral supplementation of L-carnitine combined with exercise and respiratory training in patients with chronic obstructive pulmonary disease: preliminary study

Avaliar os efeitos da suplementação oral de L-carnitina associada ao treinamento físico e muscular respiratório na doença pulmonar obstrutiva crônica (DPOC). Participaram 14 voluntários com idade de 65±10,4 anos e diagnóstico clínico de DPOC moderado, classificados de acordo com a espirometria prévia. Os voluntários foram divididos em grupo treino esteira (GTE) e grupo treino muscular respiratório (GTMR). Realizaram o teste de caminhada de seis minutos (TC6'), teste de caminhada com carga progressiva (TCP), avaliação nutricional do índice de massa corpórea (IMC), dose diária recomendada de L-carnitina, pressões inspiratórias (PImáx) e expiratórias máximas (PEmáx). Fizeram 30 min de caminhada em esteira, 3 vezes/semana por 10 semanas, e o GTMR realizou, ainda, 10 min de treinamento muscular inspiratório (Threshold® IMT) e 10 min de treinamento muscular expiratório (Threshold® PEP) à 50% da PImáx e PEmáx ajustados semanalmente. Após 10 semanas, foram reavaliados. No TC6' pré e pós-programa de treinamento físico, as variáveis alteradas foram: distância percorrida (DP), frequência cardíaca (FC) final, pressão arterial sistólica (PAS) final, pressão arterial diastólica (PAD) final e Borg final no GTMR, no GTE as variáveis alteradas foram FC repouso, FC final, PAS final, Borg repouso e DP. Comparando os grupos no TC6, o GTE apresentou FC final, PAD final e Borg final maiores do que o GTMR na reavaliação; já no TCP, a FC final, PAS final, Borg final foram maiores no GTE, e DP foi maior no GTMR. Na avaliação respiratória, a PEmáx foi maior no GTMR na reavaliação. O treino aeróbio e suplementação de L-carnitina na DPOC otimizou a performance, a capacidade física e a tolerância ao esforço.

To evaluate the effects of oral supplementation of L-carnitine associated with physical and respiratory muscles training in chronic obstructive pulmonary disease (COPD). Participated 14 COPD volunteers (65±10.4 years), divided in group training mat (GTM) and respiratory muscle training group (RMTG). Passed by the six minute walk test (6MWT) and shuttle walk test (SWT), nutritional assessment of body mass index (BMI), dose recommended daily L-carnitine and evaluation of the inspiratory muscle training (IMT) and expiratory muscle training (EMT). They made 30 min walk on a treadmill 3 times/week for 10 weeks, and the RMTG also carried out 10 min with inspiratory muscle training (Threshold® IMT) and 10 min with expiratory muscle training (Threshold® PEP) with 50% of the MIP and MEP adjusted weekly. After 10 weeks, the volunteers were reevaluated. In 6MWT pre and post physical training programs, the variables changed were distance travelled (DT), final cardiac frequency (FCF), final systolic blood pressure (FSBP), diastolic blood pressure (DBP) and final Borg in RMTG. At GTM the variables changed were initial CF, final CF, SBP final, initial Borg and DT. Comparing the groups, we showed that in 6MWT, GTM presented final CF, final DBP and final Borg higher than RMTG in reevaluation. In shuttle walk test, the final SBP and final Borg were higher in GTM, and DT was higher in RMTG. In respiratory evaluation, the MEP was higher in RMTG in reevaluation. The aerobic training and L-carnitine supplementation in COPD patients presented performance optimization, improvement in physical capacity and greater exercise tolerance.

Prevention of di [2-ethylhexyl] phthalate-induced testicular disturbance in mice by Co-administration of L-carnitine

di [2-ethylhexyl] phthalate [DEHP] is widely used in the plastic industry and can induce reproductive toxicity. On the other hand, L-carnitine [LC] plays a crucial role in sperm metabolism and maturation. This study evaluates the effect of LC on body and testis weight, testis tissue, count, motility, viability, morphology, and chromatin quality of epididymal sperm, testicular spermatid number [TSN] per gram testis and daily sperm production [DSP] in LC-treated mice. In this experimental study, adult male NMRI mice [mean age: 4 weeks] were given doses of DEHP and LC by gavaging for 2 weeks. All samples were assessed according to World Health Organization [WHO] criteria. Sperm morphology was assessed using Papanicolaou staining and sperm chromatin quality by aniline-blue staining. The left testes were fixed in Bouin? solution for histological examination and the end slices were stained with hematoxylin and eosin [H and E]. The right testes were homogenized, and then TSN and DSP were calculated with an improved Neubauer haemocytometer and respective frames. Paired t-test, ANOVA, and Kruskal-Wallis tests were utilized for data analysis. Co-administration of DEHP and LC not only prevented significant gains in testicular weight, but also maintained the sperm's normal morphology and chromatin quality [p<0.05]. In addition, LC recovered histological changes, TSN, DSP, and sperm count. These results demonstrated that oral administration of LC partially or generally protects spermatogenesis from DEHP-toxicity in mice

Effects of L-carnitine on inducible nitric oxide synthase, insulin like growth factor-1 gene expression and insulin receptor substrate-1 in kidney tissues of insulin resistant rats induced by high fructose feeding

Metabolism of high dietary fructose induces insulin resistance and metabolic adaptation including changes in gene expression. The present study was designed to elucidate the effects of L-Carnitine [CA] on the renal alterations as well as gene expression such as inducible Nitric Oxide Synthase [iNOS]. Insulin-like Growth Factor-1 [IGF-1], insulin receptor substrate-1 [IRS-1] in kidney tissues of rats fed on high fructose diet. 24 male Wister rats of body weight 120-160 g were divided into 3 groups of 8 rats each. Group 1 received control diet, while group 2 and 3, rats received high fructose diet [60 g/100 g diet]. Group 3, after 2 weeks of fructose feeding animals were treated with CAR [300 mg/kg body weight/day i.p]. At the end of the experimental period [30 days], serum levels of glucose, insulin, Triacylglycerol [TG] and cholesterol were determined. Renal contents of cholesterol, triacylglycerol, Malondialdehyde [MDA] and nitric oxide products were determined. Gene expressions of iNOS, IGF-1 as well as IRS-1 were also assayed in kidney tissues of the experimental rats feed on high fructose diet. Rats fed on high fructose diet showed disturbance in insulin action and formed an animal model of insulin resistance. Fructose fed rats showed increase in renal gene expression of iNOS and decrease in both IGF-1 mRNA and IRS-1 receptor compared to control rats. The administration of CA to rat model of insulin resistance, mitigated the adverse effects of fructose load. Thus the observed abnormalities in gene expression associated with fructose feeding were brought to near-normal levels as compared with untreated rats. L-carnitine normalized the serum and renal lipid alterations as well as gene expression [iNOS, IGF-1] and IRS-1 in this nutritional experimental model

Effects of L-carnitine and taurine on associated biochemical changes in alloxan induced diabetic rats

The aim of the present study was to investigate the beneficial effects of L-carnitine and taurine in healthy and alloxan induced diabetes mellitus in rats. Results showed that diabetic rats had significant increase in the levels of plasma glucose, malondialdehyde [MDA], urea, creatinine and the activity of serum asparate aminotransferase and alanine aminotransferase as compared to normal control rats. While, blood glutathione [GSH] content and erythrocyte superoxide dismutase [SOD] activity were significantly lowered. The elevated plasma glucose, MDA, AST, ALT, urea and creatinine levels of diabetic rats were significantly reduced by treatment for 6weeks with L-carnitine and taurine. In addition, normal healthy rats fed on the balanced diet plus L-carnitine and taurine showed significant increase in blood glutathione [GSH] content and erythrocyte superoxide dismutase [SOD] activity as compared with healthy control. It was concluded that dietary administration of L-carnitine and taurine reduces, delays or even prevent oxidative stress in diabetic rats

A suplementação de L-carnitina não promove alterações na taxa metabólica de repouso e na utilização dos substratos energéticos em indivíduos ativos / The supplementation of L-carnitine does not promote alterations in the resting metabolic rate and in the use of energetic substrates in physically active individuals

OBJETIVO: Avaliar o efeito da suplementação de L-carnitina, por 30 dias, sobre a taxa metabólica de repouso (TMR) e oxidação de ácidos graxos livres (AGL), em repouso e exercício. SUJEITOS E MÉTODOS: Vinte e um voluntários ativos (40 a 58 anos) com sobrepeso foram randomizados em dois grupos: suplementado (GS; N = 11; 1,8 g/dia de L-carnitina) e placebo (GP; N = 10; maltodextrina). Foi feita avaliação da ingestão calórica, antropometria, determinação da TMR, VO2máx, quociente respiratório e AGL plasmáticos. RESULTADOS: Não houve diferença significativa na ingestão (-244,66 vs. -126,00 kcal/dia), composição corporal (-0,07 vs. -0,17 kg/m²), TMR (0,06 vs. -0,02 kcal/ dia), quociente respiratório em repouso (3,69 vs. -1,01) e exercício (0,01 vs. -0,01) e VO2máx (0,50 vs. 1,25 mL/kg/min) para o grupo GS em relação ao GP. Houve aumento dos AGL em repouso no GP (0,27), porém sem diferenças no exercício para os grupos. CONCLUSÃO: Não houve efeito da L-carnitina em nenhuma das variáveis analisadas no estudo.

PURPOSE: To investigate the effects of L-carnitine supplementation, over thirty days, on the resting metabolic rate (RMR) and oxidation of free fatty acids (FFA) under rested or exercised conditions. SUBJECTS AND METHODS: Twenty-one overweight active volunteers (40 to 58 years old) were randomized into two groups: supplemented (GS; N = 11; 1,8 g/day of L-carnitine) or placebo (GP; N = 10; maltodextrin). Caloric intake, anthropometry, RMR, VO2max, respiratory exchange ratio and plasma FFA were measured. RESULTS: No significant changes were found in the caloric intake (-244,66 vs. -126,00 kcal/day), body composition (-0.07 vs. -0.17 kg/m²), RMR (0.06 vs. -0.02 kcal/day), respiratory exchange ratio at rest (3.69 vs. -1.01) and exercise (0.01 vs. -0.01) or VO2max (0.50 vs. 1.25 mL/kg/min) between GS and GP. Plasma FFA levels were increased under resting conditions only in the GP group (0.27), but no significant changes were observed before or after physical activity in any of the groups. CONCLUSION: Supplementation with L-carnitine caused no changes in the variables analyzed in this study.

Protective effect of L-carnitine against carbon tetrachloride-induced liver injury in rats

Oxidative damage is involved in the pathogenesis of various, hepatic injuries. In the present study the capacity of L-carnitine as an antioxidant to protect against carbon tetrachloride [CCl[4]]-induced oxidative stress and hepatotoxicity in rats was Cairo. Egypt investigated. Daily oral administration of CCl[4]100 mg/kg in corn oil for 4 weeks produced a marked significant elevation in serum, alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], lactate dehydrogenase [LDH], and alpha fetoprotein [AFP]. Hepatic lipid peroxidation, quantified as malondialdehyde [MDA] was significantly increased, while the activity of the two antioxidant enzymes; glutathione peroxidase [GPx] and superoxide dismutase [SOD] in the liver were significantly reduced. Histopathological and histochemical analyses of the liver of rats treated with CCl[4] revealed centrilobular necrosis with lymphocytic infiltration between hepatocytes. The hepatocytes were damaged in the form of fatty degeneration, vacuolization, ballooning with bundles of fibrous tissue surrounding the portal tracts and dissecting the parenchyma. Concurrent administration of L-carnitine [50 mg/kg/day; s.c.] with CC!4 for 4 weeks produced a significant reduction of aminotransferases together with normalization of ALP and LDH activities as well as AFP level. The biochemical parameters of oxidative stress were improved. Hepatic MDA concentration was significantly reduced, while the activities of the hepatic antioxidant enzymes GPx and SOD were significantly increased. These effects were paralleled with an improvement of the histopathological changes induced by CCl[4], where the hepatic architecture was preserved by L-carnitine treatment. Therefore, the results of this study show that L-carnitine can be proposed to protect the liver against CCl[4]-induced oxidative damage in rats, and the hepatoprotective effect might be correlated with its antioxidant and free radical scavenger effects

Results of a single blind, randomized, placebo-controlled clinical trial to study the effect of intravenous L-carnitine supplementation on health-related quality of life in Indian patients on maintenance hemodialysis.

BACKGROUND: Carnitine insufficiency is responsible for various co-morbid conditions in maintenance hemodialysis (MHD) patients. L-carnitine supplementation is expected to improve the quality of life (QoL) of patients on MHD. AIMS: To study the effect of L-carnitine supplementation on QoL of Indian patients on MHD. SETTING AND DESIGN: This was a single (patient) blind, randomized, placebo-controlled clinical trial conducted on patients on MHD attending hemodialysis unit of the study center. MATERIALS AND METHODS: Twenty patients on MHD suffering from hemodialysis-related symptoms were randomly assigned to receive intravenous L-carnitine 20 mg/kg or placebo after every dialysis session for 8 weeks. SF36 (Short Form with 36 questions) score for QoL, laboratory investigations and dialysis related symptoms were recorded at baseline and after 8 weeks. Improvement in QoL, laboratory parameters and dialysis related symptoms in the two groups after 8 weeks was compared. STATISTICAL ANALYSIS USED: Depending on normality of data, unpaired T test or Mann Whitney U test was used for comparison of change (8 weeks-baseline) in SF36 scores and laboratory parameters observed in the two groups. RESULTS: L-carnitine supplementation increased total SF36 score by 18.29 +/- 12.71 (95% CI: 10.41 to 26) while placebo resulted in reduction in total SF36 score by 6.4 +/- 16.39 (95% CI: -16.59 to 3.73). L-carnitine also resulted in significant increase in hemoglobin and serum albumin and decrease in serum creatinine as compared to placebo. More patients were relieved of dialysis related symptoms in L-carnitine group. CONCLUSION: Intravenous L-carnitine supplementation improves QoL in patients on MHD.

L-carnitine as an ergogenic aid for patients with chronic obstructive pulmonary disease submitted to whole-body and respiratory muscle training programs

The effects of adding L-carnitine to a whole-body and respiratory training program were determined in moderate-to-severe chronic obstructive pulmonary disease (COPD) patients. Sixteen COPD patients (66 ± 7 years) were randomly assigned to L-carnitine (CG) or placebo group (PG) that received either L-carnitine or saline solution (2 g/day, orally) for 6 weeks (forced expiratory volume on first second was 38 ± 16 and 36 ± 12 percent, respectively). Both groups participated in three weekly 30-min treadmill and threshold inspiratory muscle training sessions, with 3 sets of 10 loaded inspirations (40 percent) at maximal inspiratory pressure. Nutritional status, exercise tolerance on a treadmill and six-minute walking test, blood lactate, heart rate, blood pressure, and respiratory muscle strength were determined as baseline and on day 42. Maximal capacity in the incremental exercise test was significantly improved in both groups (P < 0.05). Blood lactate, blood pressure, oxygen saturation, and heart rate at identical exercise levels were lower in CG after training (P < 0.05). Inspiratory muscle strength and walking test tolerance were significantly improved in both groups, but the gains of CG were significantly higher than those of PG (40 ± 14 vs 14 ± 5 cmH2O, and 87 ± 30 vs 34 ± 29 m, respectively; P < 0.05). Blood lactate concentration was significantly lower in CG than in PG (1.6 ± 0.7 vs 2.3 ± 0.7 mM, P < 0.05). The present data suggest that carnitine can improve exercise tolerance and inspiratory muscle strength in COPD patients, as well as reduce lactate production.

Novas terapias ergogênicas no tratamento da doença pulmonar obstrutiva crônica / New treatments for chronic obstructive pulmonary disease using ergogenic aids

A doença pulmonar obstrutiva crônica é considerada, atualmente, uma doença sistêmica, cujas alterações estruturais e metabólicas podem levar à disfunção muscular esquelética. Esta afeta negativamente o desempenho muscular respiratório e periférico, a capacidade funcional, a qualidade de vida relacionada à saúde e mesmo a sobrevida. A indicação de suplementação de substâncias ergogênicas para pacientes com doença pulmonar obstrutiva crônica baseia-se no fato de que estas drogas podem evitar, ou minimizar, o catabolismo e/ou estimular a síntese protéica, diminuindo a depleção de massa muscular e aumentando a capacidade de exercício. A presente revisão sumariza o conhecimento disponível acerca da utilização de esteróides anabolizantes, creatina, L-carnitina, aminoácidos de cadeia ramificada e hormônio de crescimento em pacientes com doença pulmonar obstrutiva crônica. A vantagem do uso dessas substâncias ergogênicas parece residir no aumento da massa magra e/ou na indução de modificações bioenergéticas. Nesse contexto, a maior experiência acumulada é com os esteróides anabolizantes. Entretanto, os benefícios clínicos em relação à melhora da capacidade de exercício e força muscular, bem como os efeitos na morbimortalidade, não foram, até a presente data, consistentemente demonstrados. A suplementação ergogênica pode vir a se constituir numa ferramenta adjuvante para o tratamento de pacientes com doença pulmonar obstrutiva crônica avançada, especialmente naqueles com depleção muscular e/ou fraqueza periférica.

Efeitos da suplementação oral de L-carnitina associada ao treinamento físico na tolerância ao exercício de pacientes com doença pulmonar obstrutiva crônica / Influence of oral L-carnitine supplementation combined with physical training on exercise tolerance in patients with chronic obstructive pulmonary disease

INTRODUÇAO: Pacientes portadores de doença pulmonar obstrutiva crônica apresentam redução da tolerância ao exercício físico, principalmente devido à limitação ventilatória. A L-carnitina tem sido utilizada com o objetivo de melhorar a capacidade aeróbia de pacientes com doenças crônicas, porém não existem estudos em pacientes portadores de doença pulmonar obstrutiva crônica. OBJETIVO: Avaliar a influência da suplementação de L-carnitina, associada ao treinamento físico por seis semanas, três vezes por semana em pacientes portadores de doença pulmonar obstrutiva crônica. MÉTODO: A amostra foi constituída de 30 pacientes portadores de doença pulmonar obstrutiva crônica (69 ± 7 anos) com volume expiratório forçado no primeiro segundo < 65 por cento do previsto, dividida em três grupos de 10 pacientes: grupo 1 com treinamento físico e suplementação com 2g/dia de L-carnitina, grupo 2 que recebeu treinamento físico e placebo e grupo 3 que não foi submetido a treinamento físico e recebeu 2g/dia de L-carnitina. Os pacientes foram submetidos a avaliação espirométrica, a teste de caminhada de seis minutos e à mensuração dos níveis plasmáticos de carnitina livre no inicio e no final do estudo. RESULTADOS: Foi constatado aumento significativo (p < 0,05) da distância percorrida no teste de caminhada de seis minutos somente nos pacientes dos dois primeiros grupos (de 421 ± 100 para 508 ± 80,7 e de 496 ± 78,7 para 526 ± 64,3 respectivamente). Além disso, com intensidade de exercício semelhante, a subida da freqüência cardíaca foi menor no grupo 1 quando comparado com o grupo 2. As variáveis espirométricas, a saturação da oxihemoglobina e a dispnéia não se alteraram em nenhum dos grupos estudados. Os valores de L-carnitina livre no plasma aumentaram somente nos pacientes do terceiro grupo (59,2 ± 13,8 para 102,3 ± 15,32mmol/L). CONCLUSAO: A L-carnitina associada ao treinamento físico pode proporcionar maior tolerância ao exercício em pacientes com doença pulmonar obstrutiva crônica.

L-carnitine moderately improves the exercise tolerance in chronic stable angina.

OBJECTIVES: To study the safety and efficacy (with reference to exercise ECG testing) of oral L-carnitine in chronic stable angina. METHODS: Forty-seven patients, 30 men and 17 women, aged 56 +/- 8 years, were randomized to receive L-carnitine (n = 28) or placebo (n = 19) in the dose of 2 g/day for 3 months. The adjuvant treatment was not changed during the study. Patients were evaluated by computerized stress test (CST) done at the beginning and end of the trial. The parameters assessed were exercise duration, time to onset of ST changes, total ST score at peak exercise, rate-pressure product at peak exercise, and time needed for the ST changes to recover to baseline. RESULTS: The two groups were comparable at the beginning of the study. There was no change in the CST parameters in the placebo group at the end of 3 months. In the L-carnitine group there was a statistically significant improvement in the exercise duration from 7.8 +/- 2.2 min to 8.6 +/- 1.8 min (p = 0.006) and in the time needed for the ST changes to revert to baseline from 7.2 +/- 3.9 min to 5.7 +/- 3.8 min (p = 0.019). No change was noted in the time to onset for ST depression, ST score and double product. There were no systemic adverse effects or coronary events in either group. CONCLUSION: Oral L-carnitine is safe and moderately improves the duration of exercise and time to recovery of ST changes in patients with chronic stable angina.

Therapy of metabolic disorders with intravenous (IV) access ports and long term intravenous L-carnitine therapy.

With the expansion of newborn screening to include many organic acidurias and fatty acid oxidation defects, effective therapies of these disorders will be needed. Currently severe disorders such as methylmalonic and propionic aciduria. conventional therapy with diet and oral L-camitine often prove ineffective in preventing failure to thrive and recurrent metabolic decompensations. L-carnitine provides a natural pathway for removal of the toxic metabolites in these disorders and is life saving therapy but, with poor oral absorption (25%), it is difficult to supply adequate carnitine to meet the metabolic needs of these patients. Long term intravenous L-carnitine therapy, administered through a subcutaneous venous access port in 5 patients with organic acidurias [propionic aciduria (2), methylmalonic aciduria (2), 3 methylglutaconic aciduria(1)] resulted in improved growth, lower frequency of metabolic decompensations and increased tolerance of natural protein in the diet. An added benefit was the ability to initiate fluid. electrolytes, and antibiotics during metabolic decompensations at home thus averting hospitalizations.

Efeto hepato-protector de la L-carnitina en ratas sometidas a un ayuno parcial / Effect of hepato-protector of L-carnitine in rats after undergoing a portial fast

Se realizó un estudió ultraestructural y bioquímico sobre los cambios que ocurren en hígado de ratas, así como el efecto de la administración de L y D-cartinina (100 mg/kg/día), despues de ser sometidos a un ayuno parcial, se encontró que las alteraciones afectan principalmente a las mitocondrias, y al retículo endoplasmático rugoso. En las ratas tratadas con L-cartinina, las mitocondrias y el retículo endosplasmático rugoso conservaron la forma y disposición de las muestras controles. En los animales tratados con D-cartinina las alteraciones en el hepatocito fueron drásticas. Los resultados bioquímicos mostraron que los animales que recibieron L-cartinina durante el ayuno, mantuvieron valores de acidos grasos, ATP y L-cartinina muy similares a las muestras controles. Nuestros resultados sugieren que la L-cartinina ejerce un efecto hepatoprotector

L-carnitine in children with idiopathic dilated cardiomyopathy.

L-carnitine has been used in dilated cardiomyopathy secondary to carnitine deficiency in children, with favourable results. There are no reports on the effects of L-carnitine in children with idiopathic dilated cardiomyopathy. We undertook a prospective study to evaluate the effects of L-carnitine in children with idiopathic dilated cardiomyopathy. Thirteen children, mean age 3.29 +/- 1.44 years, with idiopathic dilated cardiomyopathy underwent echocardiographic evaluation while on conventional treatment alone, and with additional L-carnitine (50 mg/kg/day). To obviate the effects of spontaneous improvement, eight patients (Group 1) were restudied three weeks after stopping the drug, and five (Group 2) were restudied three weeks after addition of carnitine. Conventional treatment was continued throughout. After repeat echocardiographic examination, the parameters were compared statistically. With addition of carnitine, besides symptomatic improvement, the mean left ventricular ejection fraction improved from 36.9 +/- 16.1 percent to 46.9 +/- 14.5 percent (p < 0.001) and the mean pre-ejection period/left ventricular ejection time ratio from 39.07 +/- 14.8 to 43.2 +/- 8.1 (p < 0.01) in the entire group. These changes were concordant in both the subgroups. It was concluded that L-carnitine therapy in children with idiopathic dilated cardiomyopathy led to modest improvement in left ventricular function.

Efecto de la D-Carnitina sobre la arquitectura ventricular de corazón de embrión de pollo: estudio estructural y ultraestructural / Effects of D-Carnitine in the myoarchitecture of the chick embryo heart ventricular region

Objetivo:El presente trabajo estudia, a nivel estructural y ultraestructural, el efecto de D-carnitina sobre la arquitectura ventricular de corazón de embrión de pollo de 5 días de desarrollo .Métodos: Se disecaron corazones a partir de embriones de cinco díasde desarrollo tratados con D-carnitina (6mg./Kg. de peso). Los controles fueron obtenidos a partir de embriones tratados con solución salina isotónica. Las muestras controles y tratadas fueron fijadas, post-fijadas, deshidratadas, infiltradas, incluidas y polimerizadas. Para el análisis en microscopia de luz (ML), se realizaron cortes gruesos teñidos con azul detoluidina y para microscopia electrónica de transmisión (MET)cortes finos contrastados con acetato de uranilo y citrato de plomo. Para microscopia electrónica de barrido (MEB), las muestras , fueron desecadas y cubiertas con oro para ser observadas en un microscopio de barrido (Hitachi-300) a 20 Kvolt de aceleración. Resultados:En los corazones tratados con D-carnitina disminuye:el espacio subepicárdico, el grosor del miocardio ventricular y del septum interventricular primitivo. La región ventricular carece de apariencia cónica, pierde la estrechez caudal y el ápice exhibe un patrón trabecular homogéneo. Se observa una arquitectura ventricular de apariencia esponjosa. Resalta la infiltración grasa ó presencia de gotas de lípidos en el interior de los miocitos. Conclusiones:D-carnitina cambia el patrón de estructuración normal del corazón embrionario. Se sugiere que L-carnitina actúa como factor regulador de la relación existente entre la anatomía y el metabolismo cardíaco