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.

Follicular fluid from infertile women with mild endometriosis impairs in vitro bovine embryo development: potential role of oxidative stress / Fluido folicular de mulheres inférteis com endometriose leve prejudica o desenvolvimento in vitro de embriões bovinos: Potencial papel do estresse oxidativo

Abstract Objective To investigate whether follicular fluid (FF) from infertile women with mild endometriosis (ME) alters in vitro bovine embryo development, and whether the antioxidants N-acetyl-cysteine (NAC) and/or L-carnitine (LC) could prevent such damages. Methods Follicular fluid was obtained from infertile women (11 with ME and 11 control). Bovine oocytes were matured in vitro divided in: No-FF, with 1% of FF from control women (CFF) or ME women (MEFF); with 1.5mM NAC (CFF + NAC, MEFF + NAC), with 0.6mg/mL LC (CFF + LC, MEFF + LC), or both antioxidants (CFF + NAC + LC, MEFF + NAC + LC). After in vitro fertilization, in vitro embryo culture was performed for 9 days. Results A total of 883 presumptive zygotes were cultured in vitro. No differences were observed in cleavage rate (p = 0.5376) and blastocyst formation rate (p = 0.4249). However, the MEFF group (12.5%) had lower hatching rate than the No-FF (42.1%, p = 0.029) and CFF (42.9%, p = 0.036) groups. Addition of antioxidants in the group with CFF did not alter hatching rate (p ≥ 0.56), and in groups with MEFF, just NAC increased the hatching rate [(MEFF: 12.5% versus MEFF + NAC: 44.4% (p = 0.02); vs MEFF + LC: 18.8% (p = 0.79); versus MEFF + NAC + LC: 30.8% (p = 0.22)]. Conclusion Therefore, FF from infertile women with ME added to medium of in vitro maturation of bovine oocytes impairs hatching rate, and NAC prevented these damages, suggesting involvement of oxidative stress in worst of oocyte and embryo quality of women with ME.

Resumo Objetivo Investigar se o fluido folicular (FF) de mulheres inférteis com endometriose leve (ME, na sigla eminglês) altera o desenvolvimento in vitro de embriões bovinos, e se os antioxidantes N-acetil-cisteína (NAC) e/ou L-carnitina (LC) poderiam prevenir possíveis danos. Métodos O FF foi obtido de mulheres inférteis (11 com ME e 11 controles). Oócitos bovinos foram maturados in vitro divididos em: sem FF (No-FF), com 1% de FF de mulheres controle (CFF) ou mulheres comME (MEFF); com 1,5mMde NAC (CFF + NAC, MEFF + NAC), com 0,6mg/mL de LC (CFF + LC, MEFF + LC), ou ambos antioxidantes (CFF + NAC + LC, MEFF + NAC + LC). Depois da fertilização in vitro, o cultivo in vitro de embriões foi realizado por 9 dias. Resultados Um total de 883 zigotos presumidos foram cultivados in vitro. Nenhuma diferença foi observada na taxa de clivagem (p = 0,5376) e na taxa de formação de blastocistos (p = 0,4249). Entretanto, o grupo MEFF (12.5%) teve menor taxa de eclosão de blastocistos do que os grupos No-FF (42,1%, p = 0,029) e CFF (42,9%, p = 0,036). Adição de antioxidantes no grupo comCFF não alterou a taxa de eclosão (p ≥ 0.56), e nos grupos com MEFF, somente a NAC aumentou a taxa de eclosão [(MEFF: 12.5% versus MEFF + NAC: 44.4% (p = 0.02); versus MEFF + LC: 18.8% (p = 0.79); versus MEFF + NAC + LC: 30.8% (p = 0.22)]. Conclusão Portanto, o FF de mulheres inférteis com ME adicionado ao meio de maturação in vitro de oócitos bovinos prejudica a taxa de closão embrionária, e a NAC preveniu esses danos, sugerindo o envolvimento do estresse oxidativo na piora da qualidade oocitária e embrionária de mulheres com ME.

L-carnitine supplementation descreases hepatic triglyceride accumulation in Holstein cows during the transition period / La suplementación con L-carnitina disminuye la acumulación de triglicéridos hepáticos en vacas Holstein durante el periodo de transición / Suplementação com L-carnitina diminui o acúmulo de triglicerídeos hepáticos em vacas Holandesas durante o período de transição

Abstract Background: The increased use of body reserves observed during peripartum leads to higher needs of L-carnitine by cows, which is restrictive under the production conditions of Colombian high tropics. Objective: To evaluate the lipotropic potential of L-carnitine in Holstein dairy cows during the transition period to lactation. Methods: Twenty-one Holstein cows were fed 0, 100, or 200 g/d L-carnitine fumarate from d 260 of gestation to d 20 postpartum. Hepatic triacylglycerides concentration, total carnitine, free carnitine, acylcarnitine, and serum levels of non-esterified fatty acids (NEFA), β-hydroxybutyrate (β-HB) and urea were determined by spectrophotometry. Repeated measures analysis was used to determine the effects of dose, measurement period, and their interactions. Results: Hepatic triglycerides and the different forms of carnitine showed no difference between sampling periods (p>0.05). Hepatic triglycerides concentration was low and decreased in response to 200 g/d L-carnitine fumarate supplementation (p<0.05). This decrease in hepatic triglycerides could be due to increased fatty acid oxidation. L-carnitine supplementation significantly increased (p<0.05) blood urea concentration, possibly through stimulation of the urea cycle, as previously described in other species. Conclusion: Supplementation with L-carnitine decreased the hepatic concentration of triglycerides, possibly due to increased liver oxidation of fatty acids.

Resumen Antecedentes: El incremento en la utilización de reservas corporales durante el periparto en vacas exige una alta disponibilidad de L-carnitina, la cual puede ser limitante bajo las condiciones propias de producción del trópico alto colombiano. Objetivo: Evaluar el potencial lipotrópico de la L-carnitina en vacas lecheras Holstein durante el periodo de transición a la lactancia. Métodos: Se suministraron dosis de 0, 100 y 200 g/d de fumarato de L-carnitina a 21 vacas Holstein a partir del d 260 de gestación y hasta el d 20 postparto. Se determinaron las concentraciones hepáticas de triacilglicéridos, carnitina total, carnitina libre y acil carnitina, y las concentraciones plasmáticas de ácidos grasos no esterificados (NEFA), β-hidroxibutirato (β-HB) y urea. Un análisis de medidas repetidas fue usado para determinar los efectos de la dosis, el periodo de medición, y sus interacciones. Resultados: Las concentraciones hepáticas de triglicéridos y de las diferentes formas de carnitina no difirieron significativamente (p>0,05) entre periodos de muestreo. La concentración hepática de triglicéridos fue baja, y mostró una disminución significativa (p<0,05) en respuesta a la suplementación con 200 g/d de fumarato de L-carnitina. La disminución en los triglicéridos hepáticos podría deberse a un aumento en la oxidación de ácidos grasos. La suplementación con L-carnitina aumentó significativamente (p<0,05) la concentración de urea en sangre, posiblemente a través de un mecanismo de estimulación del ciclo de la urea, descrito previamente en otras especies. Conclusión: La suplementación con L-carnitina disminuyó la concentración hepatica de trigliceridos, debido posiblemente a un aumento en la oxidación de ácidos grasos en hígado.

Resumo Antecedentes: O aumento do uso de reservas corporais durante o periparto requer alta disponibilidade de L-carnitina, que pode ser limitante nas condições de produção no trópico alto colombiano. Objetivo: Avaliar o potencial lipotrópico da L-carnitina em vacas leiteiras Holstein durante o período de transição para a lactação. Métodos: Quantidades de 0, 100 e 200 g/d de fumarato de L-carnitina foram administradas a 21 vacas holandesas durante o d 260 da gestação e até ao d 20 pós-parto. Foram determinadas as concentrações hepáticas de triacilglicerídeos, carnitina total, carnitina livre e acil carnitina e as concentrações plasmáticas de ácidos graxos não esterificados (NEFA), β-hidroxibutirato (β-HB) e ureia. Uma análise das medidas repetidas foi usada para determinar os efeitos da dose, período de medição e suas interações. Resultados: As concentrações hepáticas de triglicerídeos e as diferentes formas de carnitina não diferiram significativamente entre os períodos de amostragem (p>0,05). A concentração hepática de triglicerídeos foi baixa e mostrou diminuição significativa (p<0,05) em resposta à suplementação com 200 g/d de fumarato de L-carnitina. A diminuição dos triglicerídeos hepáticos pode ser devido a um aumento na oxidação de ácidos graxos. A suplementação com L-carnitina aumentou significativamente (p<0,05) a concentração de ureia no sangue, possivelmente através de um mecanismo de estimulação do ciclo da ureia previamente descrito em outras espécies. Conclusão: A suplementação com L-carnitina diminuiu a concentração hepática de triglicerídeos, possivelmente devido ao aumento da oxidação de ácidos graxos no fígado.

Effects of L-carnitine supplementation on ascites syndrome in the broilers grown at high altitude / Efectos síndrome de la suplementación con L-carnitina en el de ascitis en los pollos de engorde criados a gran altura

ABSTRACT Objective. Investigate the effects of L-carnitine as a potential means of reducing the incidence of ascites in broilers and its relationship with physiological and biochemical paramaters. Material and methods. One-day-old 300 male broiler chicks (Ross 308) were used in the trial. The group without L-carnitine supplementation (0) was assigned as control and the groups that received 100, 150, 200 and 250 mg/L L-carnitine supplementation in water were assigned as treatment groups. The trial was completed in 35 days. Results. L-carnitine supplementation did not have any significant effect on live weight gain, feed consumption, water consumption and feed conversion ratio. Levels of blood plasma and hemogram parameters HDL, Triglyceride, CK, RBC and MCH were significantly affected by L-carnitine (p<0.05). Blood gas parameter pH value was significantly affected by L-carnitine supplementation in the broilers with ascites. Blood gas pH value significantly increased with 100 mg/L L-carnitine supplementation compared to that of control (p<0.05). While blood pH was 7.21 in the animals with ascites, it was determined as 7.48 in healthy animals. Concentrations of SO2 and ctO2 were higher in healthy animals, while ctCO2P and hemoglobin concentrations were higher in ascitic animals (p<0.05). Conclusions. Ascites mortality rates starting from the control group were calculated respectively as %; 20.00, 18.33, 26.67, 28.33 and 28.33%. 76.71% of total ascites deaths were in the 5th week. It was concluded that low doses of L-carnitine supplementation may have positive effects in the broilers grown at high altitude.

RESUMEN Objetivo. Investigar los efectos de la L-carnitina como un medio potencial para reducir la incidencia de ascitis en pollos de engorde y su relación con parámetros fisiológicos y bioquímicos. Material y métodos. Se utilizaron 300 pollos de engorde machos de un día de edad (Ross 308) en el ensayo. El grupo sin suplementación de L-carnitina (0) se asignó como control y los grupos que recibieron suplementos de 100, 150, 200 y 250 mg/L de L-carnitina en agua se asignaron como grupos de tratamiento. La prueba se completó en 35 días. Resultados. La suplementación de L-carnitina no tuvo ningún efecto significativo sobre el aumento de peso vivo, consumo de alimento, consumo de agua y tasa de conversión alimenticia. Los niveles de plasma sanguíneo y los parámetros del hemograma HDL, triglicéridos, CK RBC y MCH se vieron afectados significativamente por L-carnitina (p<0.05). El valor del pH del parámetro del gas en sangre se vio significativamente afectado por la suplementación con L-carnitina en los pollos de engorde con ascitis. El valor del pH del gas en la sangre aumentó significativamente con la suplementación de 100 mg/L de L-carnitina en comparación con la del control (p<0.05). Mientras que el pH de la sangre fue de 7.21 en los animales con ascitis, se determinó como 7.48 en animales sanos. Las concentraciones de SO2 y ctO2 fueron mayores en animales sanos, mientras que las concentraciones de ctCO2P y hemoglobina fueron mayores en animales ascíticos (p<0.05). Conclusiones. Las tasas de mortalidad por ascitis a partir del grupo control se calcularon respectivamente como %; 20.00, 18.33, 26.67 y 28.33. 76.71% de las muertes totales de ascitis fueron en la quinta semana. Se concluyó que dosis bajas de suplementos de L-carnitina pueden tener efectos positivos en los pollos de engorde criados a gran altitude.

Hiperamonemia en niños: clasificación y opciones terapéuticas / Hyperammonaemia in children: classification and therapeutic options

La hiperamonemia se presenta en forma secundaria por aumento en la producción de amonio, como en la hemorragia gastrointestinal o disminución de la eliminación, como ocurre en errores innatos del metabolismo, principalmente en aquellos con defectos en el ciclo de la urea, insuficiencia hepática o fármacos. Clasificar la hiperamonemia y reportar las opciones terapéuticas en niños, su abordaje clínico y revisión de la literatura. Estudio prospectivo, descriptivo y transversal de niños con hiperamonemia. Variables: edad, género, etiología, niveles de amonio, clínica, tratamiento. 21 pacientes, 12 (57,12%) varones y 9 (42,88%) hembras. Edad promedio 3,91 años (rango:<1mes-14 años). Amonio promedio general 214,66 mmol/l (rango:110-980), clasificados según severidad: sin insuficiencia hepática 11/21 con promedio de amonio 99,44 y 201 mmol/l en hiperamonemia leve y moderada respectivamente. Clínica y laboratorio de insuficiencia hepática en 10/21 con promedio de amonio de 114,44, 287,51 y 756,66 en leve, moderada y severa hiperamonemia, con una diferencia significativa entre el nivel de amonio y la presencia o ausencia de insuficiencia hepática (p<0,0001); 5/10 con insuficiencia hepática ingresaron a terapia intensiva, 4 de ellos presentaron encefalopatía hepática, un paciente fallecido. Etiología: Error innato del metabolismo 33,33%, toxicidad por medicamentos 23,80%, hepatitis viral A fulminante 19,04% y otros virus 9,52%, hepatitis autoinmune 4,76% y urosepsis 4,76%. En los casos leves-moderados se administró lactulosa dosis respuesta vía oral 19/21 y por enema rectal 7/21 con L-carnitina en 15/21 y en Hiperamonemia severa adicionalmente Benzoato de sodio en 4/21 y hubo indicación de hemodiálisis en 3 pacientes. Restricción proteica en todos, vitaminoterapia y 6 niños tratados con ácido ursodeoxicólico. La hiperamonemia es multifactorial, requiere diagnóstico temprano, la clasificación de severidad permite el tratamiento oportuno para evitar complicaciones....

Hyperammonaemia occurs secondarily by increased production of ammonia, as gastrointestinal bleeding or decreased elimination, as occurs in inborn errors of metabolism, especially in those with defects in the urea cycle, liver failure or drugs. To classify the report hyperammonaemia and therapeutic options in children, its clinical approach and review of the literature. Prospective, descriptive and transversal children with hyperammonaemia. Variables: age, gender, etiology, ammonia levels, clinical treatment. 21 patients, 12 (57,12%) males and 9 (42,88%) females. Mean age 3,91 years (range: <1m-14a). ammonium 214,66 mmol / l (range :110-980), classified according to severity: no hepatic impairment 11/21 with 99,44 average ammonium and 201 mmol / l in Hyperammoanemia mild and moderate respectively. Clinical and laboratory liver failure 10/21 with ammonium averaging 114,44, 287,51 and 756,66 as mild, moderate and severe hyperammonemia, with a significant difference between the level of ammonia and the presence or absence of liver failure (p < 0,0001), 5/10 with liver failure admitted to intensive care, 4 of them had hepatic encephalopathy, a patient died. Etiology: An inborn error of metabolism 33,33%, 23,80% drug toxicity, fulminant viral hepatitis and other viruses 19,04% 9,52% 4,76% autoimmune hepatitis and urosepsis 4,76%. In mild-moderate cases were given oral lactulose Dose 19/21 and by enema rectal 7/21 with L-carnitine in 15/21 and further severe Hyperammonemia sodium benzoate 4/21 and was indication of hemodialysis in 3 patients. Protein restriction at all, vitamin therapy and 6 children treated with ácidoursodeoxicólico. Hyperammonemia is multifactorial, requires early diagnosis, classification of severity allows early treatment to avoid complications and development of irreversible neurological sequelae

Urinary excretion of L-carnitine, acetyl-L-carnitine, propionyl-L-carnitine and their antioxidant activities after single dose administration of L-carnitine in healthy subjects

The urine excretion of L-carnitine (LC), acetyl-L-carnitine (ALC) and propionyl-Lcarnitine (PLC) and their relations with the antioxidant activities are presently unknown. Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Urine concentrations of LC, ALC and PLC were detected by HPLC. Superoxide dismutase (SOD), total antioxidative capacity (T-AOC), malondialdehyde (MDA) and nitrogen monoxidum (NO) activities were measured by spectrophotometric methods. The 0~2 h, 2~4 h, 4~8 h, 8~12 h, 12~24 h excretion of LC was 53.13±31.36 µmol, 166.93±76.87 µmol, 219.92±76.30 µmol, 100.48±23.89 µmol, 72.07±25.77 µmol, respectively. The excretion of ALC was 29.70±14.43 µmol, 80.59±32.70 µmol, 109.85±49.21 µmol, 58.65±18.55 µmol, and 80.43±35.44 µmol, respectively. The urine concentration of PLC was 6.63±4.50 µmol, 15.33±12.59 µmol, 15.46±6.26 µmol, 13.41±11.66 µmol and 9.67±7.92 µmol, respectively. The accumulated excretion rate of LC was 6.1% within 24h after its administration. There was also an increase in urine concentrations of SOD and T-AOC, and a decrease in NO and MDA. A positive correlation was found between urine concentrations of LC and SOD (r = 0.8277) or T-AOC (r = 0.9547), and a negative correlation was found between urine LC excretions and NO (r = -0.8575) or MDA (r = 0.7085). In conclusion, a single oral LC administration let to a gradual increase in urine L-carnitine excretion which was associated with an increase in urine antioxidant enzymes and the total antioxidant capacities. These data may be useful in designing therapeutic regimens of LC or its analogues in the future.

A excreção urinária de L-carnitina (LC), acetil-L-carnitina (ALC) e propionil-L-carnitine (PLC) e as suas relações com as atividades antioxidantes são presentemente desconhecidos. Líquido de L-carnitina (2,0 g) foi administrada por via oral como uma dose única em 12 indivíduos saudáveis. As concentrações urinárias de LC, PLC e ALC foram detectados por HPLC. Atividades superóxido dismutase (SOD), a capacidade antioxidante total (T-AOC), malondialdeído (MDA) e óxido nítrico (NO) foram medidas por métodos espectrofotométricos. O 0~2 h, 2~4 h, 4~8 h, 8~12 h, 12~24 h excreção de LC foi 53,13±31.36 µmol, 166,93±76.87 µmol, 219,92±76.30 µmol, 100,48±23.89 µmol, 72,07±25.77 µmol, respectivamente. A excreηão de ALC foi 29,70±14.43 µmol, 80,59±32.70 µmol, 109,85±49.21 µmol, 58,65±18.55 µmol, e 80,43±35.44 µmol, respectivamente. A concentraηão de urina de PLC foi 6,63±4.50 µmol, 15,33±12.59 µmol, 15,46±6.26 µmol, 13,41±11.66 µmol e 9,67±7.92 µmol, respectivamente. A taxa de excreηão acumulada de LC foi de 6,1% 24 horas após sua administração. Houve também um aumento nas concentrações de urina de SOD e T-COA e diminuição de NO e de MDA. Correlação positiva foi encontrada entre as concentrações de urina de LC e SOD (r = 0,8277) ou T-AOC (r = 0,9547) e correlação negativa entre a excreção de LC e NO (r = -0,8575) ou MDA (r = 0,7085). Em conclusão, a administração oral única de LC leva ao aumento gradual na excreção urinária de L-carnitina, que foi associada com o aumento das enzimas antioxidantes na urina e as capacidades antioxidantes totais. Estes dados podem ser úteis no futuro para o planejamento de esquemas terapêuticos de LC ou os seus análogos, no futuro.

O uso da L-carnitina como adjuvante no tratamento da miocardiopatia dilatada em criança com Aids / Usage of L-carnitine as adjuvant in the treatment of dilated cardiomyopathy in a child with Aids

OBJETIVO: Apresentar a resposta cardiovascular à L-carnitina de um paciente com insuficiência cardíaca congestiva decorrente de miocardiopatia dilatada pelo vírus da imunodeficiência humana. DESCRIÇÃO DO CASO: Criança com quadro clínico de insuficiência cardíaca congestiva grave devido à miocardiopatia dilatada pela síndrome de imunodeficiência adquirida. O tratamento para as manifestações clínicas foi instituído, com pouca resposta clínica. Com objetivo de melhorar o desempenho energético/metabólico dos cardiomiócitos, foi instituída terapia com L-carnitina. Observou-se significativa melhora clínica do paciente, em relação ao desempenho cardíaco, mesmo antes do início do tratamento com os fármacos antirretrovirais. COMENTÁRIOS: A L-carnitina é um composto que facilita o transporte dos ácidos graxos de cadeia longa para dentro da mitocôndria. Nesse caso, o uso da L-carnitina parece ser clinica e bioquimicamente justificado.

OBJECTIVE: To present the cardiovascular response to L-carnitine of a patient with congestive heart failure caused by dilated cardiomyopathy and human immunodeficiency virus. CASE DESCRIPTION: Child with a clinical history of severe congestive heart failure due to dilated cardiomyopathy caused by acquired immunodeficiency syndrome. The treatment for the symptoms resulted in a poor clinical response. In order to improve the energetic performance/metabolism of cardiomyocytes, therapy with L-carnitine was established. There was significant clinical improvement of the cardiac performance of the patient, even before starting the treatment with antiretroviral drugs. COMMENTS: L-carnitine is a compound that facilitates the transport of long-chain fatty acids into the mitochondria. In this case the administration of L-carnitine appears to be clinically and biochemical justified.

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.

Estudio del mecanismo de fosforilación de proteínas como respuesta celular hepática inducida por adriamicina, con o sin protección con L carnitina / Study of protein phosphorylation mechanism induced by adriamycin in hepatic tissue with or without L-carnitine

Los cambios en los estados de fosforilación de proteínas han sido asociados a numerosas patologías de diferentes orígenes y severidad, y estas alteraciones, pueden estar vinculadas a estrés oxidativo y modificaciones en proteínas quinasas y fosfatasas. En este sentido, la terapia con adriamicina ha sido vinculada con estrés oxidativo cardiaco y hepático con subsecuente disfunción de tales órganos. Adicionalmente, al estrés cardiaco por adriamicina, el hígado podría representar otro blanco tóxico de la droga. Sin embargo, las alteraciones hepáticas han sido pobremente estudiadas. En este trabajo se estudio el patrón de fosforilación de proteínas de tejido hepático, ante la administración de adriamicina. Ratas Sprague Dawley se distribuyeron en cuatro grupos al azar: control, adriamicina, carnitina y adriamicina carnitina. Los tratamientos administrados por via intravenosa (VI) cada tres días/3 dosis fueron: 5 mg/Kg de peso de ADR y 20mg/Kg de peso de carnitina y combinando ambos agentes. Los animales se sacrificaron, tomándose el lóbulo hepático medio para ensayos de: fosforilación con [ã 32 -P] ATP, inmunodetección de fosfoproteínas en serina y tirosina, proteína JNK y C-jun. Los patrones de fosforilación de proteínas entre los grupos fueron diferentes observándose mayor expresión de proteínas fosforiladas en los grupos adriamicina. La carnitina revierte el efecto sobre la fosforilación comportándose como hepatoprotector ante la droga.

The changes in the pattern of protein phosphorylation have been associated to numerous pathologies of differentorigins and severity; these alterations can be linked to oxidative stress and subsequent modifications in the protein kinases and phosphatases. In this regard, adriamycin therapy have been related to the heart and liver oxidative stress and organ disfunction. Therefore, in addition to the heart, the liver might be another adriamycin toxic target. However, adriamycin liver alterations have been poorly studied. The aim of this work was to determined liver protein phosphorylation before and after adriamycin administration. Female Sprague-Dawley rats (n=3), 40-60g body weight, were randomized into four groups: control, adriamycin, carnitine and adriamycin-carnitine. Saline adriamycin (15mg/Kg body weight) and carnitine (20 mg before adriamycin) were given intravenously (0,1 ml). Samples from the medium liver lobe were taken for biochemical experiments including phosphorylation with [ã 32 -P] ATP, inmunodetection of phosphoproteins in serine and tirosine, JNK and C-jun proteins. The protein phosphorylation was different between the groups studied. The greater expression of protein phosphorylates was determined in the adriamycin group. We suggest that there is a relationship between carnitine administration and decreased expression of protein phosphorylates. Carnitine may be a hepatoprotector.