The in vivo effect of L-arginine on skin elasticity in mice

ABSTRACT The human skin aging process is a complex mechanism that can be induced both by intrinsic and extrinsic factors. Observations include a decrease in the biosynthetic and proliferative capacity of cells, increased expression of matrix metalloproteinases, reduction in collagen type I expression, and the progressive disappearance of elastic tissue in the papillary dermis. L-arginine, the substrate of nitric oxide synthesis, is involved in angiogenesis and cell proliferation, as well as an indirect precursor of collagen synthesis via the proline pathway. The aim of this study was to examine the tensile strength, histology, and immunohistochemistry of female and male mice skin receiving different concentrations of topically applied L-arginine, in order to evaluate the possibility of using L-arginine as an active cosmetic ingredient in antiaging products. The results suggest that the application of L-arginine improves the mechanical resistance of skin from older female mice (20 weeks old) and promotes the formation of a larger amount of collagen and elastic fibers in the skin when applied at a concentration of 15%.

Arginine enzymatic deprivation and diet restriction for cancer treatment

ABSTRACT Recent findings in amino acid metabolism and the differences between normal, healthy cells and neoplastic cells have revealed that targeting single amino acid metabolic enzymes in cancer therapy is a promising strategy for the development of novel therapeutic agents. Arginine is derived from dietary protein intake, body protein breakdown, or endogenous de novo arginine production and several studies have revealed disturbances in its synthesis and metabolism which could enhance or inhibit tumor cell growth. Consequently, there has been an increased interest in the arginine-depleting enzymes and dietary deprivation of arginine and its precursors as a potential antineoplastic therapy. This review outlines the most recent advances in targeting arginine metabolic pathways in cancer therapy and the different chemo- and radio-therapeutic approaches to be co-applied.

Influence of phenolic compounds on the growth and arginine deiminase system in a wine lactic acid bacterium

The influence of seven phenolic compounds, normally present in wine, on the growth and arginine deiminase system (ADI) of Lactobacillus hilgardii X1B, a wine lactic acid bacterium, was established. This system provides energy for bacterial growth and produces citrulline that reacts with ethanol forming the carcinogen ethyl carbamate (EC), found in some wines. The influence of phenolic compounds on bacterial growth was compound dependent. Growth and final pH values increased in presence of arginine. Arginine consumption decreased in presence of protocatechuic and gallic acids (31 and 17%, respectively) and increased in presence of quercetin, rutin, catechin and the caffeic and vanillic phenolic acids (between 10 and 13%, respectively). ADI enzyme activities varied in presence of phenolic compounds. Rutin, quercetin and caffeic and vanillic acids stimulated the enzyme arginine deiminase about 37-40%. Amounts of 200 mg/L gallic and protocatechuic acids inhibited the arginine deiminase enzyme between 53 and 100%, respectively. Ornithine transcarbamylase activity was not modified at all concentrations of phenolic compounds. As gallic and protocatechuic acids inhibited the arginine deiminase enzyme that produces citrulline, precursor of EC, these results are important considering the formation of toxic compounds.

L-arginine, a nitric oxide precursor, reduces dapsone-induced methemoglobinemia in rats

Dapsone use is frequently associated to hematological side effects such as methemoglobinemia and hemolytic anemia, which are related to N-hydroxylation mediated by the P450 enzyme system. The aim of the present study was to evaluate the influence of L-arginine supplementation, a precursor for the synthesis of nitric oxide, as single or multiple dose regimens on dapsone-induced methemoglobinemia. Male Wistar rats were treated with L-arginine at 5, 15, 30, 60 and 180 mg/kg doses (p.o., gavage) in single or multiple dose regimens 2 hours prior to dapsone administration (40 mg/kg, i.p.). The effect of the nitric oxide synthase inhibitor L-NAME was investigated by treatment with multiple doses of 30 mg/kg (p.o., gavage) 2 hours before dapsone administration. Blood samples were collected 2 hours after dapsone administration. Erythrocytic methemoglobin levels were assayed by spectrophotometry. The results showed that multiple dose supplementations with 5 and 15 mg/kg L-arginine reduced dapsone-induced methemoglobin levels. This effect is mediated by nitric oxide formation, since the reduction in methemoglobin levels by L-arginine is blocked by simultaneous administration with L-NAME, a nitric oxide synthase inhibitor.

O uso da dapsona é frequentemente associado a efeitos adversos hematológicos, como a metemoglobinemia e anemia hemolítica, ambos relacionados com a N-hidroxilação mediada pelo sistema P450. O objetivo do estudo foi avaliar a influência da suplementação de L-arginina, um precursor da síntese de óxido nítrico, administrado em regime de dose única ou múltipla na metemoglobinemia induzida pela dapsona. Ratos machos Wistar foram tratados com L-arginina (po, gavagem) em dose única ou múltipla de 5, 15, 30, 60 e 180 mg/kg 2 horas antes da administração de dapsona (40 mg/kg, ip). O efeito do L-NAME, um inibidor de óxido nítrico sintase (NOS), foi avaliado através do tratamento com doses múltiplas de 30 mg/kg. Amostras de sangue foram coletadas duas horas após a administração de dapsona. A concentração de metemoglobina eritrocitária foi analisada por espectrofotometria. Os resultados mostraram que a suplementação em dose múltipla de 5 e 15 mg/kg de L-arginina reduziu os níveis de metemoglobina induzida pela dapsona. Este efeito é mediado pela formação de óxido nítrico, uma vez que a redução nos níveis de metemoglobina pela L-arginina é bloqueada pela administração simultânea de L-NAME, um inibidor da óxido nítrico sintase.

Arginine and glutamate levels in the gingival crevicular fluid from patients with chronic periodontitis

The objectives of this study were to determine arginine and glutamate levels in the gingival crevicular fluid (GCF) of adult chronic periodontitis patients versus periodontally healthy controls, and to compare two kinds of microdialysis probes: normal and U-shaped probes. The analysis of GCF components was developed to improve the diagnosis of periodontal disease (PD). Proteolysis in the periodontal tissues increases the concentration of amino acids (aa) in the GCF and the levels of these aa may reveal PD features and stages. GCF samples were collected by microdialysis in situ from 5 periodontally affected sites (probing depth >5 mm, clinical attachment loss >3 mm) in 14 adult chronic periodontitis patients and from 14 adult periodontally healthy controls. Capillary zone electrophoresis coupled to laser induced fluorescence detection was used to measure concentration of arginine and glutamate in the GCF. Data were analyzed statistically by ANOVA and Tukey's post-hoc tests (?=0.05). Arginine concentration was increased (p<0.001) and glutamate concentration was decreased (p<0.001) in chronic periodontitis patients as compared to controls. There were no significant differences (p=0.069) between the normal and U-shaped probes. In conclusion, the increase of arginine and decrease of glutamate concentration in GCF were associated to the presence of periodontitis, and might be used as markers to recognize periodontally susceptible subjects as well as to evaluate the treatment course.

Os objetivos deste estudo foram determinar os níveis de arginina e glutamato no fluido gengival crevicular (FGC) em pacientes com periodontite crônica contra controles saudáveis e comparar dois tipos de cânulas de microdiálise: normais e em forma de U. A análise dos componentes do FGC desenvolveu-se para melhorar o diagnóstico da doença periodontal (DP). A proteólise dos tecidos periodontais aumenta a concentração de aminoácidos (aa) no FGC e os níveis destes aa podem revelar as características e estágios da DP. Amostras de FGC foram obtidas pela técnica de microdiálise in situ de cinco zonas com o periodonto afetado (profundidade de sondagem >5 mm, perda da inserção clínica >3 mm) em 14 pacientes adultos com periodontite crônica e 14 controles saudáveis. Para medir a concentração de arginina e glutamato no GFC, usou-se a técnica de eletroforese capilar com detecção de fluorescência induzida por laser. Nos pacientes com periodontite crônica, a concentração de arginina aumentou significantemente (p<0.001), enquanto a de glutamato diminuiu significantemente (p<0.001) em comparação aos controles. Não houve diferenças significantes (p=0.069) entre as cânulas normais e as cânulas em forma de U. Conclui-se que o aumento da concentração de arginina e diminuição de glutamato no FGC estavam associados à presença de periodontite, e podem ser usados como marcadores para identificar pacientes suscetíveis à periodontite bem como avaliar a evolução do tratamento.

Effects of arginine on the survival of young rats with Walker 256 solid tumor / Efeitos da arginina na sobrevivência de ratos jovens com tumor sólido de Walker 256 / Efectos de la arginina sobre la supervivencia de las ratas jóvenes con Walker 256 tumores sólidos

A suplementação com arginina nos pacientes com câncer tem sido muito investigada nos últimos anos. Atualmente, estima-se que a suplementação dietética com este aminoácido tem melhorado a resposta imunológica, bioquímica e hematológica, reduzindo a incidência de metástases, além de incrementar o estado nutricional em investigações com animais ou seres humanos. O objetivo é avaliar o efeito da L-arginina a 8% no tempo de sobrevivência de ratos jovens com tumor sólido de Walker 256. O estudo é experimental, randomizado, duplo-cego. Os ratos receberam quatro inoculações (multilobular) na região dor lombar, totalizando 5 x 10 elevado à 6ª potência células tumorais por sítio. Os animais foram divididos em três grupos. o primeiro grupo, placebo, recebeu água por gavagem sete dias antes da inoculação tumoral, o segundo, L-arginina a 8%, iniciada quarenta e oito horas após a inoculação tumoral, e o terceiro, L-arginina a 8%, começada sete dias antes da inoculação tumoral. Analisando as curvas de sobrevida dos três grupos pelo método de Kaplan-Meir, obteve-se o seguinte resultado no vigésimo dia: a) a probabilidade de que ratos provenientes do grupo que recebeu arginina 7 dias antes da inoculação do tumor sobrevivam após o vigésimo dia de inoculação foi de 42,5%, p= 0,0001; b) os ratos pertencentes ao grupo que recebeu arginina 48 horas depois da inoculação apresentaram uma porcentagem de 27,5% em sua sobrevida após o vigésimo dia de inoculação, p= 0,0001; c) nos animais do grupo placebo, a probabilidade de sobrevivência após o vigésimo dia foi nula (p=0,0001). Os resultados sugerem que o grupo que recebeu a suplementação com L-arginina a 8%, 48 horas após a inoculação tumoral, apresentou resultados benéficos. Porém, aquele que recebeu a arginina no período de sete dias antes da inoculação tumoral foi o que obteve maior tempo de sobrevivência, sugerindo que ela possa exercer importante função para minimizar as perdas metabólicas do câncer.

Arginine supplementation in patients with cancer has been much investigated in recent years. Currently, it is estimated that dietary supplementation with this amino acid has improved the immunological response, biochemical and hematological parameters, reducing the incidence of metastases, besides increasing the nutritional status in studies with animals or humans. The objective is to evaluate the effect of L-arginine to 8% in survival time of young rats with Walker 256 solid tumor. The study is experimental, randomized, double-blind study. the rats received four inoculations (multilobular) in the low back pain, amounting to 5 x 10 to the 6th power tumor cells per site. The animals were divided into three groups. The first group, placebo, received water by gavage seven days before the tumor inoculation, the second, L-arginine to 8%, starting forty-eight hours after tumor inoculation, and the third, L-arginine to 8%, started seven days before tumor inoculation. Analyzing the survival curves of the three groups by the Kaplan-Meir, we obtained the following result on the twentieth day: a) the likelihood that rats from the group that received arginine 7 days before inoculation of the tumor to survive after the twentieth day inoculation was 42.5%, p = 0.0001, b) mice in the group that received arginine 48 hours after inoculation showed a percentage of 27.5% in its survival after the twentieth day of inoculation, p = 0.0001, c) the animals in the placebo group, the probability of survival after the twentieth day was zero (p = 0.0001). The results suggest that the group that received suplemetação with L-arginine to 8%, 48 hours after tumor inoculation, showed beneficial results. But he who received the arginine within seven days before tumor inoculation was the one that had a longer survival, suggesting that it may play an important role to minimize loss of metabolic cancer.

Suplementos de arginina en pacientes con cáncer ha sido muy investigado en los últimos años. En la actualidad, se estima que los suplementos de la dieta con este aminoácido se ha mejorado la respuesta inmunitaria, parámetros bioquímicos y hematológicos, la reducción de la incidencia de metástasis, además de mejorar el estado nutricional en los estudios con animales o seres humanos. El objetivo es evaluar el efecto de la L-arginina y el 8% del tiempo de supervivencia de las ratas jóvenes con Walker 256 de tumores sólidos. El estudio es experimental, aleatorizado, doble ciego. las ratas recibió cuatro vacunas (multinodular) en el dolor de espalda baja, por valor de 5 x 10 a las células tumorales sexta potencia por sitio. Los animales fueron divididos en tres grupos. El primer grupo, placebo recibieron agua por sonda siete días antes de la inoculación del tumor, el segundo, la L-arginina a 8%, a partir de cuarenta y ocho horas después de la inoculación del tumor, y la tercera, la L-arginina a 8%, comenzó a siete días antes de la inoculación del tumor. El análisis de las curvas de supervivencia de los tres grupos por el método de Kaplan-Meier, se obtuvo el siguiente resultado a los veinte días: a) la probabilidad de que las ratas del grupo que recibió arginina 7 días antes de la inoculación del tumor de sobrevivir después de los veinte días inoculación fue del 42,5%, p = 0,0001, b) los ratones en el grupo que recibió la arginina 48 horas después de la inoculación mostraron un porcentaje de 27,5% en la supervivencia después de los veinte días de la inoculación, p = 0.0001, c) los animales en el grupo placebo, la probabilidad de supervivencia después de los veinte días fue de cero (p = 0,0001). Los resultados sugieren que el grupo que recibió suplemetação con L-arginina a 8%, 48 horas después de la inoculación del tumor, mostró resultados beneficiosos...

Lysine: arginine ratio of a protein influences cholesterol metabolism. Part 1--Studies on sesame protein having low lysine: arginine ratio.

The effect of globulin fraction with a lysine: arginine (lys:arg) ratio 0.67, isolated from sesame (Sesamum Indicum) seeds on cholesterol metabolism was studied in rats fed cholesterol free and cholesterol containing diet and compared with casein (lys:arg ratio-2.0). Rats fed sesame seed globulin showed significantly lower concentrations of cholesterol in the serum and aorta. The decrease in serum was manifested in both HDL and LDL + VLDL fractions. There was increased cholesterogenesis in the liver as was evident from increased incorporation of labeled acetate into cholesterol and increased activity of 3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. Increased hepatic diversion of cholesterol to bile acid synthesis and increased fecal excretion of bile acids and sterols were also observed in rats fed sesame seed globulins. Rats fed sesame globulins also showed significantly higher activity of lipoprotein lipase in the heart and adipose tissue and that of plasma Lecithin: cholesterol acyltransferase (LCAT). These studies suggest that low lysine: arginine ratios of a protein exert hypocholesterolemic effects.

Exaggerated Bezold-Jarisch reflex in the hypertension induced by inhibition of nitric oxide synthesis

The present study was designed investigate the role of cardio-pulmonary reflex, more specifically the bezold-Jarisch reflex, in experimental hypertension induced by chronic administration of Nw-nitro-L-arginine methyl ester (L-NAME) (0,5 mg/ml) added to the drinking water for 6 days. The study was perfomed in male Wistar rats (200-350 g), 9 animals per group. L-NAME ingestion caused a significant increase in resting mean arterial pressure (MAP: 182 + or - 4mmHg) and heart rate (HR: 447 = or - 20 bpm) when compared to untreated rats (MAP: 112 = or - 3 mmHg and HR: 355 + or - 10 bpm). Cardiopulmonary receptors were chemically stimulated with bolus injections of 5-hydroxytryptamine (5-HT, 4-10 ug/Kg, iv) followed by measuring the falls in diastolic arterial pressure (DAP) and HR in conscious and freely moving animals. An expected, the responses to intravenous injections of 5-HT consisted of a dose-dependent reduction in HR (from 26 = or - 14 to 175 + or - 25 bpm) and DAP (from 7 + or - 4 to 39 + or - 3 mmHg) in the control rats. Both bradycardia and diastolic hypotension were significantly accentuated in the L-NAME animals (approximately 30 per cent). These data suggest that, in contrast to other models of hypertension, in the present one caused by inhibition of nitric oxide synthesis, the Bezold-Jarisch reflex exaggerated. This neural dysfunction could be related to changes in the cardiac vagal effrent or effector

Efecto de L-arginina y poliaminas sobre la movilidad espermática / Effect of L-arginine and polyamines on spermatic motility

En este trabajo se destaca la importancia bioquímica y fisiológica en el sistema reproductor masculino de L-arginina, ya que este aminoácido ha sido utilizado con éxito en el tratamiento de algunos problemas de fertilidad. Este aminoácido está relacionado con el metabolismo de las poliaminas putrecinas, espermidina y espermina, moléculas que tienen importancia fisiológica, ya que se ha sugerido su participación como iniciadoras del proceso de movilidad espermática. Se sugieren algunas aplicaciones prácticas de la L-arginina.