Creatine and the Liver: Metabolism and Possible Interactions.

The process of creatine synthesis occurs in two steps, catalyzed by L-arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase (GAMT), which take place mainly in kidney and liver, respectively. This molecule plays an important energy/pH buffer function in tissues, and to guarantee the maintenance of its total body pool, the lost creatine must be replaced from diet or de novo synthesis. Creatine administration is known to decrease the consumption of Sadenosyl methionine and also reduce the homocysteine production in liver, diminishing fat accumulation and resulting in beneficial effects in fatty liver and non-alcoholic liver disease. Different studies have shown that creatine supplementation could supply brain energy, presenting neuroprotective effects against the encephalopathy induced by hyperammonemia in acute liver failure. Creatine is also taken by many athletes for its ergogenic properties. However, little is known about the adverse effects of creatine supplementation, which are barely described in the literature, with reports of mainly hypothetical effects arising from a small number of scientific publications. Antioxidant effects have been found in several studies, although one of the theories regarding the potential for toxicity from creatine supplementation is that it can increase oxidative stress and potentially form carcinogenic compounds.

Effect of melatonin supplementation on food and water intake in streptozotocin-diabetic and non-diabetic male Wistar rats / Efecto de la suplementación oral con melatonina sobre la ingestión de agua y alimento en ratas Wistar macho con diabetes experimental

The effect of orally supplemented melatonin (MT) at 1mg/kg bw for 4 weeks on feeding behavior of non-diabetic and diabetic male Wistar rats has been studied by computerized meal pattern analysis. Exogenous MT has asatiating effect in non-diabetic rats, but not in diabetic animals. The changes in feeding behavior induced by MT in non-diabetic animals are related to changes in meal frequency, size and duration leading to lower total food intake during the scotophase. MT administration to diabetic rats resulted in lower drinking time and higher faecaloutput, without further behavioral effects. We conclude that the notorious metabolic changes ocurring in the streptozotocin-diabetic rat can overcome most of the underlying effects of MT supplementation. The possible MT usage for therapeutical purposes could benefit from the lack of behavioral alterations in diabetic animals (AU)

Varias líneas de evidencia señalan a la melatonina (MT) como un importante factor en el complejo entramado de la regulación de la ingestión de alimento. Puesto que la secreción de MT aumenta en la rata con diabetes tipo I, y dada la importancia de MT en el tracto gastrointestinal,es interesante comprobar los efectos de MT sobre el alterado comportamiento ingestivo de estos animales.Se ha estudiado el efecto de la suplementación oral de MT(1 mg por kg de peso corporal y día) en la escotofase sobre el comportamiento ingestivo de ratas Wistar macho diabéticas y no diabéticas durante cuatro semanas mediantea nálisis de pautas de ingestión asistido por ordenador. La administración de MT exógena indujo un efecto de saciación en ratas no diabéticas, pero no en animales diabéticos.Los cambios en comportamiento ingestivo inducidos por MT en animales no diabéticos están relacionados con cambios en frecuencia, tamaño y duración de las comidas,con el resultado de una disminución de la ingestión total de alimento durante la escotofase. La administración deMT en ratas diabéticas originó una disminución deltiempo total de actividad dípsica y aumento de la masafecal durante la escotofase, sin otros cambios comportamentales significativos. Se concluye que los notables cambios metabólicos que tienen lugar en la rata con diabetes experimental inducida por estreptozotocina provocan cambios comportamentales más potentes que los ejercidos por la suplementación oral con MT. El posible uso terapéutico de MT podría beneficiarse de la falta de alteraciones comportamentales en animales diabéticos (AU)

Effect of melatonin supplementation on food and water intake in streptozotocin-diabetic and non-diabetic male Wistar rats.

The effect of orally supplemented melatonin (MT) at 1 mg/kg bw for 4 weeks on feeding behavior of non-diabetic and diabetic male Wistar rats has been studied by computerized meal pattern analysis. Exogenous MT has a satiating effect in non-diabetic rats, but not in diabetic animals. The changes in feeding behavior induced by MT in non-diabetic animals are related to changes in meal frequency, size and duration leading to lower total food intake during the scotophase. MT administration to diabetic rats resulted in lower drinking time and higher faecal output, without further behavioral effects. We conclude that the notorious metabolic changes occurring in the streptozotocin-diabetic rat can overcome most of the underlying effects of MT supplementation. The possible MT usage for therapeutical purposes could benefit from the lack of behavioral alterations in diabetic animals.

Radiomodifying effect of organic grape juice supplementation on hematological parameters and organ weight in whole-body X-irradiation in rats.

The aim of this study is testing black grape juice as a radiomodifier against whole body X-irradiation using an animal model. Sixteen male Wistar rats were divided into four groups where two were irradiated by X-rays from a 200 kV machine specially designed to biological samples. Animals were fed ad libitum and drank voluntarily 2-10 ml a day of grape juice or placebo (isocaloric glucose and fructose solution) for one week before and two weeks after 6 Gy X-irradiation when they were sacrificed. Results have shown a significant liver weight loss in irradiated placebo group only while grape juice one has presented no losses. Hematological analysis showed typical abnormalities for ionizing radiation exposure, including early leucopenia and anemia. The intake of grape juice induced an increase in granulocyte percent count.

[Glycine: a cell-protecting anti-oxidant nutrient]. / La glicina: un nutriente antioxidante protector celular.

For many researchers it is still difficult to accept that beneficial effects can be obtained in several disease states with the simplest amino acid, glycine. However, evidence is mounting in favour of this idea. It is now clear that dietary glycine protects against shock caused either by blood loss or endotoxin, reduces alcohol levels in the stomach and improves recovery from alcoholic hepatitis, diminishes liver injury caused by hepatotoxic drugs and blocks programmed cell death and reduces the nephrotoxicity caused by the drug cyclosporin A in the kidney, preventing hypoxia and free radical formation. It could be also useful in other inflammatory diseases since it diminishes cytokines production. We review some of the beneficial effects of glycine and their responsible mechanism, which could led to advice its use in the therapy of different diseases.

Dietary glycine inhibits activation of nuclear factor kappa B and prevents liver injury in hemorrhagic shock in the rat.

We investigated the effects of a glycine-containing diet (5%) on liver injury caused by hemorrhagic shock and resuscitation in rats. Anesthetized rats were bled to a mean arterial blood pressure of 35-40 mm Hg for 1 h and then resuscitated with 60% of shed blood and lactated Ringer's solution. Feeding the rats glycine significantly reduced mortality, the elevation of plasma transaminase levels and hepatic necrosis. The increase in plasma TNFalpha and nitric oxide (NO) was also blunted by glycine feeding. Hemorrhagic shock resulted in oxidative stress (significant elevations in TBARS and in the oxidized/reduced glutathione ratio) and was accompanied by a reduced activity of the antioxidant enzymes Mn- and Cu,Zn-superoxide dismutase, glutathione peroxidase and catalase, overexpression of inducible NO synthase (iNOS), and activation of nuclear factor kappa B (NF-kappaB). Glycine ameliorated oxidative stress and the impairment in antioxidant enzyme activities, inhibited NF-kappaB activation, and prevented expression of iNOS. Dietary glycine blocks activation of different mediators involved in the pathophysiology of liver injury after shock.