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Aim To investigate the effects of starfish saponins(Sfs) on insulin signaling pathway in orotic acid-induced NAFLD rats.Methods 1% orotic acid was used to establish NAFLD model in male Wistar rats for six weeks.The NAFLD rats were randomly divided into two groups(eight rats in each group) and then fed with the corresponding diets: Model group(1% orotic acid)and Sfs group(1% orotic acid containing 0.04% starfish saponins).After starfish saponins feeding for 8 weeks, hepatic lipids content, liver function indices and relevant protein expression in muscle insulin signaling pathway were measured.Results Compared with model group, starfish saponins reduced hepatic lipids content and improved liver functions.In addition, it effectively ameliorated insulin resistance by improving insulin signaling pathway and improved glucose uptake in muscle.Conclusion The amelioration effect of starfish saponins on impaired insulin signaling pathway in muscle is observed in orotic acid-induced NAFLD rats.
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Lysinuric protein intolerance (LPI) is an inborn error of dibasic amino acid transport due to a defect in the dibasic amino acid transporter in the renal and intestine and has a heterogenous presentation. Three Malaysian patients with LPI were studied and their biochemical and molecular findings compared. There were differences and similarities in the biochemical and molecular findings. Molecular analysis of SLC7A7 gene revealed a novel mutation c.235G>A; p.(Gly79Arg) in exon three in Patient 1 and a mutation c.1417C>T; p.(Arg473*) in exon 10 in patient 2 and 3. The degree of concentration of dibasic amino acids may determine the type of disease of the cell membrane transport, however, a positive molecular confirmation will secure the diagnosis.
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The present study was conducted to elucidate the metabolic pathways by which enlarged liver size of patients undergoing disorders of orotic acid de novo metabolism and those patients of enlarged liver size induced by di(2-ethyl hexyl) phthalate in rats as animal model. The results showed that rats-treated with orotic acid generated liver triglyceride content 400% higher than that of the control accompanied with a significant decrease of phospholipid levels (P<0.05). The rates of lipogenic enzymes, both fatty acid synthase (FAS) and phosphatidate phosphohydrolase (PAP), increase accompanying promotions of liver triglyceride content without any changes in fatty acid degradation pathway. However, those rats-treated with di(2- ethyl hexyl) phthalate generated liver phospholipid level significantly higher than of the control accompanied with a markedly decreased the liver triglyceride levels. Both FAS and PAP activities were almost similar with those controls but the rates of fatty acid degradation were increased approximately by 2.5-fold of control. In conclusion: The enlargement of liver size induced by orotic acid is associated with largely retains triglyceride molecules in liver tissues, whereas those induced by di(2-ethyl hexyl) is associated with the induction of phosphorylation generating an increase of liver phospholipid levels.
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Las vitaminoterapias han sido ampliamente utilizadas en neurología para el tratamiento de neuritis o la correción de déficit metabólicos. En Cuba, se produce desde hace algunos años el preparado vitamínico Compvit®, que contiene vitaminas B1, B6 y B12. El ácido orótico, también llamado vitamina B13, es un producto natural que ha mostrado acciones como nootrópico en estudios con animales jóvenes y viejos que acusan deterioro cognitivo. En el presente trabajo se reportan los resultados de un estudio realizado para evaluar las potencialidades terapéuticas del Compvit® y del ácido orótico, empleando la lesión del sistema fimbria-fornix, que afecta severamente las capacidades de aprendizaje de los animales. Los resultados confirman un efecto positivo de cada uno de los tratamientos vitamónicos mejorando las capacidades cognitivas afectadas por la lesión. Aunque ninguno de los productos empleados o su combinación fue capaz de elevar el rendimiento cognitivo al nivel de los animales sanos, todos logran mejorías signficativas en comparación con el placebo. Este trabajo constituye una evidencia adicional en favor del uso terapéutico de compuestos vitamínicos como parte del tratamiento neurorrestaurativo
Vitamin therapies have been widely used in Neurology for the treatment of neuritis or the correction of metabolic deficits. In Cuba, Compvit® (B1, B6 and B12 vitamins) have been produced since several years. Orotic acid, also called vitamin B13 is a natural product showing nootropic actions in studies with young and old cognitively impaired animals. The present paper reports the results of a study conducted to assess the therapeutic potentials of Compvit® and orotic acid, in the recovery of cognitive abilities in fimbria-fornix lesioned animals, a lesion known to severely impair learning abilities. The results confirm positive effects of each vitamin treatment to improve the cognitive abilities affected by lesion. Although none of the products used, neither their combination, was able to raise the cognitive performance to the level of non-lesioned animals, both of them achieve significant improvement compared to placebo. The present paper constitutes additional evidence favoring the therapeutic use of vitamin compounds as part of neurorestorative treatments
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Se presenta un método simple de lesión del nervio periférico por pinzamiento del nervio ciático, y de evaluación conductual de la lesión y su recuperación empleando la marcha sobre una rejilla metálica. La lesión del ciático dificulta el desplazamiento de los animales sobre este sustrato como lo demuestran el aumento significativo de la latencia de escape hacia la caja de habitación y el incremento de fallos en el apoyo de la pata lesionada. Empleando este método se evaluó el efecto de la administración poslesional del complejo vitamónico Compvit B® y del ácido orótico (un precursor de nucleótidos de pirimidina) sobre la recuperación del nervio dañado. Ambos tratamientos y su combinación, mejoraron significativamente la recuperación del nervio lesionado al ser comparados con controles tratados con solución salina
The paper describes a simple method to injure the peripheral sciatic nerve by clamping, along with a behavioral test to asses the lesion and its recovery using the gait on a metallic grid. Sciatic nerve lesion impairs the displacement of the animals on this surface as demonstrated by the significant increase in the escape latency towards the room cage and the increased number of stance failures with the injured leg. Using this method we assessed the effect of post-injury administration of Compvit B® (vitamin compound) and orotic acid (a pyrimidine-nucleotide precursor) on the recovery of injured nerve. Both treatments and its combination, improved significantly the recovery of injured nerve compared to controls treated with saline solution
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Aim: Objectives To evalate the differences in metabolic responses between dietary orotic acid and adenine in lipid profi les of serum and liver tissues. Methods: Rats were paired-fed 1.0 % orotic acid (orotic acid group) and 0.25 % adenine (adenine group) diets or a non-supplemented diet (control group) for 10 days. Serum lipid concentrations were measured using enzyme assay kits. Lipids of liver tissues were extracted and the lipid contents were determined. Results: Serum lipid concentrations (in mg/dL) of adenine group tended to increase whereas those levels decreased in orotic acid group compared to control group. The serum triglyceride (TG) concentrations of control, orotic acid, and adenine groups were (78.1±14.9), (69.0±23.6), and (136.1±21.6); phospholipids (PL): (109.2±11.5), (93.3±10.5), and (131.3±11.0); total cholesterol: (53.7±4.6), (42.9±6.5), and (68.1±5.8); and high-density lipoprotein (HDL)-cholesterol: (35.4±2.7), (33.0±3.0), and (44.7±2.7), respectively. Furthermore, liver TG content of orotic acid group markedly increased. The increase was approximately by 10-fold in comparison to other groups (P<0.05). The lipid contents of liver tissues (in mg/g tissue) in ordinarily of those three groups for TG were (11.4±1.3), (123.5±15.2), and (11.9±1.2); PL: (27.1±0.8), (25.4±1.3), and (30.7±0.6); and the total cholesterol: (2.73±0.09), (2.34±0.12), and (2.91±0.08), respectively. The liver PL and cholesterol content of adenine group increased by 21% and 25% than that of orotic acid group, but both lipid levels of the latter group increased by 7% and 15%, respectively, than that of the control group. Conclusion: Dietary adenine enhances the serum TG, PL, cholesterol, and HDL-cholesterol and the liver PL and cholesterol but without alters the liver TG levels. Dietary orotic acid, however, attenuates these serum lipid levels but retains those lipids synthesized in liver cells, mainly TG.
Subject(s)
Liver , Orotic Acid , AdenineABSTRACT
Objective To investigate the mechanism of orotic acid-induced fatty liver in rats. Method Rats were randomly divided into 2 groups,and fed AIN93 diet with or without 1% orotic acid (OA) for 10d. Serum total cholesterol (TC),triglyceride (TG),high density lipoprotein-cholesterol (HDL-C),hepatic lipids concentrations (TG,TC and phospholipids),hepatic enzymes activities and mRNA levels of key enzymes related to lipids metabolism,as well as hepatic genes expression of transcription factors were determined. Results OA administration significantly increased serum and hepatic TG concentration. The activity and mRNA level of fatty acid synthase (FAS) were obviously up-regulated by OA treatment,whereas the activities and mRNA concentrations of carnitin palmitoyl transferase (CPT) and microsomal triglyceride transfer protein (MTP) were depressed significantly. Furthermore,OA also stimulated the mRNA expression of sterol regulatory element binding protein-1c (SREBP-1c),but did not alter the mRNA concentrations of peroxisome proliferator-activated receptor alpha (PPAR?) in liver. Conclusion:The stimulation of TG synthesis caused by enhancement of SREBP-1c and its target genes-FAS,which could be responsible for development of fatty liver. On the other hand,the inhibition of fatty acid beta-oxidation and VLDL secretion were related to the observed lipids accumulation.