scholarly journals The effect of casein glycomacropeptide versus free synthetic amino acids for early treatment of phenylketonuria in a mice model

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0261150
Author(s):  
Kirsten K. Ahring ◽  
Frederik Dagnæs-Hansen ◽  
Annemarie Brüel ◽  
Mette Christensen ◽  
Erik Jensen ◽  
...  

Introduction Management of phenylketonuria (PKU) is mainly achieved through dietary control with limited intake of phenylalanine (Phe) from food, supplemented with low protein (LP) food and a mixture of free synthetic (FS) amino acids (AA) (FSAA). Casein glycomacropeptide (CGMP) is a natural peptide released in whey during cheese making by the action of the enzyme chymosin. Because CGMP in its pure form does not contain Phe, it is nutritionally suitable as a supplement in the diet for PKU when enriched with specific AAs. Lacprodan® CGMP-20 (= CGMP) used in this study contained only trace amounts of Phe due to minor presence of other proteins/peptides. Objective The aims were to address the following questions in a classical PKU mouse model: Study 1, off diet: Can pure CGMP or CGMP supplemented with Large Neutral Amino Acids (LNAA) as a supplement to normal diet significantly lower the content of Phe in the brain compared to a control group on normal diet, and does supplementation of selected LNAA results in significant lower brain Phe level?. Study 2, on diet: Does a combination of CGMP, essential (non-Phe) EAAs and LP diet, provide similar plasma and brain Phe levels, growth and behavioral skills as a formula which alone consist of FSAA, with a similar composition?. Material and methods 45 female mice homozygous for the Pahenu2 mutation were treated for 12 weeks in five different groups; G1(N-CGMP), fed on Normal (N) casein diet (75%) in combination with CGMP (25%); G2 (N-CGMP-LNAA), fed on Normal (N) casein diet (75%) in combination with CGMP (19,7%) and selected LNAA (5,3% Leu, Tyr and Trp); G3 (N), fed on normal casein diet (100%); G4 (CGMP-EAA-LP), fed on CGMP (70,4%) in combination with essential AA (19,6%) and LP diet; G5 (FSAA-LP), fed on FSAA (100%) and LP diet. The following parameters were measured during the treatment period: Plasma AA profiles including Phe and Tyr, growth, food and water intake and number of teeth cut. At the end of the treatment period, a body scan (fat and lean body mass) and a behavioral test (Barnes Maze) were performed. Finally, the brains were examined for content of Phe, Tyr, Trp, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT) and 5-hydroxyindole-acetic acid (5-HIAA), and the bone density and bone mineral content were determined by dual-energy x-ray absorptiometry. Results Study 1: Mice off diet supplemented with CGMP (G1 (N-CGMP)) or supplemented with CGMP in combination with LNAA (G2 (N-CGMP-LNAA)) had significantly lower Phe in plasma and in the brain compared to mice fed only casein (G3 (N)). Extra LNAA (Tyr, Trp and Leu) to CGMP did not have any significant impact on Phe levels in the plasma and brain, but an increase in serotonin was measured in the brain of G2 mice compared to G1. Study 2: PKU mice fed with mixture of CGMP and EAA as supplement to LP diet (G4 (CGMP-EAA-LP)) demonstrated lower plasma-Phe levels but similar brain- Phe levels and growth as mice fed on an almost identical combination of FSAA (G5 (FSAA-LP)). Conclusion CGMP can be a relevant supplement for the treatment of PKU.

Author(s):  
Zahra Heidari ◽  
Shabnam Mohammadi ◽  
Mahdieh Yousefi Taba

Background: Curcumin is the most active ingredient in turmeric root of Curcuma longa of the Zingiberaceae family and has a potent antioxidant activity. This study aimed at investigating the effects of curcumin with various doses on the density of dark neurons in the hippocampus of induced D-galactose aging mice model. This experimental study was conducted on 40 adult male BALB/c mice. Materials and Methods: We randomly divided animals into 5 groups: D-galactose, control, and curcumin 1, curcumin 2, and curcumin 3 groups. D-galactose (300 mg/kg) was intraperitoneally injected into the D-galactose group for 6 weeks. D-galactose and doses of 25, 50, and 100 mg of curcumin were administrated, respectively, to the curcumin groups 1-3 every day for 14 days. After 6 weeks, the mice’s brains were stained with toluidine blue after tissue passage. Then, the mean dark neuron volume density in each unit of the tissue was assessed using stereological formulas. The obtained data were analyzed by Aanlysis of Variance (ANOVA) in SPSS. Results: Compared with the control group, the average number of dark neurons in the hippocampus significantly increased following the administration of D-galactose (P=0.001). The average dark neurons frequency in the hippocampus significantly decreased in the 50 and 100 mg/kg curcumintreated groups (P=0.001 for both) compared to that of the D-galactose treated animals. Conclusion: The results of this study showed that treatment with 100 mg/kg of curcumin reduced the number of dark neurons in the hippocampus of the aging mice. It seems that curcumin decreases dark neurons via the reduction of apoptosis. Also, curcumin is a powerful antioxidant and affects the level of antioxidant status in the brain.


2018 ◽  
Vol 46 (1) ◽  
pp. 8
Author(s):  
Mehmet Önder Karayiğit ◽  
Murat Yarım

Background: Demyelination refers to the degradation or loss of myelin sheath. In demyelination model studies, it has been reported that demyelination is regressed by giving steroid hormones such as estrogen and progesterone. However, there are not many studies investigating the synthesis of these two hormones by the brain during demyelination and remyelination. Neurosteroids are steroid hormones synthesized by the brain independently from peripheral tissues. In this study, it was aimed to have knowledge about the synthesis of these two hormones by the brain in experimentally formed demyelination process in brains of C57BL/6 mice and their role in the cellular response formed in the region.Materials, Methods & Results: In the study, 36 C57BL/6 mice were used: 12 mice were fed normal diet for 12 weeks as control group (Group I); 12 of them were fed 0.2% cuprizone diet for 12 weeks (Group II) and 12 mice were fed normal diet for 4 weeks after feeding cuprizone diet for 8 weeks (Group III). At the end of the experiment, mice were perfused with 4% paraformaldehyde and brain tissues were blocked in paraffin. 6 μm-thick section was taken from each block. Sections were stained histologically with LFB staining and immunohistochemically with MBP staining in order to determine the demyelination in sections. All sections were also immunohistochemically stained with GFAP to detect astrocytes, with NG2 to detect young OPCs, with aromatase for estrogen synthesis and with 3βHSD antibodies for progesterone synthesis. At the end of the study, complete myelination was observed in group I, while severe demyelination was determined in group II as a result of blind evaluation of LFB and MBP staining by two pathologists. In group III, demyelination was found to be mild. In immunostaining with GFAP and NG2 antibodies, the number of GFAP and NG2 positive cells in Group II was found to be increased compared to the control group. The difference between these two groups was statistically significant (P < 0.01). In group III, the number of GFAP and NG2 positive cells were found to be increased compared to the control group; however, it was found to be lower than that in experimental group II (P < 0.01). In immunohistochemical staining with aromatase and 3βHSD antibody, there was no staining observed in the control groups. While an intense staining was observed in experimental group II, fewer glial staining was noticed in experimental group III when compared to the experimental group II. The difference between these two groups was found to be statistically significant (P ˂ 0.01).Discussion: Aromatase is an enzyme that converts testosterone into estrogen. On the other hand, 3βHSD is an enzyme that converts pregnenolone to progesterone. Expression of aromatase from tissues refers to the synthesis of estrogen and expression of 3βHSD refers to progesterone synthesis. In previous demyelination studies carried out with cuprizone, it has been reported that demyelination is regressed by giving estrogen and progesterone during demyelination. In the presented study, we observed that enzyme levels that catalyze the synthesis of estrogen and progesterone increased during demyelination. In the study, it was determined that estrogen and progesterone levels were increased in the region by enzymes released from the glial cells of the brain as a response to damage formed during demyelination. Interestingly, during the period in which cuprizone was excluded from the diet, it was observed that remyelination began to be formed again and that enzyme levels synthesizing these hormones started to decrease. These results suggested that estrogen and progesterone may be synthesized in the brain after a damage and may contribute to remyelination by initiating a number of cell to cell signaling steps.


Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3225
Author(s):  
Zhaoming Yan ◽  
Yinzhao Zhong ◽  
Yunju Yin ◽  
Yehui Duan ◽  
Wenlong Wang ◽  
...  

This study was conducted to evaluate the effects of tea powder in diets on the growth performance, meat quality, muscular amino acid, fatty acid profile, and serum biochemical indices of pigs. A total of 120 local Chinese pigs (Tibetan × Bama miniature pigs) were randomly assigned to five treatment groups, each with six pens and four pigs per pen. During a 60-day experiment, these groups of pigs were fed the normal diet and the diet supplemented with 1%, 2%, 4%, and 6% tea powder, respectively. The results showed that the supplementation of tea powder did not affect the growth performance of pigs. However, the dietary tea powder inclusion decreased (p < 0.05) the average fat thickness, total fat, and abdominal fat, and increased (p < 0.05) the total muscle as well. In addition, the dietary 2% tea powder decreased (p < 0.05) the muscle lightness (L*) and yellowness (b*). Compared with the control group, the dietary supplementation with 1%, 2%, and 4% tea powder raised (p < 0.05) the total amino acids (TAA) and essential amino acids (EAA), and dietary 4% and 6% tea powder increased (p < 0.05) the C20:5n3 in the muscle tissue. Furthermore, the serum lipid metabolism-related biochemical indices and mRNA expression levels were improved with the addition of tea powder. These results indicated that dietary tea powder might improve the carcass traits and meat quality of the Chinese native finishing pigs, but it does not affect their growth performance. Tea powder could be fully developed and reasonably applied as a dietary supplement.


2021 ◽  
Author(s):  
Hetong Li ◽  
Yu Gou ◽  
Yunpeng Hu ◽  
Qiangqiang Lian ◽  
Faming Tian ◽  
...  

Abstract ObjectivesThis study aimed to evaluate the effects of simvastatin on the metabolism of cartilage and subchondral bone in a mice model of osteoarthritis (OA) induced by obesity. MethodsWe randomly assigned thirty C57BL/6J mice into 3 groups: the Control group received normal diet, the HFD group and HFD+S group received high-fat diet, HFD+S group were simultaneously treated with simvastatin (10 mg/kg/day) for 8 weeks. The pathology of OA was assessed by histomorphology analyses, immunohistochemistry, micro-computed tomography and enzyme-linked immunosorbent assay. ResultsHistomorphological analysis revealed that OA was significantly exacerbated by the HFD-induced obesity and markedly alleviated by the simvastatin intervention. In details, simvastatin ameliorated the abnormal metabolic status and cartilage lesions, significantly increased aggrecan and collagen-II expression and decreased the expression of MMP-13. Furthermore, the results of micro-computed tomography analysis revealed that the HFD+S group exhibited higher BMD, BV/TV, and Tb.N values but a lower Tb.Sp value than that of the HFD group. Serum COMP concentrations, the number of adipocytes in subchondral bone marrow and the number of osteoclasts on trabecular bone surface were significantly correlated with OARSI score. ConclusionsIn conclusion, HFD-induced obesity aggravates articular degeneration and abnormal metabolic pathology in subchondral bone, which could be reversed by the intervention of simvastatin, suggesting that simvastatin may be a potential candidate for amelioration of the progression of OA.


2021 ◽  
Vol 9 (A) ◽  
pp. 343-351
Author(s):  
Satuman Satuman ◽  
Desi Sandra Sari ◽  
Eva Rachmi ◽  
Eddy Herman Tanggo ◽  
Hari Basuki Notobroto ◽  
...  

AIM. The aim of the study was to analyze Avra's effector in inducing cancer stem cells into colon cancer through increased radical oxygen species (ROS), PTEN expression and c-myC as markers of tumorigenesis in mice model of the colorectal cancer infected with S. typhimurium. METHODS. The study used balb c mice induced once a week by 10 mg / mL / day of AOM for 1-week and 12-week treatment period. Isolation of S. typhimurium specific protein had been carried out before being induced to mice in intraperitoneal manner in the amount of 40 mL / 50 mL. Propagation of S. typhimurium ATCC bacteria with MacConkey media and isolation of S. typhimurium protein were administered. The sample was divided into 4 groups, positive control group (group that was only exposed to azoxymethane (AOM), group exposed to both AOM and AvrA (AOM + AvrA), and group exposed to both AOM and S. typhimurium (AOM + S. typhimurium). Blood flow cytometry and soft tissue sampling for IHC and data analysis were then conducted. RESULTS. The results of the study showed that there was an increase in the expression of ROS, PTEN and c-Myc. Increased ROS expression was found in the 12-week treatment period group and it was known that such increase was due to AOM + S. typhimurium (45.78 ± 2.93) induction compared to AOM, AOM + AvrA and control (p <0.05). PTEN and C-myc expression increased at the 12th week compared to the negative control. CONCLUSION. Inflammation is the triggering factor for colorectal cancer, in which the expression of ROS, PTEN and c-Myc as the colorectal cancer markers increases in both the acute and chronic phases.


Author(s):  
Zafer Sahin ◽  
Alpaslan Ozkurkculer ◽  
Omer Faruk Kalkan ◽  
Ahmet Ozkaya ◽  
Aynur Koc ◽  
...  

Abstract. Alterations of essential elements in the brain are associated with the pathophysiology of many neuropsychiatric disorders. It is known that chronic/overwhelming stress may cause some anxiety and/or depression. We aimed to investigate the effects of two different chronic immobilization stress protocols on anxiety-related behaviors and brain minerals. Adult male Wistar rats were divided into 3 groups as follows ( n = 10/group): control, immobilization stress-1 (45 minutes daily for 7-day) and immobilization stress-2 (45 minutes twice a day for 7-day). Stress-related behaviors were evaluated by open field test and forced swimming test. In the immobilization stress-1 and immobilization stress-2 groups, percentage of time spent in the central area (6.38 ± 0.41% and 6.28 ± 1.03% respectively, p < 0.05) and rearing frequency (2.75 ± 0.41 and 3.85 ± 0.46, p < 0.01 and p < 0.05, respectively) were lower, latency to center area (49.11 ± 5.87 s and 44.92 ± 8.04 s, p < 0.01 and p < 0.01, respectively), were higher than the control group (8.65 ± 0.49%, 5.37 ± 0.44 and 15.3 ± 3.32 s, respectively). In the immobilization stress-1 group, zinc (12.65 ± 0.1 ppm, p < 0.001), magnesium (170.4 ± 1.7 ppm, p < 0.005) and phosphate (2.76 ± 0.1 ppm, p < 0.05) levels were lower than the control group (13.87 ± 0.16 ppm, 179.31 ± 1.87 ppm and 3.11 ± 0.06 ppm, respectively). In the immobilization stress-2 group, magnesium (171.56 ± 1.87 ppm, p < 0.05), phosphate (2.44 ± 0.07 ppm, p < 0.001) levels were lower, and manganese (373.68 ± 5.76 ppb, p < 0.001) and copper (2.79 ± 0.15 ppm, p < 0.05) levels were higher than the control group (179.31 ± 1.87 ppm, 3.11 ± 0.06 ppm, 327.25 ± 8.35 ppb and 2.45 ± 0.05 ppm, respectively). Our results indicated that 7-day chronic immobilization stress increased anxiety-related behaviors in both stress groups. Zinc, magnesium, phosphate, copper and manganese levels were affected in the brain.


Author(s):  
YanuarEka P. ◽  
Hendy Hendarto ◽  
Widjiati .

Retrograde menstruation lead to I Kappa B Kinase (IKK) fosforilation in peritoneum macrophage and cause secretion of proinflammatory cytokine interleukin1β then stimulate endometriosis cell to produce Vascular Endothelial Growth Factor which lead to increasing of endometriosis lession seen as endometriosis implant area. Cytokine secretion was inhibited through prevention of NF-κB activation by dragon red fruit rind extract (Hylocereuspolyrhizus). The aim of this reserach is to know the effect of dragon red fuit rind extract with 0,25; 0,5; and 1 mg/g bodyweight dosage toward IL-1β, VEGF expression and implant area in endometriosis mice model. The design of this experiment was randomized post test only control group design.Endometrios mice model were made in 14 days and split into two group, positive control group and treatment group after two week negative control group and postive control group were given Na-CMC 0,5% solution consequetively, and treatment group were given dragon red fruit extract with different dosage. Signification number for IL-1β is p>0,05, signification number for VEGF is p>0,05, and implant area signification number is p>0,05. Administration of dragon red fruit rind extract can decrease IL-1β, VEGF, and implant area.


2020 ◽  
Vol 23 (5) ◽  
pp. 402-410 ◽  
Author(s):  
Lin-Zi Li ◽  
Shan-Shan Lei ◽  
Bo Li ◽  
Fu-Chen Zhou ◽  
Ye-Hui Chen ◽  
...  

Aim and Objective: The Dendrobium officinalis flower (DOF) is popular in China due to common belief in its anti-aging properties and positive effects on “nourish yin”. However, there have been relatively few confirmatory pharmacological experiments conducted to date. The aim of this work was to evaluate whether DOF has beneficial effects on learning and memory in senescent rats, and, if so, to determine its potential mechanism of effect. Materials and Methods: SD rats were administrated orally DOF at a dose of 1.38, or 0.46 g/kg once a day for 8 weeks. Two other groups included a healthy untreated control group and a senescent control group. During the 7th week, a Morris water maze test was performed to assess learning and memory. At the end of the experiment, serum and brain samples were collected to measure concentrations of antioxidant enzymes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH-Px) in serum, and the neurotransmitters, including γ-aminobutyric acid (γ-GABA), Glutamic (Glu), and monoamine oxidase B (MAO-B) in the brain. Histopathology of the hippocampus was assessed using hematoxylin-eosin (H&E) staining. Results: The results suggested that treatment with DOF improved learning as measured by escape latency, total distance, and target quadrant time, and also increased levels of γ-GABA in the brain. In addition, DOF decreased the levels of MDA, Glu, and MAO-B, and improved SOD and GSHPx. Histopathological analysis showed that DOF also significantly reduced structural lesions and neurodegeneration in the hippocampus relative to untreated senescent rats. Conclusion: DOF alleviated brain aging and improved the spatial learning abilities in senescent rats, potentially by attenuating oxidative stress and thus reducing hippocampal damage and balancing the release of neurotransmitters.


2020 ◽  
Vol 22 (9) ◽  
pp. 657-662 ◽  
Author(s):  
Mustafa Celik ◽  
Alper Şen ◽  
İsmail Koyuncu ◽  
Ataman Gönel

Aim and Objective:: To determine the mechanisms present in the etiopathogenesis of nasal polyposis. It is not clear whether amino acids contribute in a causal way to the development of the disease. Therefore, the aim of this study was to determine the plasma-free amino acid profile in patients with nasal polyposis and to compare the results with a healthy control group. Materials and Methods:: This was a prospective controlled study that took place in the Otolaryngology Department at the Harran University Faculty of Medicine between April 2017 and April 2018. Plasmafree amino acid profile levels were studied in serum samples taken from a patient group and a healthy control group. Patients who were diagnosed with bilateral diffuse nasal polyposis and were scheduled for surgical interventions were included in this study. Individuals whose age, gender, and body mass index values were compatible with that of the patient group and who did not have any health problems were included in the control group. All the participants whose levels of plasma-free amino acid were thought to be affected by one or more of the following factors were excluded from the study: smoking and alcohol use, allergic rhinitis presence, the presence of acute or chronic sinusitis, a history of endoscopic sinus surgery, unilateral nasal masses, a history of chronic drug use, systemic or topical steroid use in the last three months for any reason, and liver, kidney, hematological, cardiovascular, metabolic, neurological, or psychiatric disorders or malignancies. Results: In patients with nasal polyposis, 3-methyl histidine (3-MHIS: nasal polyposis group (ng) = 3.22 (1.92 – 6.07); control group (cg) = 1.21 (0.77 – 1.68); p = 0.001); arginine (arg: ng = 98.95 (70.81 – 117.75); cg = 75.10 (54.49 – 79.88); p = 0.005); asparagine (asn: ng = 79.84 (57.50 – 101.44); cg = 60.66 (46.39 – 74.62); p = 0.021); citrulline (cit: ng = 51.83 (43.81 – 59.78); cg = 38.33 (27.81 – 53.73); p = 0.038); cystine (cys: ng = 4.29 (2.43 – 6.66); cg = 2.41 (1.51 – 4.16); p = 0.019); glutamic acid (glu: ng = 234.86 (128.75 – 286.66); cg = 152.37 (122.51 – 188.34); p = 0.045); histidine (his: ng = 94.19 (79.34 – 113.99); cg = 74.80 (62.76 – 98.91); p = 0.018); lysine (lys: ng = 297.22 (206.55 – 371.25); cg = 179.50 (151.58 – 238.02); p = 0.001); ornithine (ng = 160.62 (128.36 – 189.32); cg = 115.91 (97.03 – 159.91); p = 0.019); serine (ser: ng = 195.15 (151.58 – 253.07); cg = 83.07 (67.44 – 92.44); p = 0.001); taurine (tau: ng = 74.69 (47.00 – 112.13); cg = 53.14 (33.57 – 67.31); p = 0.006); tryptophan (trp: ng = 52.31 (33.81 – 80.11); cg = 34.44 (25.94 – 43.07); p = 0.005), homocitrulline (ng = 1.75 (1.27 – 2.59); cg = 0.00 (0.00 – 0.53); p = 0.001); norvaline (ng = 6.90 (5.61 – 9.18); cg = 4.93 (3.74 – 7.13); p = 0.021); argininosuccinic acid (ng = 14.33 (10.06 – 25.65); cg = 12.22 (5.77 – 16.87) p = 0.046); and plasma concentrations were significantly higher than in the healthy control group (p <0.05). However, the gamma-aminobutyric acid (gaba: ng = 0.16 (0.10 – 0.24); cg = 0.21 (0.19 – 0.29); p = 0.010) plasma concentration was significantly lower in the nasal polyposis group than in the healthy control group. Conclusion: In this study, plasma levels of 15 free amino acids were significantly higher in the nasal polyposis group than in the healthy control group. A plasma level of 1 free amino acid was found to be significantly lower in the nasal polyposis group compared to the healthy control group. Therefore, it is important to determine the possibility of using the information obtained to prevent the recurrence of the condition and to develop effective treatment strategies. This study may be a milestone for studies of this subject. However, this study needs to be confirmed by further studies conducted in a larger series.


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