Nutrient Intake and Gut Microbial Genera Changes after a 4-Week Placebo Controlled Galacto-Oligosaccharides Intervention in Young Females.

Recent interest in the gut-brain-axis has highlighted the potential of prebiotics to impact wellbeing, and to affect behavioral change in humans. In this clinical trial, we examined the impact of four-weeks daily supplementation of galacto-oligosaccharides (GOS) on self-reported nutrient intake and relationships on gut microbiota in a four-week two-armed parallel double-blind placebo controlled GOS supplement trial in young adult females. Food diaries and stool samples were collected prior to and following 28 days of supplement consumption. It was found that four weeks of GOS supplementation influenced macronutrient intake, as evident by reduced carbohydrate and sugars and increased fats intake. Further analysis showed that the reduction in carbohydrates was predicted by increasing abundances of Bifidobacterium in the GOS group in comparison to the placebo group. This suggests that Bifidobacterium increase via GOS supplementation may help improve the gut microbiota composition by altering the desire for specific types of carbohydrates and boosting Bifidobacterium availability when fiber intake is below recommended levels, without compromising appetite for fiber from food.

Maternal galactooligosaccharides supplementation programmed immune defense, microbial colonization and intestinal development in piglets.

The benefits of galactooligosaccharides (GOS) in neonates have been confirmed. However, the effects of nutritional programming by maternal GOS intervention on microbial colonization and intestinal development in the offspring remain unclear. In the present study, late gestational sows were fed with GOS (10 g d-1 added into the diet) or not until parturition, and the performances, immune status, microbiota composition and intestinal barriers in their piglets on day 21 were compared. GOS supplementation in pregnant sows improved their litter characteristics and the growth performance of their piglets during the neonatal stage (day 21), and elevated the plasma IgA levels in both sows and their piglets (P < 0.05). GOS intervention enriched fecal Alloprevotella and Ruminoclostridium_1 in gestational sows and vertically increased fecal Alloprevotella and Ruminococcaceae in their piglets (P < 0.05). Moreover, maternal GOS intervention increased fecal acetate (P < 0.05) and improved the intestinal barriers of their piglets by upregulating intestinal tight junctions (Occludin, Claudin-1, ZO-1), the goblet cell number and Mucin-2 (P < 0.05), which correlated positively with the colonized microbiota (P < 0.05). In summary, GOS supplementation for sows during late gestation nutritionally programmed maternal specific microbes and IgA of their offspring. This neonatal programming showed positive potential in promoting the intestinal barriers, immune defense, and growth performance of the piglets. Our findings provide evidence for maternal nutritional programming in neonates and insights for future application of GOS in maternal-neonatal nutrition.

Hyperbaric oxygen therapy effectively alleviates D-galactose-induced-age-related cardiac dysfunction via attenuating mitochondrial dysfunction in pre-diabetic rats.

Currently, the prevalence of obesity in aging populations is fast growing worldwide. Aging induced by D-galactose (D-gal) is proven to cause the worsening of cardiac dysfunction in pre-diabetic rats via deteriorating cardiac mitochondrial function. Hyperbaric oxygen therapy (HBOT) has been shown to attenuate D-gal-induced cognitive deterioration through decreased inflammation and apoptosis. We tested the hypothesis that HBOT alleviates D-gal induced cardiac dysfunction via improving mitochondrial function in pre-diabetic rats. Wistar rats (n=56) were fed normal diet or high-fat diet for 12 weeks. For subsequent 8 weeks, they were subcutaneously injected either vehicle (0.9% normal saline) or D-gal (150mg/kg/day). Rats were randomly subdivided into 7 groups at week 21: sham-treated (normal diet fed rats with vehicle (NDV), high-fat diet fed rats with vehicle (HFV), normal diet fed rats with D-gal (NDDg), high-fat diet fed rats with D-gal (HFDg)) and HBOT-treated (HFV, NDDg, HFDg). Sham rats received ambient pressure of oxygen while HBOT-treated ones received 100% oxygen given once daily for 60 minutes at 2 atmosphere absolute. HBOT reduced metabolic impairments, mitochondrial dysfunction and increased autophagy, resulting in an improvement of cardiac function in aged pre-diabetic rats.

Ginsenoside Rg1 ameliorates the cognitive deficits in D-galactose and AlCl3-induced aging mice by restoring FGF2-Akt and BDNF-TrkB signaling axis to inhibit apoptosis.

Ginsenoside Rg1 is the main active ingredient of Panax ginseng with the activity of neuroprotective, antioxidant and strengthening the immune system. Therefore, we hypothesized that Rg1 may afford anti-aging effects although the mechanism remains to be elucidated. In this study, chemically induced aging mice were established by consecutive administration of D-galactose and AlCl3. We found that Rg1 effectively ameliorates spatial learning and memory deficits in aging mice demonstrated by their improved performance in step down avoidance tests and Morris water maze experiments. Rg1 restored aging-induced decline of FGF2 and BDNF, reactivated TrkB/Akt signaling pathways in the hippocampus and prefrontal cortex to inhibit apoptosis, for the expression of anti-apoptotic protein Bcl-2 and apoptosis promoting enzyme cleaved-Caspase3 were antagonistically restored. Therefore, these results established the anti-aging effects of Rg1, and FGF2, BDNF and associated signaling pathways might be promising targets. Our data may provide a new avenue to the pharmacological research and diet therapeutic role of ethnic products such as Rg1 in anti-aging and aging associated diseases.

Anti-Ulcerative Effect of Curcumin-Galactomannoside Complex on Acetic Acid-Induced Experimental Model by Inhibiting Inflammation and Oxidative Stress.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects the mucosa and submucosa of colon. The pathogenesis of ulcerative colitis (UC) is related to reduced antioxidant capacity and increased inflammatory processes. Reactive oxygen metabolites are the potent inflammatory mediators that may be involved in tissue injury in inflammatory bowel disease. Conventional drug therapies for UC come with a myriad of side effects which further raise the need for natural bioactive agents. Curcumin has proven to be beneficial in the prevention and treatment of a number of inflammatory diseases, but due its poor bioavailability, the therapeutic applications are limited. Thus, to enhance its bioavailability, a new formulation - curcumin-galactomannoside (CGM)- was made by complexing curcumin with galactomannans derived from fenugreek. The present study aims to evaluate the effects of CGM on experimental UC model. Adult male Wistar rats were divided into 5 groups: normal control rats (NC); ulcerative colitis control rats (UC); UC + sulfasalazine (SS) treated; UC + curcumin (CM) treated; and UC + CGM supplemented for 21 days. The colonic mucosal injury was assessed by macroscopic and histological examination, along with evaluation of antioxidant status, inflammatory mediators, and gene expressions. Administration of CGM significantly enhanced antioxidant activities and decreased the level of inflammatory mediators and also suppressed the expression of inflammatory markers as compared with other groups. In conclusion, findings from these results reveal that CGM exerts marked curative effects on acute experimental colitis, possibly by regulating the antioxidant status and modulating inflammatory cascade.

Dissecting the Potential of Selenoproteins Extracted from Selenium-Enriched Rice on Physiological, Biochemical and Anti-Ageing Effects In Vivo.

Ageing is an irreversible phenomenon and the processes which can delay it are under consideration for a long time by the scientific community. Selenium is an important candidate for it, but the impact of selenoprotein on nutritional changes and ageing has not been reported well. In this regard, antioxidant activities and free radical scavenging effect of selenoproteins extracted from selenium-rich rice were studied. Mice were administered a subcutaneous abdominal injection of D-galactose to induce the ageing model and fed with different selenoprotein dosage diet. Deviations among biochemical activities (total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and malondialdehyde (MDA)) in liver and serum of the mice were assessed. The degree of liver injury, antioxidant genes and protein relative expression were estimated. The protein content, selenium content, hydroxyl scavenging and DPPH radicals were accessed in selenoprotein components. The selenoprotein constituent had protein and selenium contents in different components as water-soluble proteins > alkali-soluble proteins > salt-soluble proteins > ethanol-soluble proteins. The enzymatic activity (total antioxidant capacity, GSH-Px and SOD) in liver and serum of mice was significantly enhanced in selenoprotein diet groups. D-Galactose-induced liver injury was significantly reduced by selenoprotein diet of 25 µg/(kg day). Real-time qPCR and Western blot disclosed the enhanced relative expression of antioxidant genes (SOD2, GPX1, TrxR2 and Nrf2) and HO-1 protein in the positive control (Vc) and selenoprotein diet groups. In conclusion, selenoprotein treatment was found to have a positive influence on liver hepatocytes and biochemical features in mice. It might be used as a potential diet in scavenging oxidative injury and supporting enzymatic antioxidant system.

Structural Characterization and Antioxidant Activity of Polysaccharides from Athyrium multidentatum (Doll.) Ching in d-Galactose-Induced Aging Mice via PI3K/AKT Pathway.

The purpose of this study was to characterize the polysaccharides from Athyrium multidentatum (Doll.) Ching (AMC) rhizome and explore the protective mechanism against d-galactose-induced oxidative stress in aging mice. METHODS: A series of experiments, including molecular weight, monosaccharide composition, Fourier transform infrared (FT-IR) spectroscopy, and 1H nuclear magnetic resonance (1H NMR) spectroscopy were carried out to characterize AMC polysaccharides. The mechanism was investigated exploring d-galactose-induced aging mouse model. Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) and western blotting assays were performed to assess the gene and protein expression in liver. KEY FINDINGS: Our results showed that AMC polysaccharides were mainly composed of mannose (Man), rhamnose (Rha), glucuronic acid (Glc A), glucose (Glc), galactose (Gal), arabinose (Ara), and fucose (Fuc) in a molar ratio of 0.077:0.088:0.09:1:0.375:0.354:0.04 with a molecular weight of 33203 Da (Mw). AMC polysaccharides strikingly reversed d-galactose-induced changes in mice, including upregulated phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor-erythroid 2-related factor 2 (Nrf2), forkhead box O3a (FOXO3a), and hemeoxygenase-1 (HO-1) mRNA expression, raised Bcl-2/Bax ratio, downregulated caspase-3 mRNA expression, enhanced Akt, phosphorylation of Akt (p-Akt), Nrf2 and HO-1 protein expression, decreased caspase-3, and Bax protein expression. CONCLUSION: AMC polysaccharides attenuated d-galactose-induced oxidative stress and cell apoptosis by activating the PI3K/AKT pathway, which might in part contributed to their anti-aging activity.

Modulating the site-specific oral delivery of sorafenib using sugar-grafted nanoparticles for hepatocellular carcinoma treatment.

Globally, one in six deaths is reported due to cancer suggesting the critical need for development of advanced treatment regimens. In this study, solid lipid nanoparticles (SLN) were prepared and appended with polyethylene glycol (PEGylated) galactose and a multikinase inhibitor sorafenib (SRFB) was used as chemotherapeutic drug, for treating hepatocellular carcinoma (HCC). The nanoparticles were evaluated for in-vitro and in-vivo performances to showcase the targeting efficiency and therapeutic benefits of the sorafenib loaded ligand conjugated nanoparticles (GAL-SSLN). When compared with SRFB or Sorafenib loaded SLN, GAL-SSLN showed superior cytotoxicity and apoptosis in HepG2 (human hepatocellular carcinoma cells). In addition, in-vivo pharmacokinetics and real time biodistribution studies in BALB/c mice showed that the surface conjugation of nanoparticles with galactose resulted in better pharmacokinetic performance and targeted delivery of the nanoparticles to liver. Results indicated that GAL-SSLN showed promising attributes in terms of targeting sorafenib to liver and therapeutic efficacy.

Comparative immunostimulatory effect of probiotics and prebiotics in Channa punctatus against Aphanomyces invadans.

In aquaculture and human health care probiotics and prebiotics have been widely used due to their important role in enhancing beneficial gut microbiota, promoting growth, increasing disease resistance, and positively modulating the host immune system. This study reports for the first time a comparative analysis on the effect of the probiotics and prebiotics on growth, digestive enzymes activity, antioxidant activity, and immune response in Channa punctatus against Aphanomyces invadans. Among the diets enriched with Saccharomyces cerevisiae (S. cerevisiae) and Galactooligosaccharide (GOS) in C. punctatus, feeding 2.5 g kg-1 diet did not significantly influence the mean weight gain (MWG) between weeks 2 and 4 in both the infected and control groups; however the increase in MWG became significant from weeks 6-8. Similarly, during this period the protein efficiency ratio (PER), feed conversion ratio (FCR) and protein intake (PI) did not increase significantly. The intestinal protease, lipase, and amylase enzyme activities also did not increase significantly between weeks 2 and 4, whereas the values increased significantly after 6 weeks in both groups when fed with dietary supplementation of S. cerevisiae and GOS. The total S. cerevisiae count significantly increased in the gut of infected and non-infected fish fed with S. cerevisiae and GOS diets while the total bacterial (TB) count decreased between weeks 6 and 8. The total superoxide dismutase (t-SOD) activity and the malonaldehyde (MDA) concentration increased significantly in the non-infected fish fed with S. cerevisiae and GOS supplementation diets between weeks 6 and 8 whereas the catalase (CAT) and glutathione peroxidase (GPx) activities increased significantly only on week 8. The innate immune parameters such as plasma lysozyme, acid phosphatase (ACP), and myeloperoxidase (MPO) activities increased significantly in the infected and non-infected fish fed with S. cerevisiae and GOS containing diets after 6 weeks. Similarly, the plasma nitric oxide (NO) level and total protein (TP) content significantly increased in the non-infected fish fed with S. cerevisiae and GOS containing diets between weeks 6 and 8. In the control and the non-infected fish fed with S. cerevisiae and GOS enriched diets caused no mortality whereas 15% and 10% mortality was observed in the infected fish fed with S. cerevisiae and GOS diets, respectively. This study indicates that the infected and non-infected C. punctatus fed with dietary supplementation of GOS diet at 2.5 g kg-1 had exhibited better growth performance, digestive enzyme activities, gut microbiota composition, and immune response than that of S. cerevisiae diet.

RKIP-Mediated NF-κB Signaling is involved in ELF-MF-mediated improvement in AD rat.

In a previous study, we reported the positive effects of extremely low frequency electromagnetic field (ELF-MF) exposure on Alzheimer's disease (AD) rats; however, the underlying mechanism remains unclear. In addition, we found that Raf-1 kinase inhibitor protein (RKIP) was downregulated by microwave exposure in the rat hippocampus. Our hypothesis was that RKIP-mediated NF-κB pathway signaling is involved in the effect of ELF-MF on the AD rat. In this study, D-galactose intraperitoneal (50 mg/kg/d for 42 d) and Aß25-35 hippocampal (5 µL/unilateral, bilateral, single-dose) injection were implemented to establish an AD rat model. Animals were exposed to 50 Hz and 400 µT ELF-MF for 60 continuous days. The spatial memory ability of the rat was then tested using the Morris water maze. Protein expression and interaction were detected by western blotting and co-immunoprecipitation for RKIP-mediated NF-κB pathway factors. The results showed that ELF-MF exposure partially improved the cognitive disorder, upregulated the levels of RKIP, TAK1, and the RKIP/TAK1 interaction, but downregulated p-IKK levels in AD rats. These results indicated that RKIP-mediated NF-κB pathway signaling plays an important role in the ELF-MF exposure-mediated improvements in the AD rat. Our study suggested that ELF-MF exposure might have a potential therapeutic value for AD. Further in depth studies are required in the future.

Modulation of gut microbiota by dietary supplementation with tuna oil and algae oil alleviates the effects of D-galactose-induced ageing.

Previous studies have shown that dietary supplementation with tuna oil and algae oil can alleviate the effects of ageing on learning and memory in mouse models, but the mechanism of this effect remains unknown. This study aimed to determine whether dietary oil supplementation alters the composition of the gut microbiota during the prevention of age-related effects on cognition. Ageing mice received dietary oil supplementation continuously for 12 weeks. The supplementation was found to improve the animals' learning and cognition, and this effect was most marked in the TO200AO400 group, which received a 1:2 mixture of tuna oil and algae oil at 600 mg kg-1 day-1. Next-generation sequencing of the 16S rRNA gene present in faecal samples showed that the gut microbiota varied in the groups that received different oil treatments; the TO200AO400 treatment most closely restored the composition of the D-galactose-altered gut microbiota to that of the control. Moreover, 83 altered operational taxonomic units (OTUs) responsive to dietary oil supplementation were identified; five of these differed in one or more parameters associated with host ageing. In conclusion, this study confirmed the effect of dietary oil supplementation on the alleviation of age-related decline in cognitive function and showed that oil supplementation results in alterations in the composition of the gut microbiota. Further research will be needed to elucidate the causal relationship between the reversal of age-related cognitive decline and gut microbiota modulation and to explore the potential of gut microbial communities as a diagnostic biomarker and a therapeutic target in ageing.

Supplementation of Diet With Galacto-oligosaccharides Increases Bifidobacteria, but Not Insulin Sensitivity, in Obese Prediabetic Individuals.

BACKGROUND & AIMS: The gut microbiota affects host lipid and glucose metabolism, satiety, and chronic low-grade inflammation to contribute to obesity and type 2 diabetes. Fermentation end products, in particular the short-chain fatty acid (SCFA) acetate, are believed to be involved in these processes. We investigated the long-term effects of supplementation with galacto-oligosaccharides (GOS), an acetogenic fiber, on the composition of the human gut microbiota and human metabolism. METHODS: We performed a double-blinded, placebo-controlled, parallel intervention study of 44 overweight or obese (body mass index, 28-40 kg/m2) prediabetic men and women (ages, 45-70 y) from October 2014 through October 2015 in Maastricht, The Netherlands. The participants were assigned randomly to groups who ingested 15 g GOS or isocaloric placebo (maltodextrin) daily with their regular meals for 12 weeks. Before and after this period, we collected data on peripheral and adipose tissue insulin sensitivity, fecal microbiota composition, plasma and fecal SCFA, energy expenditure and substrate oxidation, body composition, and hormonal and inflammatory responses. The primary outcome was the effect of GOS on peripheral insulin sensitivity, measured by the hyperinsulinemic-euglycemic clamp method. RESULTS: Supplementation of diets with GOS, but not placebo, increased the abundance of Bifidobacterium species in feces by 5-fold (P = .009; q = 0.144). Microbial richness or diversity in fecal samples were not affected. We did not observe any differences in fecal or fasting plasma SCFA concentrations or in systemic concentrations of gut-derived hormones, incretins, lipopolysaccharide-binding protein, or other markers of inflammation. In addition, no significant alterations in peripheral and adipose tissue insulin sensitivity, body composition, and energy and substrate metabolism were found. CONCLUSIONS: Twelve-week supplementation of GOS selectively increased fecal Bifidobacterium species abundance, but this did not produce significant changes in insulin sensitivity or related substrate and energy metabolism in overweight or obese prediabetic men and women. ClincialTrials.gov number, NCT02271776.

Infant formula with galacto-oligosaccharides (OM55N) stimulates the growth of indigenous bifidobacteria in healthy term infants.

The objective of the study was to investigate whether an infant formula supplemented with galacto-oligosaccharides (GOS; OM55N) was able to stimulate the growth of indigenous bifidobacteria and to establish microbiota similar to that of breastfed infants. A randomised, double-blind, placebo-controlled trial was performed using 35 healthy term infants (31-54 days of age; 42±6 days) to determine whether infant formula with 0.3 g/dl GOS (OM55N) stimulated the growth of bifidobacteria in the infants' guts. At the trial onset and 2 weeks after, the infants' faecal samples were examined for microbiota composition (bacterial abundance and α-diversity) and faecal characteristics. Among the 35 infants, 5 were withdrawn and 8 were excluded from the final evaluation before breaking the blinding since the indigenous bifidobacteria were not detected at the trial onset. After 2 weeks, the abundance of Bifidobacteriaceae was significantly increased in the GOS feeding group compared to the control (+11.6±24.1% vs -3.9±13.0%; P=0.043). The Shannon index, which accounts for both abundance and evenness of the present species, was significantly decreased with GOS supplementation (-0.1±0.4 vs +0.4±0.4; P=0.014). Faecal characteristics such as pH and organic acids were similar in both groups, with no statistical differences. No adverse side effects related to the formula consumption were reported. Although the concentration of GOS was relatively low, the infant formula with GOS increased the abundance of bifidobacteria and resulted in a reduced α-diversity of the microbiota.

Antioxidative and Neuroprotective Effects of Curcumin in an Alzheimer's Disease Rat Model Co-Treated with Intracerebroventricular Streptozotocin and Subcutaneous D-Galactose.

Epidemiological data imply links between the increasing incidences of Alzheimer's disease (AD) and type 2 diabetes mellitus. In this study, an AD rat model was established by combining treatments with intracerebroventricular streptozotocin (icv-STZ) and subcutaneous D-galactose, and the effects of curcumin on depressing AD-like symptoms were investigated. In the AD model group, rats were treated with icv-STZ in each hippocampus with 3.0 mg/kg of bodyweight once and then were subcutaneously injected with D-galactose daily (125 mg/kg of bodyweight) for 7 weeks. In the curcumin-protective group, after icv-STZ treatment, rats were treated with D-galactose (the same as in the AD model group) and intraperitoneally injected with curcumin daily (10 mg/kg of bodyweight) for 7 weeks. Vehicle-treated rats were treated as control. Compared with the vehicle control, the amount of protein carbonylation and glutathione in liver, as well as malondialdehyde in serum, were upregulated but glutathione peroxidase activity in blood was downregulated in the AD model group. The shuttle index and locomotor activity of rats in the AD model group were decreased compared with the vehicle control group. Furthermore, AD model rats showed neuronal damage and neuron loss with formation of amyloid-like substances and neurofibrillary tangles, and the levels of both ß-cleavage of AßPP and phosphorylation of tau (Ser396) were significantly increased compared with the vehicle control group. Notably, compared with the AD model group, oxidative stress was decreased and the abilities of active avoidance and locomotor activity were improved, as well as attenuated neurodegeneration, in the curcumin-protective group. These results imply the applications of this animal model for AD research and of curcumin in the treatment of AD.

Tanshinone IIA enhances bystander cell killing of cancer cells expressing Drosophila melanogaster deoxyribonucleoside kinase in nuclei and mitochondria.

Heterologous expression of the Drosophila melanogaster multi-substrate deoxyribonucleoside kinase (Dm-dNK) increases the sensitivity of cancer cells to several cytotoxic nucleoside analogs. Thus, it may be used as a suicide gene in combined gene/chemotherapy treatment of cancer. To further characterize this potential suicide gene, we constructed two retroviral vectors that enabled the expression of Dm-dNK in cancer cells. One vector harbored the wild­type enzyme that localized to the nucleus. The other vector harbored a mitochondrial localized mutant enzyme that was constructed by deleting the nuclear localization signal and fusing it to a mitochondrial import signal of cytochrome c oxidase. A thymidine kinase-deficient osteosarcoma cell line was transduced with the recombinant viruses. The sensitivity and bystander cell killing in the presence of pyrimidine nucleoside analogs (E)-5-(2-bromovinyl)­2'­deoxyuridine and 1-ß-D-arabinofuranosylthymine were investigated. Tanshinone IIA is a constituent of Danshen; a traditional Chinese medicine used in the treatment of cardiovascular diseases. This study also looked at the influence of Tanshinone IIA on the bystander effect and the underlying mechanisms. We showed that sensitivity of the osteosarcoma cell line to the nucleoside analogs and the efficiency of bystander cell killing were independent of the subcellular localization of Dm-dNK. The enhanced effect of tanshinone IIA on the bystander effect was related to the increased expression of Cx43 and Cx26.

Effects of temporary low-dose galactose supplements in children aged 5-12 y with classical galactosemia: a pilot study.

BACKGROUND: Classical galactosemia is caused by severe galactose-1-phosphate uridyltransferase deficiency. Despite life-long galactose-restriction, many patients experience long-term complications. Intoxication by galactose and its metabolites as well as over-restriction of galactose may contribute to the pathophysiology. We provided temporary low-dose galactose supplements to patients. We assessed tolerance and potential beneficial effects with clinical monitoring and measurement of biochemical, endocrine, and IgG N-glycosylation profiles. METHODS: We enrolled 26 patients (8.6 ± 1.9 y). Thirteen were provided with 300 mg of galactose/day followed by 500 mg for 2 wk each (13 patient controls). RESULTS: We observed no clinical changes with the intervention. Temporary mild increase in galactose-1-phosphate occurred, but renal, liver, and bone biochemistry remained normal. Patients in the supplementation group had slightly higher leptin levels at the end of the study than controls. We identified six individuals as "responders" with an improved glycosylation pattern (decreased G0/G2 ratio, P < 0.05). There was a negative relationship between G0/G2 ratio and leptin receptor sOb-R in the supplementation group (P < 0.05). CONCLUSION: Temporary low-dose galactose supplementation in children over 5 y is well tolerated in the clinical setting. It leads to changes in glycosylation in "responders". We consider IgG N-glycan monitoring to be useful for determining individual optimum galactose intake.

D-Galactose High-Dose Administration Failed to Induce Accelerated Aging Changes in Neurogenesis, Anxiety, and Spatial Memory on Young Male Wistar Rats.

The model of accelerated senescence with the prolonged administration of d-galactose is used in anti-aging studies because it mimics several aging-associated alterations such as increase of oxidative stress and decline of cognition. However, there is no standardized protocol for this aging model, and recently some reports have questioned its effectiveness. To clarify this issue, we used a model of high-dose d-galactose on 1-month-old male Wistar rats and studied the hippocampus, one of the most affected brain regions. In one group (n = 10), d-galactose was daily administered intraperitoneally (300 mg/kg) during 8 weeks whereas age-matched controls (n = 10) were injected intraperitoneally with saline. A third group (n = 10) was treated with the same dose of d-galactose and with oral epigallocatechin-3-gallate (EGCG) (2 grams/L), a green tea catechin with anti-oxidant and neuroprotective properties. After treatments, animals were submitted to open-field, elevated plus-maze and Morris water maze tests, and neurogenesis in the dentate gyrus subgranular layer was quantified. There were no significant alterations when the three groups were compared in the number of doublecortin- and Ki-67-immunoreactive cells, and also on anxiety levels, spatial learning, and memory. Therefore, d-galactose was not effective in the induction of accelerated aging, and EGCG administered to d-galactose-treated animals did not improve behavior and had no effects on neurogenesis. We conclude that daily 300 mg/kg of d-galactose administered intraperitoneally may not be a suitable model for inducing age-related neurobehavioral alterations in young male Wistar rats. More studies are necessary to obtain a reliable and reproducible model of accelerated senescence in rodents using d-galactose.

Influence of asafoetida on prevention and treatment of memory impairment induced by d-galactose and NaNO2 in mice.

In Iranian traditional medicine, asafoetida is introduced as a valuable remedy for nervous disorders. Dementia was induced by injection of d-galactose and NaNO2 for 60 consecutive days. Animals were divided into normal control (NC), dementia control (DC), dementia prophylactic (DP), and dementia treated (DT). The learning and memory functions were examined by 1-way active and passive avoidance tests, using a shuttle box device. Avoidance response in training tests and 1 and 3 weeks later was significantly increased in NC, DP, and DT groups compared to the DC group. Step through latency in all groups was significantly greater than the DC group. Total time spent in light room, which shows the memory retention ability, in DP, NC, and DT was significantly greater than the DC group. Our findings indicate that asafoetida could prevent and treat amnesia. These beneficial effects maybe related to some constituent's effectiveness such as ferulic acid and umbelliferone.

A high dose of short term exogenous D-galactose administration in young male rats produces symptoms simulating the natural aging process.

AIMS: D-Galactose (D-gal) induced accelerated senescence has been used to develop an aging model for brain. Previously, long term administration of a wide range of doses has been used for this purpose. In the present study we investigate whether short term administration of a high dose of D-gal in rats induces significant signs and symptoms similar to natural aging. MAIN METHODS: Young rats were injected intraperitoneally with D-gal at a dose of 300 mg/ml/kg for one week. Behavioral analysis for depression and anxiety like symptoms were monitored by forced swim test (FST) and light/dark transition (LDT) test. Assessment of memory was done using the Morris water maze (MWM), passive avoidance test (PAT) and elevated plus maze (EPM) test. Biochemical analysis was done for estimation of antioxidant enzymes and acetylcholinesterase. Determination of brain biogenic amines was performed by HPLC-EC. KEY FINDINGS: Short term administration of D-gal significantly altered behavioral, biochemical and neurochemical responses in rats. D-Gal injected rats exhibited depressogenic and anxiogenic behaviors while memory was also significantly impaired in these rats. Brain lipid peroxidation and superoxide dismutase activity were significantly increased while catalase and glutathione peroxidase decreased. Increased activity of acetylcholinesterase was also exhibited by D-gal injected rats while brain biogenic amines were significantly decreased. Food intake and growth rate were however comparable in both groups. SIGNIFICANCE: Together the behavioral, biochemical and neurochemical impairments following the high dose of D-gal suggest that symptoms similar to natural aging may be developed in rats in as early as one week.