Wound healing process with different photobiomodulation therapy protocols to treat 5-FU-induced oral mucositis in hamsters.

OBJECTIVES: The aim of this study was to analyze the effects of three different Photobiomodulation Therapy (PBMT) protocols in the treatment of 5-fluorouracil-induced oral mucositis in hamsters. DESIGN: 60 hamsters were divided into five groups: group "C", which did not receive oral mucosa scratching, 5-fluorouracil (5-FU) or PBMT; group "Ch", which received anesthesia, superficial oral mucosa scratching and 5-FU (oral mucositis induction); and three groups that received oral mucositis induction and a PBMT protocol: groups ChLI, ChLII and ChLIII that received 0.24 J (one point), 1 J (one point) and 1.2 J (five points of 0.24 J) of energy, respectively. The laser equipment used had λ = 660 nm and 0.04 cm2 of spot area (0.226 cm diameter). The animals were euthanized on days 7 and 10 of the experiment, and their oral mucosas were removed for histological (light microscopy and collagen staining), immunohistochemical (NF-kB and TNF-α), and biochemical (TNF-α, NF-kB and hydroxyproline) analysis. RESULTS: Group ChLI (less energy), showed the most accelerated repair rates and a lower concentration of inflammatory biomarkers than group Ch. Comparing the three PBMT protocols for treatment of 5-FU-induced oral mucositis in hamsters, the one with low energy (0.24 J) showed better results, regarding reduction of inflammatory biomarkers and tissue repair, than the ones with higher energy (1 and 1.2 J).

Effect of Guanxin V in animal model of acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is the most serious and lethal manifestation of coronary heart disease worldwide, presenting extremely high disability and mortality. Our previous studies have shown that Guanxin V (GXV) could significantly improve the cardiac function and the blood flow dynamics, and reduce serum levels of inflammatory factors in AMI rats, thus triggering ventricular remodeling (VR) at post-AMI. METHODS: An in vivo AMI model was established in Syrian hamsters by performing the ligation of the left anterior descending coronary artery. Syrian hamsters were randomly divided into four groups, namely Sham operation group (n = 12), AMI group (n = 12), GXV group (GXV 6 g/Kg/d, n = 12), and Tranilast group (Tra 105 mg/Kg/d, n = 12). Drug intervention was conducted for consecutive 8 weeks. Relative biological indicators were measured in the 4th and 8th week, respectively. RESULTS: Cardiac functions were improved, and the infarcted size and heart weight index were limited in Syrian hamsters of GXV and Tra groups compared with those in AMI group. Furthermore, GXV was able to decrease the number of mast cells and chymase level in Syrian hamsters with AMI. Administration of GXV remarkably inactivated the renin-angiotension-aldosterone system, and alleviated myocardial fibrosis and cardiomyocyte apoptosis, thus slowing down VR at post-AMI. CONCLUSION: GXV slows down the process of VR at post-AMI by reducing chymase level and mast cells number, as well as inactivating the reninangiotension-aldosterone system..

Melatonin Improves Fatty Liver Syndrome by Inhibiting the Lipogenesis Pathway in Hamsters with High-Fat Diet-Induced Hyperlipidemia.

The aim of this study was to investigate the effect of melatonin on hepatic lipid metabolism in hamsters with high-fat diet (HFD)-induced dyslipidemia. Male Syrian hamsters were kept on either a chow control (C) or HFD for four weeks. After four weeks, animals fed the HFD were further randomly assigned to four groups: high-fat only (P), melatonin low-dosage (L), medium-dosage (M), and high-dosage (H) groups. The L, M, and H groups, respectively, received 10, 20, and 50 mg/kg/day of a melatonin solution, while the P and C groups received the ethanol vehicle. After eight weeks of the intervention, results showed that a low dose of melatonin significantly reduced HFD-induced hepatic cholesterol and triglycerides; decreased plasma cholesterol, triglycerides, and low-density lipoprotein cholesterol; and increased plasma high-density lipoprotein cholesterol (p < 0.05). In addition, melatonin markedly decreased activities of the hepatic lipogenic enzymes, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) (p < 0.05), and elevated the relative hepatic carnitine palmitoyltransferase-1α expression in hamsters with HFD-induced hyperlipidemia. Consequently, melatonin reduced activities of the hepatic lipogenic enzymes, ACC and FAS. In summary, chronic melatonin administration improved HFD-induced dyslipidemia and hepatic lipid accumulation in Syrian hamsters with HFD-induced dyslipidemia, which might have occurred through inhibiting the lipogenesis pathway.

The less weight loss due to modest food restriction drove more fat accumulation in striped hamsters refed with high-fat diet.

Food restriction (FR) has been commonly used to decrease body fat, reducing the risk of overweight in humans and animals. However, the lost weight has been shown to be followed by overweight when food restriction ends. It remains uncertain whether the weight loss drives the overweight, or not. In the present study, striped hamsters were restricted by 15%, 30% and 40% of ad libitum food intake for 2 weeks, followed by high-fat refeeding for 6 weeks (FR15%-Re, FR30%-Re and FR40%-Re). The hamsters in FR15%, FR30% and FR40% groups decreased by 21.1%, 37.8% and 50.0% in fat mass (P < 0.01), and 16.8%, 42.8% and 53.4% in leptin levels (P < 0.01) compared with the hamsters fed ad libitum. The FR15%-Re, FR30%-Re and FR40%-Re groups showed 77.0%, 37.2% and 23.7% more body fat than ad libitum group (P < 0.01). The FR15%-Re group showed considerable decreases in gene expression of arcuate nucleus co-expressing proopiomelanocortin (POMC), cocaine - and amphetamineregulated transcript (CART) and the long isoform of leptin receptor (LepRb) in the hypothalamus and of several genes associated with fatty acid transport to mitochondria and ß-oxidation in brown adipose tissue and liver. It suggests that less weight loss is likely to drive more fat accumulation when food restriction ends, in which the impaired function of LepRb, POMC and CART in the brain and fatty acid oxidation in brown adipose tissue and liver may be involved.

The hypolipidemic effects of Tamarindus indica fruit pulp extract in normal and diet-induced hypercholesterolemic hamsters are associated with altered levels of serum proteins.

The hypolipidemic effects of Tamarindus indica fruit pulp extract (Ti-FPE) have been earlier reported but the underlying molecular mechanisms are still uncertain. In this study, hamsters fed with Ti-FPE, both in the absence and presence of high-cholesterol diet, were shown to have significantly reduced levels of serum triglyceride, LDL-C and total cholesterol. The Ti-FPE-fed non-hypercholesterolemic hamsters also showed significant enhanced levels of serum apolipoprotein A1, antithrombin III, transferrin and vitamin D binding protein. In diet-induced hypercholesterolemic hamsters, apolipoprotein A1, antithrombin III and transferrin, which were relatively low in levels, became significantly enhanced when the hamsters were fed with Ti-FPE. These Ti-FPE-fed hypercholesterolemic hamsters also showed significant higher levels of serum vitamin D binding protein. When the different treated groups of hamsters were analyzed for the levels of the four serum proteins by ELISA, similar altered abundance were detected. Ingenuity Pathway Analysis of the Ti-FPE modulated serum proteins singled out "Lipid metabolism, molecular transport, small molecule biochemistry" as the top network. Our results suggest that the hypolipidemic effects of Ti-FPE are associated with alterations of serum proteins that are known to be cardioprotective and involved in the metabolism of lipids. The MS data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD010232.

Evaluation of anti-obesity and lipid-lowering properties of Vaccinium myrtillus leaves powder extract in a hamster model.

Background Vaccinium myrtillus leaves are known to be rich in phenols and have been used in traditional medicine as an antidiabetic remedy. This study evaluated the powder extract of V. myrtillus leaves obtained with the use of L-arginine and myo-inositol for anti-obesity and lipid-lowering potential in hamsters. Methods Standard phytochemical methods were used to determine the total phenolic and total flavonoid contents of the extract. The obesity condition was induced in Syrian hamsters by feeding them with highly palatable fat- and sugar-rich diet (40.3 kcal% fat) for 12 weeks. From the 10th week of diet feeding, the obese hamsters were treated with the powder extract of V. myrtillus leaves (15, 25 and 35 mg/kg/day, respectively) and "Styfimol" (6.2 mg/kg/day of hydroxycitric acid) as a positive control drug. At the end of the treatment period, the biochemical parameters as well as visceral fat mass were determined. Results Vaccinium myrtillus leaves powder extract at 25 and 35 mg/kg/day caused a significant reduction in body weight gain and visceral fat mass in obese hamsters. Serum triacylglycerols, free fatty acids, total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels were also significantly lower. Besides, the hamsters treated with powder extract at 25 and 35 mg/kg/day had the closest intact value ratio of high-density lipoprotein cholesterol and LDL-C compared with positive control animals. Conclusions The results showed that V. myrtillus leaves powder extract is a promising therapeutic agent for the treatment of obesity and obesity-induced diseases.

2-Deoxy-D-glucose, not mercaptoacetate, induces a reversible reduction of body temperature in male desert hamsters (Phodopus roborovskii).

The initiation of torpor is supposed to be related to the availability of metabolic fuels. Studies on metabolic fuel inhibition of glucose by using 2-deoxy-D-glucose (2DG) or fatty acid by mercaptoacetate (MA) in heterothermic mammals produced mixed outcomes. To examine the roles of availability of glucose and fatty acid in the initiation of torpor in desert hamsters (Phodopus roborovskii), we intraperitoneally administrated 2DG and MA to summer-acclimated male hamsters while body temperature (Tb), metabolic rate (MR) and respiratory quotient (RQ) were simultaneously recorded to monitor their thermoregulatory response. 2DG induced a reversible reduction of Tb in desert hamsters both at ambient temperature (Ta) of 23°C and 5°C. At Ta of 23°C, Tb, MR and RQ decreased in a dose-dependent manner with a large Tb-Ta differential (> 6.5°C) and a lowest Tb of 28.0°C which were comparable to those in fasted hamsters. At Ta of 5°C, 2DG-treated hamsters also decreased Tb to the same level as at Ta 23°C, but MR was significantly higher than that at Ta of 23°C at each dose, suggesting doses of 2DG directly affected the hypothalamic Tb set-point. Different from fasted hamsters which maintain normothermic at Ta of 5°C, 2DG-treated hamsters showed a substantial reduction of Tb at Ta 5°C, indicating an overwhelming effect on the thermoregulatory system regardless of Ta. Furthermore, the rapid decrease of Tb and outstretched body posture in 2DG-treated hamsters suggest that the effects of 2DG were not simply mimicking the torpor pathways but that other mechanisms are involved. Interestingly, MA failed to induce a torpor-like state in male desert hamsters. Our results suggest that availability of glucose rather than fatty acid plays an important role for initiation of torpor in desert hamsters.

Dill-normalized liver lipid accumulation, oxidative stress, and low-density lipoprotein receptor levels in high cholesterol fed hamsters.

BACKGROUND: High lipid accumulation in hepatocyte and blood vessels can lead to non-alcoholic fatty liver disease (NAFLD) and heart diseases, respectively. These disorders are the main reasons of mortality in various countries. In this experiment, we evaluated the effect of leaf extracts of Anethum graveolens (AG), also known as Dill, and AG tablet on expression of low-density lipoprotein receptor (LDLR) and liver lipid in hypercholesterolemic hamsters. METHODS: In this experimental study, 36 male golden hamsters were divided into 6 groups: 1) standard diet + 0.5% cholic acid + 2% cholesterol [high cholesterol diet (HCD)], 2) HCD + 100 mg/kg hydroalcoholic extract of Dill, 3) HCD + 200 mg/kg hydroalcoholic extract of Dill, 4) HCD + 100 mg/kg Dill tablet, 5) HCD + 200 mg/kg Dill tablet, 6) chow. At the end of study (30th day), hamsters were anesthetized and blood sample and liver tissue were collected. Biochemical factors and antioxidant parameters were determined. LDLR messenger ribonucleic acid (mRNA) level was measured using real time polymerase chain reaction (RT-PCR). Histopathological change of liver was determined using light microscope. RESULTS: Compared to HCD group, blood lipids (P < 0.0010) and liver enzymes (P < 0.0010) markedly reduced in AG-treated groups. The expression of LDLR did not change significantly in animals which received low dose of hydroalcoholic extract or AG tablet, but it increased in animals receiving high dose of extract or tablet (P < 0.0100). Liver antioxidant significantly increased by AG (P < 0.0010). Liver histopathological changes were normalized by AG. CONCLUSION: AG can significantly increase LDLR gene expression in HCD animals. This study showed that both AG extract and AG tablet had potential antioxidant and hypolipidemic effects in hamsters.

Red algae (Gelidium amansii) hot-water extract ameliorates lipid metabolism in hamsters fed a high-fat diet.

The purpose of this study was to investigate the effects of Gelidium amansii (GA) hot-water extracts (GHE) on lipid metabolism in hamsters. Six-week-old male Syrian hamsters were used as the experimental animals. Hamsters were divided into four groups: (1) control diet group (CON); (2) high-fat diet group (HF); (3) HF with GHE diet group (HF + GHE); (4) HF with probucol diet group (HF + PO). All groups were fed the experimental diets and drinking water ad libitum for 6 weeks. The results showed that GHE significantly decreased body weight, liver weight, and adipose tissue (perirenal and paraepididymal) weight. The HF diet induced an increase in plasma triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol and very-low-density lipoprotein cholesterol levels. However, GHE supplementation reversed the increase of plasma lipids caused by the HF diet. In addition, GHE increased fecal cholesterol, TG and bile acid excretion. Lower hepatic TC and TG levels were found with GHE treatment. GHE reduced hepatic sterol regulatory element-binding proteins (SREBP) including SREBP 1 and SREBP 2 protein expressions. The phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) protein expression in hamsters was decreased by the HF diet; however, GHE supplementation increased the phosphorylation of AMPK protein expression. Our results suggest that GHE may ameliorate lipid metabolism in hamsters fed a HF diet.

EMODIN DOWNREGULATES CELL PROLIFERATION MARKERS DURING DMBA INDUCED ORAL CARCINOGENESIS IN GOLDEN SYRIAN HAMSTERS.

BACKGROUND: Cell-cycle disruption is the major characteristic features of neoplastic transformation and the status of cell-cycle regulators can thus be utilized to assess the prognostic significance in patients with cancer. The PCNA, cyclin D1, CDK4, CDK6 and survivin expression in the buccal mucosa was utilized to evaluate the Emodin efficacy on abnormal cell proliferation during 7,12-dimethylbenz(a)anthracene (DMBA) induced oral carcinogenesis in golden Syrian hamsters. MATERIALS AND METHODS: Topical application of DMBA, three times a week for 14 weeks, on the hamsters' buccal pouches developed well differentiated squamous cell carcinoma. RESULTS: Cyclin D1 and PCNA over-expression and up-regulation of CDK4, CDK6 and survivin were noticed in the buccal mucosa of hamsters treated with DMBA alone. Emodin administration (50mg/kg b.w) orally to hamsters treated with DMBA down-regulated the expression of cell proliferation markers in the buccal mucosa. CONCLUSIONS: The anti-cell proliferative role of Emodin is owing to its modulating efficacy on cell-cycle markers towards the tumor suppression during DMBA induced oral carcinogenesis.

Healing acceleration of oral mucositis induced by 5-fluorouracil with Pistacia atlantica (bene) essential oil in hamsters.

BACKGROUND: Oral mucositis is a common debilitating condition in patients with cancer receiving cytotoxic therapies. This study aimed to evaluate the effects of topical administrations of the essential oil extracted from hull of Pistacia atlantica fruit (bene) on healing of oral mucositis in golden hamsters. METHODS: Forty hamsters with oral mucositis induced by 5-fluorouracil administered on days 0, 5 and 10 and buccal mucosal scratching were randomly divided into four equal groups: group 1 received no additional treatment, group 2 received gel base, and groups 3 and 4 received gels containing 5% and 10% oil, respectively. From day 12, after blood sampling of all animals, a half randomly selected fraction of each group (four half groups) received once-daily topical administration of either gel type (gel base, 5% and 10%) or no treatment (control subgroup) over the buccal pouches for 3 days and the remaining halves received the same treatments for 6 days. On each final day 15 and 18, the corresponding subgroups underwent consecutively the repeated blood sampling, mucosal clinical examination and excision for histopathology. RESULTS: Comparisons on macro- and microscopical oral mucositis scorings demonstrated dose-dependent healing promotion in the subgroups receiving active gels (P < 0.05). The blood samplings revealed the chemotherapy-related pancytopenia with no significant difference among all subgroups on either end point (P > 0.05). CONCLUSIONS: The healing effect of the bene oil could mainly be local and attributed to its antioxidants and fatty acid contents present in non-saponified and saponified fractions, respectively.

Hypocholesterolemic Activity of Curcumin Is Mediated by Down-regulating the Expression of Niemann-Pick C1-like 1 in Hamsters.

We previously demonstrated that curcumin reduces cholesterol absorption in Caco-2 cells through down-regulating Niemann-Pick C1-like 1 (NPC1L1) expression, but the in vivo effect of curcumin on intestinal cholesterol absorption remains unknown. The present study aimed to investigate the effects and mechanisms of curcumin consumption on cholesterol absorption in hamsters. Male hamsters were fed a high-fat diet supplemented with or without curcumin (0.05% w/w) for 12 weeks. Curcumin supplementation significantly decreased serum total cholesterol (TC) (from 6.86 ± 0.27 to 3.50 ± 0.24 mmol/L), triglyceride (TG) (from 5.07 ± 0.34 to 3.72 ± 0.40 mmol/L), and low-density lipoprotein cholesterol (from 2.58 ± 0.19 to 1.71 ± 0.15 mmol/L) levels as well as liver TC (from 11.6 ± 0.05 to 7.2 ± 0.03 mg/g) and TG (from 30.3 ± 0.22 to 25.2 ± 0.18 mg/g) levels (P < 0.05 for all). In contrast, curcumin treatment markedly enhanced fecal cholesterol output (P < 0.01). Moreover, curcumin supplementation down-regulated the mRNA and protein expressions of sterol regulatory element binding protein-2 (SREBP-2) and NPC1L1 in the small intestine (P < 0.05). Our current results indicate that curcumin inhibits cholesterol absorption in hamsters by suppressing SREBP-2 and subsequently down-regulating NPC1L1 expression, which may be responsible for the hypocholesterolemic effects of curcumin.

Development and validation of an Onchocerca ochengi microfilarial hamster model for onchocerciasis drug screens.

BACKGROUND: Onchocerciasis, caused by the parasitic nematode, Onchocerca volvulus afflicts some 37 million people worldwide, and is the second leading infectious cause of blindness globally. The only currently recommended drug for treatment of the disease, ivermectin, is only microfilaricidal and has serious adverse effects in individuals co-infected with high loads of Loa loa microfilariae (mf), prompting the search for new and better drugs. Onchocerciasis drug discovery studies have so far been based on in vivo models using Onchocerca species which are not the closest to O. volvulus, and which may therefore, not adequately mimic the natural infection in humans. Therefore, this study was carried out to develop a better drug screening model for onchocerciasis, based on the use of cow-derived O. ochengi, the closest known relative of O. volvulus. METHODS: Mf of O. ochengi were injected subcutaneously at the nape of Syrian hamsters (Mesocricetus auratus) and BALB/c mice. The skin, and especially the earlobes of the animals were examined for mf 15-31 days after infection. For selected model validation, the hamsters were treated with ivermectin at 150 or 600 µg/kg body weight and examined 30 days after infection for mf. For L. loa studies in hamsters, isolated mf were injected intraperitoneally and animal organs were examined on day 26 for mf. RESULTS: The Syrian hamsters were found to be the more permissive to O. ochengi mf as fully viable mf were recovered from them on day 30, compared to BALB/c mice where such mf were recovered on day 15, but not 30. However, both animals were not permissive to L. loa mf even by day 15. Interestingly, more than 50 % of the total O. ochengi mf recovered were from the earlobes. The number of mf injected was directly proportional to the number recovered. Ivermectin at both concentrations tested completely eliminated the O. ochengi mf from the hamsters. CONCLUSION: This study reveals the Syrian hamster as an appropriate small animal model for screening of novel compounds against O. ochengi, the closest known relative of O. volvulus.

Quantitative Metabolomic Profiling of Plasma, Urine, and Liver Extracts by 1H NMR Spectroscopy Characterizes Different Stages of Atherosclerosis in Hamsters.

Atherosclerosis (AS) is a progressive disease that contributes to cardiovascular disease and shows a complex etiology, including genetic and environmental factors. To understand systemic metabolic changes and to identify potential biomarkers correlated with the occurrence and perpetuation of diet-induced AS, we applied 1H NMR-based metabolomics to detect the time-related metabolic profiles of plasma, urine, and liver extracts from male hamsters fed a high fat and high cholesterol (HFHC) diet. Conventional biochemical assays and histopathological examinations as well as protein expression analyses were performed to provide complementary information. We found that diet treatment caused obvious aortic lesions, lipid accumulation, and inflammatory infiltration in hamsters. Downregulation of proteins related to cholesterol metabolism, including hepatic SREBP2, LDL-R, CYP7A1, SR-BI, HMGCR, LCAT, and SOAT1 was detected, which elucidated the perturbation of cholesterol homeostasis during the HFHC diet challenge. Using "targeted analysis", we quantified 40 plasma, 80 urine, and 60 liver hydrophilic extract metabolites. Multivariate analyses of the identified metabolites elucidated sophisticated metabolic disturbances in multiple matrices, including energy homeostasis, intestinal microbiota functions, inflammation, and oxidative stress coupled with the metabolisms of cholesterol, fatty acids, saccharides, choline, amino acids, and nucleotides. For the first time, our results demonstrate a time-dependent metabolic progression of multiple biological matrices in hamsters from physiological status to early AS and further to late-stage AS, demonstrating that 1H NMR-based metabolomics is a reliable tool for early diagnosis and monitoring of the process of AS.

Hypolipidemic and Antioxidative Effects of Glossogyne tenuifolia in Hamsters Fed an Atherogenic Diet.

Glossogyne tenuifolia (GT) Cassini is a special herbal tea in the Penghu Islands, Taiwan, and has a long history of being used as an antipyretic, detoxifying, and anti-inflammatory remedy in folk medicine among local residents. The aim of this study was to investigate the effect of hot water extracts from GT on oxidative stress and lipid metabolism in animals. Five- to 6-week-old male Syrian hamsters were divided into four groups (n = 14) for different treatments, that is: control group (C), high-fat/cholesterol (HF) group, HF diet containing 0.5% (GT0.5) and 1.5% (GT1.5) GT extracts for 4 weeks. Hamsters fed with 0.5% GT powder as well as 1.5% GT powder exhibited reduced serum total cholesterol (TC), conjugated diene of low-density lipoprotein (LDL), and increased serum antioxidant capacity, but 1.5% GT powder was more potent at lowering serum LDL cholesterol and thiobarbituric acid reactive substance concentrations than 0.5% GT. GT extracts significantly lowered liver triacylglycerol (TG) concentration by diminishing activities of fatty acid synthase (FAS) and glucose-6-phosphate dehydrogenase (G-6-PDH). In addition, fecal excretion of cholesterol and bile acids were increased in GT extract groups. In conclusion, GT extracts increase the antioxidative capacity, decrease serum TC, inhibit the activities of FAS and G-6-PDH, and further reduce liver TG accumulation in hamster fed on atherogenic diets.

Effects of dietary oat proteins on cholesterol metabolism of hypercholesterolaemic hamsters.

BACKGROUND: The aim of present study was to investigate the hypocholesterolaemic effects of oat proteins (OP) in hamsters fed with a hypercholesterolaemic diet. The hamsters were divided into five groups and fed with the experimental diets containing oat, OP, oat ß-glucan (OG), or OP+OG for 30 days. RESULTS: OP and the OG significantly lowered the concentrations of plasma low-density lipoprotein-cholesterol and liver total cholesterol (TC), and increased the excretion of faecal bile acid and TC. Plasma and liver TC in the OP+OG group were significantly lower than those in the OP or OG groups. Both OP and OG increased the activity of liver cholesterol 7α-hydroxylase (CYP7A1), while its activity in the OP+OG group was strongly increased compared with the OP or OG groups. CONCLUSION: These results indicated that dietary OP could improve hypercholesterolaemia, while dietary OP and OG together would have better hypocholesterolaemic effects.

Seco-limonoid derived from Raputia heptaphylla promotes the control of cutaneous leishmaniasis in hamsters (Mesocricetus auratus).

The rational search of novel bioactive molecules against pathogens with immunomodulatory activity is presently one of the most significant approaches to discover and design new therapeutic agents for effective control of infectious diseases, such as the infection caused by Leishmania parasites. In the present study, we evaluated the therapeutic efficacy of the recently characterized immunomodulatory compound 11α,19ß-dihydroxy-7-acetoxy-7-deoxoichangin, a seco-limonoid derived from the bark of Raputia heptaphylla (Pittier) using: (1) peritoneal macrophages and (2) Mesocricetus auratus hamsters infected with Leishmania (V.) panamensis and Leishmania (L.) amazonensis. We observed the ability of this seco-limonoid to induce the effective control of the parasite either in vitro [determining an effective concentration 50 (EC50) of 59 µ m at the infection model] and in vivo (inducing clinical improvement or even cure in infected animals treated compared with the groups of animals treated with vehicle solution or meglumine antimoniate).

Dietary silicon-enriched spirulina improves early atherosclerosis markers in hamsters on a high-fat diet.

OBJECTIVE: The aim of this study was to investigate the effects of dietary silicon-enriched spirulina (SES) on atherosclerosis. METHODS: Hamsters (six per group) on a high-fat (HF) diet received SES or non-enriched spirulina (both at 57 mg/kg body weight) daily. This corresponded to 0.57 mg silicon/kg body weight daily. RESULTS: The HF diet induced dyslipidemia, insulin resistance, oxidative stress, and vascular dysfunction. Compared with the HF group, SES attenuated increases of lipemia and prevented insulin resistance (IR) (P = 0.001). SES protected against oxidative stress through a reduction of heart (P = 0.006) and liver (P < 0.0001) nicotinamide adenine dinucleotide phosphate-oxidase activity and by sparing the activity of superoxide dismutase (P = 0.0017) and glutathione peroxidase (P = 0.01861). SES decreased inflammation, lowering tumor necrosis factor-α (P = 0.0006) and interleukin-6 levels (P = 0.0112), decreasing polymorphonuclear cells and preventing nuclear factor-κB activity (P = 0.0259). SES corrected plasma level of monocyte chemoattractant protein-1 (P = 0.0380), which was increased by the HF diet. Finally, SES supplementation prevented vascular and endothelial functions assessed respectively by the contractile response to the agonist phenylephrine and the relaxation induced by acetylcholine. CONCLUSION: SES protects against metabolic imbalance, inflammation, oxidative stress, and vascular dysfunction induced by an HF diet, and could prevent the atherogenic processes. Synergistic effects between spirulina and silicon were observed.

Dietary Plant Sterol Esters Must Be Hydrolyzed to Reduce Intestinal Cholesterol Absorption in Hamsters.

BACKGROUND: Elevated concentrations of LDL cholesterol are associated with the development of atherosclerosis and therefore are considered an important target for intervention to prevent cardiovascular diseases. The inhibition of cholesterol absorption in the small intestine is an attractive approach to lowering plasma cholesterol, one that is addressed by drug therapy as well as dietary supplementation with plant sterols and plant sterol esters (PSEs). OBJECTIVE: This study was conducted to test the hypothesis that the cholesterol-lowering effects of PSE require hydrolysis to free sterols (FSs). METHODS: Male Syrian hamsters were fed atherogenic diets (AIN-93M purified diet containing 0.12% cholesterol and 8% coconut oil) to which one of the following was added: no PSEs or ethers (control), 5% sterol stearate esters, 5% sterol palmitate esters (PEs), 5% sterol oleate esters (OEs), 5% sterol stearate ethers (STs; to mimic nonhydrolyzable PSE), or 3% FSs plus 2% sunflower oil. The treatments effectively created a spectrum of PSE hydrolysis across which cholesterol metabolism could be compared. Metabolic measurements included cholesterol absorption, plasma and liver lipid concentration, and fecal neutral sterol and bile acid excretion. RESULTS: The STs and the PEs and SEs were poorly hydrolyzed (1.69-4.12%). In contrast, OEs were 88.3% hydrolyzed. The percent hydrolysis was negatively correlated with cholesterol absorption (r = -0.85; P < 0.0001) and positively correlated with fecal cholesterol excretion (r = 0.92; P < 0.0001), suggesting that PSE hydrolysis plays a central role in the cholesterol-lowering properties of PSE. CONCLUSIONS: Our data on hamsters suggest that PSE hydrolysis and the presence of FSs is necessary to induce an optimum cholesterol-lowering effect and that poorly hydrolyzed PSEs may lower cholesterol through an alternative mechanism than that of competition with cholesterol for micelle incorporation.

Water-insoluble fiber-rich fraction from pineapple peel improves intestinal function in hamsters: evidence from cecal and fecal indicators.

Pineapple peel, a byproduct of agricultural processing, contains high levels of water-insoluble fiber-rich fraction (WIFF) (~42%, wt/wt). Our previous work has demonstrated that cellulose, hemicellulose (xylan and xyloglucan), and pectic substances are the major polysaccharides of pineapple-peel WIFF. Based on its chemical composition and unique characteristics, we hypothesized that daily consumption of WIFF would improve intestinal function in hamsters. Male Golden Syrian hamsters were fed a diet supplemented with either 5% cellulose or various amounts of WIFF (2.5%, 5%, or 10%). Activities of fecal bacterial enzymes, short-chain fatty acid concentrations, and microbial number in the cecal content, and also biochemical indicators in the cecal and feces of hamsters, were evaluated in all groups. The supplementation of WIFF in a diet at a level of 2.5% significantly (P < .05) decreased the daily fecal ammonia output; shortened the gastrointestinal transit time; reduced the activities of ß-D-glucosidase, ß-D-glucuronidase, mucinase, and urease in feces; and also enhanced the total amounts of short-chain fatty acid in the cecal content and the growth of gut microflora such as Lactobacillus spp and Bifidobacterium spp. These results indicate that WIFF could improve cecal ecosystem function of hamsters by reducing the toxic compounds excreted by intestinal microflora. Therefore, pineapple-peel WIFF could be a promising candidate for a functional ingredient beneficial to human intestinal function and health.