Male Syrian Hamsters Research Articles

Chemopreventive potential of phenolic compounds in oral carcinogenesis

ObjectiveTo evaluate the chemopreventive potential of phenolic compounds – potassium apigenin, cocoa, catechins, eriocitrin and rosmarinic acid in oral carcinogenesis induced in hamsters by means of the topical application of 7,12-dimethylbenz(a)anthracene(DMBA). Study designAn experimental study at the University of Murcia. Methods50 male Syrian hamsters (Mesocricetus auratus) were divided into five groups of ten: Group I (control group): 0.5% DMBA; Group II: 0.5% DMBA+1.1mg/15ml potassium apigenin; Group III: 05% DMBA+2.5mg/15ml cocoa catechins; Group IV: 0.5% DMBA+6mg/15ml eriocitrin; Group V: 0.5% DMBA+1.3mg/15ml rosmarinic acid. The flavonoids were administered orally. All the animals were sacrificed after 12 weeks. Macroscopic, microscopic and immunohistochemical (PCNA and p53) analyses of the lesions were performed. ResultsAll the groups treated with phenolic compounds showed lower incidences of tumour, greater differentiation and lower scores in the tumour invasion front grading system in comparison with the control group. Potassium apigenin and rosmarinic acid achieved the best results, the former considerably reduced the carcinoma tumour volumes developed and both significantly reduced the intensity and aggression of the tumours. Immunoexpression of PCNA and p53 were significantly altered during DMBA-induced oral carcinogenesis. ConclusionsAnimals treated with phenolic compounds, particularly potassium apigenin and rosmarinic acid, showed a lower incidence of tumours.

1H NMR-based lipidomics of rodent fur: species-specific lipid profiles and SCD1 inhibitor-related dermal toxicity

A method is described that allows noninvasive identification and quantitative assessment of lipid classes present in sebaceous excretions in rodents. The method relies on direct high-field proton NMR analysis of common group lipid protons in deuterated organic solvent extracts of fur. Extracts from as little as 15 mg of fur from rat, mouse, and hamster provided acceptable results on a 600 MHz NMR equipped with a cryogenically cooled proton-observe probe. In rats, sex- and age-related differences in lipid composition are larger than differences in fur collected from various body regions within an individual and much larger than interanimal differences in age- and sex-matched specimens. The utility of this method to noninvasively monitor drug-induced sebaceous gland atrophy in rodents is demonstrated in rats dosed with a stearoyl-CoA desaturase 1 (SCD1) inhibitor. In this model, a 35% reduction in sebum lipids, extracted from fur, was observed. Finally, structural elucidation of cholesta-7,24-dien-3β-ol ester as the most prominent, previously unidentified sebum sterol ester in male Syrian hamsters is described. The utility of this method for drug and cosmetic safety and efficacy assessment is discussed.

Effect of RFRP-3 on reproduction is sex- and developmental status-dependent in the striped hamster (Cricetulus barabensis)

RFamide-related peptides (RFRPs) are orthologous to gonadotropin-inhibitory hormone (GnIH) inhibiting gonadotropin release. There are only two RFRP sequences (RFRP-1 and RFRP-3) encoded in rodents. RFRP-3, which was considered as a hypothetical inhibitor on GnRH, shows a stimulatory effect on the male Syrian and male Siberian hamster in short days. As a dominant rodent pest in northern China farmland, the striped hamster (Cricetulus barabensis) has higher reproductive activities and could act as a model to study the mechanism of reproduction. However, the effect of RFRP-3 on the reproductive activity for the striped hamster is less understood. In the study, we cloned 643 bp RFRP cDNA from the striped hamster hypothalamus, which contained an ORF of 570 bp encoding two RFamide-related peptide (RFRP) sequences: SPAPANKVPHSAANLPLRF-NH2 (C. barabensis RFRP-1) and TLSRVPSLPQRF-NH2 (C. barabensis RFRP-3). We also investigated the expression variation of RFRP mRNA and GnRH mRNA in the hypothalamus from hamsters with different developmental statuses (7-week-, 13-week- and 1.5-year-olds) using FQ-PCR, in which the 13-week-old female individuals were in estrous. The striped hamsters that are 7 weeks and 1.5 years old are non-breeding individuals, and those that are 13-week hamsters have breeding phenomena. The highest hypothalamus RFRP mRNA level was found in breeding males as compared to non-breeding males. Conversely, the lowest RFRP mRNA level in the hypothalamus was observed in breeding females, with no significant level when the breeding females were compared to the 7-week-old individuals. Additionally, the investigation of GnRH expression level showed a declining expression trend across the developmental stages (7-week-, 13-week- and 1.5-year-olds) in both sexes. Significant negative and positive relationships were detected in the 13-week estrous female (r=-0.997, P=0.035) and the 13-week male (r=0.998, P=0.029) striped hamsters respectively, which suggest that RFRP-3 has inhibitory and stimulatory effects on female and male adults respectively. Our results suggest that the effects of RFRP-3 on reproduction are sex- and developmental status-dependent in the striped hamster.

Maintenance of dominance status is necessary for resistance to social defeat stress in Syrian hamsters

Resilience is an active process that involves a discrete set of neural substrates and cellular mechanisms and enables individuals to avoid some of the negative consequences of extreme stress. We have previously shown that dominant individuals show less stress-induced changes in behavior compared to subordinates using a conditioned defeat model in male Syrian hamsters (Mesocricetus auratus). To rule out pre-existing differences between dominants and subordinates, we examined whether 14 days of dominance experience is required to reduce the conditioned defeat response and whether the development of conditioned defeat resistance correlates with defeat-induced neural activation in select brain regions. We paired hamsters in daily 5-min aggressive encounters for 1, 7, or 14 days and then exposed animals to 3, 5-min social defeat episodes. The next day animals received conditioned defeat testing which involved a 5-min social interaction test with a non-aggressive intruder. In separate animals brains were collected after social defeat for c-Fos immunohistochemistry. We found that 14-day dominants showed a decreased conditioned defeat response compared to 14-day subordinates and controls, while 1-day and 7-day dominants did not differ from their subordinate counterparts. Also, the duration of dominance relationship was associated with distinct patterns of defeat-induced neural activation such that only 14-day dominants showed elevated c-Fos immunoreactivity in the ventral medial prefrontal cortex, medial amygdala, and lateral portions of the ventral medial hypothalamus. Our data suggest that resistance to social stress develops during the maintenance of dominance relationships and is associated with experience-dependent neural plasticity in select brain regions.

Connections of the magnocellular medial preoptic nucleus (MPN mag) in male Syrian hamsters. II. The efferents

The magnocellular medial preoptic nucleus (MPN mag) plays a critical role in the regulation of male copulatory behavior in the Syrian hamster. Our study of the afferents are consistent with the hypothesis that the MPN mag receives input from areas in the chemosensory pathway and nuclear groups that contain receptors for gonadal steroids (Wang and Swann, 2006). The goal of the present study is to identify targets of the MPN mag by describing the location of labeled fibers following an injection of biotinylated dextran amine (BDA) into the MPN mag. Our results indicate that targets of the MPN mag include: (1) brainstem nuclei implicated in regulating male mating behavior in other species, such as the periaqueductal gray, deep mesencephalic nucleus, retrorubral field, ventral tegmental area and lateral paragigantocellular nucleus and (2) steroid-concentrating nuclei in the septum, preoptic area and hypothalamus. The lack of projections from the MPN mag to its chemosensory afferents indicate that the connections of the MPN mag with the posterior medial bed nucleus of the stria terminalis, medial and anterior cortical nuclei of the amygdala are unidirectional, and that chemosensory information flows from the medial amygdala and bed nucleus of the stria terminalis (BST) to the MPN mag. The bidirectional nature of the connections between the MPN mag and steroid-concentrating nuclei suggest that the MPN mag may influence the function of a steroid-concentrating network that regulates behaviors. Together these results support the hypothesis that the MPN mag regulates male mating behavior by integrating chemosensory and hormonal signals and relaying this information to brainstem areas that control motor output.

Spontaneous nonneoplastic lesions in control Syrian hamsters in three 24-month long-term carcinogenicity studies.

Information about the incidence of spontaneously occurring, nonneoplastic background findings in Syrian hamsters is essential if Syrian hamsters are to be used for toxicity studies. Male and female Syrian hamsters of the strain Han:AURA from the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM) breeding colony were maintained as control animals for carcinogenicity studies and were examined for the presence of nonneoplastic background findings either when they died or when the study was terminated. The nonneoplastic background lesions observed at an incidence of >50% (high), >25% (moderate), and >10% (low) in either male or female animals or in both sexes in one or more long-term studies are detailed. The results are compared to previous published reports of nonneoplastic, spontaneous background lesions in Syrian hamsters. Background information about the incidence of background lesions in Syrian hamsters on short- and long-term studies is useful to both toxicologists and toxicological pathologists.

Social forces can impact the circadian clocks of cohabiting hamsters

A number of field and laboratory studies have shown that the social environment influences daily rhythms in numerous species. However, underlying mechanisms, including the circadian system's role, are not known. Obstacles to this research have been the inability to track and objectively analyse rhythms of individual animals housed together. Here, we employed temperature dataloggers to track individual body temperature rhythms of pairs of cohabiting male Syrian hamsters (Mesocricetus auratus) in constant darkness and applied a continuous wavelet transform to determine the phase of rhythm onset before, during, and after cohabitation. Cohabitation altered the predicted trajectory of rhythm onsets in 34% of individuals, representing 58% of pairs, compared to 12% of hamsters single-housed as 'virtual pair' controls. Deviation from the predicted trajectory was by a change in circadian period (τ), which tended to be asymmetric-affecting one individual of the pair in nine of 11 affected pairs-with hints that dominance might play a role. These data implicate a change in the speed of the circadian clock as one mechanism whereby social factors can alter daily rhythms. Miniature dataloggers coupled with wavelet analyses should provide powerful tools for future studies investigating the principles and mechanisms mediating social influences on daily timing.

Biochemical profiling and chemopreventive activity of phloretin on 7,12-Dimethylbenz (a) anthracene induced oral carcinogenesis in male golden Syrian hamsters.

Objectives:The present study was designed to examine the chemopreventive effects of phloretin against 7, 12-dimethylbenz (a) anthracene (DMBA) induced buccal pouch carcinogenesis in male golden Syrian hamsters in order to discover resources to improve the traditional medicine.Materials and Methods:Hamsters were divided into four groups of 10 animals each. Group I was served as an untreated control. Group II hamsters were painted with 0.5% DMBA in liquid paraffin on the left buccal pouches three times a week for 14 weeks. Group III hamsters were orally administrated with phloretin at a dose of 40 mg/kg body Weight (b.wt) on days alternate to DMBA application. Group IV hamsters were orally administrated with phloretin alone and served as the drug control. The experiment was terminated at the end of fourteenth week. The experimental animal's tumors were subjected into morphological examination and subsequently screened the pathological changes and estimate the activities of bi-products of lipid peroxidation, antioxidants enzymes and phase I and II detoxification enzyme status.Results:In DMBA alone treated hamster showed increased levels of lipid peroxidation by products, leads to decreased levels of enzymatic and non-enzymatic antioxidants status, activities of phase I and II detoxification enzyme status were altered. Normalized the neoplastic changes, decreased the levels of lipid by products, retain the antioxidants and restored the phase I and II enzymes were observed in phloretin administrated animals during DMBA induced oral carcinogenesis.Conclusion:Phloretin has possible chemopreventive role in which modulating the antioxidant and detoxification enzyme status, thereby retarding DMBA induced buccal pouch carcinogenesis.

Protective microcirculatory and anti-inflammatory effects of heparin on endotoxemic hamsters

OBJECTIVE: Apart from its anticoagulant properties, heparin has vasodilator and anti-inflammatory effects that could assist in the reversal of septic microcirculatory changes. This paper investigates the effects of heparin on endotoxemia-related microcirculatory changes and compares them to those observed with the use of recombinant human activated protein C. METHODS: After skinfold chamber implantation procedures and endotoxemia induction by intravenous Escherichia coli lipopolysaccharide administration (2mg.kg 21 ), male golden Syrian hamsters were treated with intravenous unfractionated heparin (0.2mg.kg 21 ). Intravital microscopy of skinfold chamber preparations allowed quantitative analysis of microvascular variables and venular leukocyte rolling and adhesion. Macrohemodynamic parameters were also analyzed. Endotoxemic hamsters treated with recombinant human activated protein C and non-treated animals served as controls. RESULTS: Heparin decreased lipopolysaccharide-induced leukocyte rolling and arteriolar vasoconstriction; it also increased survival when compared with non-treated animals, while recombinant human activated protein C decreased leukocyte adhesion. Administration of heparin plus recombinant human activated protein C was associated with a significant attenuation of lipopolysaccharide-induced capillary perfusion deficits. CONCLUSIONS: Heparin yields protective effects on endotoxemic animals’ microcirculation. Those benefits were potentiated when heparin was administered in conjunction with recombinant human activated protein C.

Meibomian adenoma in a Syrian hamster (Mesocricetus auratus

A two-year old male Syrian hamster (Mesocricetus auratus) was brought to the Surgery Clinic at the Istanbul University, Veterinary Faculty, Research and Practice Hospital, with a non-healing wound on the right upper eyelid. An ulcerated, bleeding wound was observed and diagnosed as an eyelid mass. The eyelid mass was excised and submitted for histopathological examination, which resulted in a diagnosis of meibomian adenoma. After excision of the mass, the right upper eyelid became deformed and adopted an abnormal shape. The surgical site was examined two weeks later. No abnormality was observed and the appearance of the right eyelid had returned to normal. Although there are many reports on benign tumours such as polyps, adenomas, haemangiomas and papillomas in hamsters, to the authors’ knowledge, this is the first report on a meibomian adenoma in a Syrian hamster which was resolved by surgery.

Consumption of Purple Sweet Potato Affects Post-Translational Modification of Plasma Proteins in Hamsters

A high level of intake of vegetables is strongly associated with the prevention of chronic diseases. Because post-translational modifications (PTMs) have been shown to be the important biomarkers of the change in physiological functions, this study aimed to explore the changes in PTMs of plasma proteins when purple sweet potato (PSP), a root vegetable, was incorporated into the daily diet. Male Syrian hamsters were maintained on a rice diet (50% rice) or PSP diet (25% rice and 25% PSP) for 12 weeks. Plasma proteins were fractionated by electrophoresis, digested by trypsin, and then separated by nano-liquid chromatography and tandem mass spectrometry. The TurboSequest algorithm was used to identify peptide sequence against the hamster database in Universal Proteins Resource Knowledgebase, and in-house PTM finder programs were used for identification and quantification of PTMs. The results indicated that 95 plasma proteins were identified and 28 PTM sites on 26 of these 95 proteins were affected by consumption of PSP (p < 0.05). Methylation accounted for the largest percentage of affected modifications (35.71%). This study also showed that incorporation of purple sweet potato into the diet significantly lowered blood and liver lipids (p < 0.05). The results of this study provide a basis for prospective studies evaluating the effects of dietary intervention on modifications of proteins.

Effects of Opiate Dependence Through Different Administration Routes on Pulmonary Inflammation and its Severity

BackgroundSerious health problems and socioeconomic consequences of the illicit use of opiates have been proved in both developed and developing societiesObjectivesWe aimed to evaluate" The effects of opiate addiction through different administration routes on pulmonary inflammation and its severity."Materials and MethodsOur experiments were performed on eighteen adult male Syrian golden hamsters which were allocated to one of the three groups (n = 6): control group which did not receive opiate; the first study group were administered oral opiate via stomach tube; and another study group were administered inhaled opiate. After four weeks, all hamsters were anesthetized with diethyl ether and their lung tissues were isolated for pathological assessment.ResultsSevere perivascular inflammation was detected in 33.3% of the samples with oral opiate dependence and 20% of the cases addicted to opiate through inhalation. Also, severe peribronchial inflammation was observed in only 20% of the samples addicted to inhaled opiate and was not found in the other groups. No significant differences were found in the severity of perivascular and peribronchial inflammation across the three groups. Although the mean of total inflammation scale in the subjects with oral opiate dependence (3.00 ± 1.79) was numerically higher than that in the inhaled dependence group (1.40 ± 2.60) and the controls (2.25 ± 1.26), this difference was not statistically significant.ConclusionsAdministration did not influence the appearance or severity of pulmonary inflammation in animal models addicted to opiate.

Adolescent brain maturation is necessary for adult‐typical mesocorticolimbic responses to a rewarding social cue

The interpretation of social cues must change during adolescence in order to promote appropriate social interactions in adulthood. For example, adult, but not juvenile, male Syrian hamsters find female pheromones contained in vaginal sections (VS) rewarding, and only adult hamsters engage in sexual behavior with a receptive female. We previously demonstrated that the rewarding value of VS is both testosterone- and dopamine-dependent. Additionally, VS induces Fos expression throughout the mesocorticolimbic circuit in adult but not juvenile hamsters. In this study, we determined whether or not treatment of juvenile male hamsters with testosterone is sufficient to promote adult-like neural responses to VS. Juvenile and adult male hamsters were gonadectomized and given empty or testosterone-filled subcutaneous capsules for 1 week. Hamsters were then exposed to either clean or VS-containing mineral oil on their nares, and brains were collected 1 h later for immunohistochemistry to visualize Fos and tyrosine hydroxylase immunoreactive cells. Testosterone treatment failed to promote adult-typical patterns of Fos expression in juvenile hamsters; indeed, in some brain regions, juveniles exposed to VS expressed less Fos compared to age-matched controls while, as expected, adults exposed to VS expressed greater Fos compared to age-matched controls. Age-related changes in tyrosine hydroxylase expression were also observed. These data indicate that testosterone cannot activate the adult-typical pattern of Fos expression in response to female social cues in prepubertal males, and that additional neural maturation during adolescence is required for adult-typical mesocorticolimbic responses to female pheromones.

The In vivo Biochemical and Oxidative Changes by Ethanol and Opium Consumption in Syrian Hamsters

Daily consumption of opium and alcohol can make people have many health problems, including coronary artery disease diseases (CAD) which has been found to be the most common cause death in opium addicts. The aim of this study was to investigate the effect of simultaneous consumption of alcohol and opium on the lipid profile and oxidative stress in Syrian golden hamsters. Twenty-four male golden Syrian hamsters were randomly divided into four treatment groups (n=6): 1-control (received normal chow), 2-opium (received 40 mg/kg of opium two times per day), 3-alcohol (received 6.0 g/kg of 30% ethanol two times per day), 4-combination group (received a combination of the above mentioned doses of opium and ethanol). After one month of treatment, hamsters were sacrificed and blood samples were collected. Lipid levels and atherogenic index were markedly increased in the combination group compared with the controls (p < 0.001). Serum alanine aminotransferase (ALT) (p < 0.05), aspartate aminotransferase (AST) (p < 0.05), and gamma-glutamyl transferase (GGT) (p < 0.01), were significantly increased in alcohol-treated group compared with the control animals. The increase in ALT (p < 0.01) and GGT (p < 0.001) levels were more significant in the combination group when compared with the controls. The plasma concentration of malondialdehyde (MDA) was markedly increased in the ethanol (p < 0.01), opium (p < 0.01) and combination groups (p < 0.001) compared with the controls. Glutathione (GSH), nitric oxide (NO) and catalase (CAT) levels as well as superoxide dismutase activity were markedly reduced in the ethanol (p < 0.05), opium (p < 0.05), and combination groups (p < 0.001) compared with the control group. Results of this study clearly showed that opium and ethanol are capable to provoke the oxidative stress when administered alone or in combination. Moreover, combination opium and alcohol increased total cholesterol, LDL-C, TG, VLDL-C, atherogenic index and non-HDL-C levels.

Leptin inhibits the reproductive axis in adult male Syrian hamsters exposed to long and short photoperiod

The aim of the study was to investigate the effects of acute leptin treatment of adult Syrian hamsters exposed to a long (LP, eugonadal males) and short photoperiod (SP, hypogonadal males). Animals were exposed to LP (L:D 14:10) or SP (L:D 10:14) for 10 weeks. Afterwards, both LP and SP hamsters were allocated to a control (SP-C, LP-C) or leptin-treated group (SP 3, SP 10, SP 30 or LP3, LP 10, LP 30). One hour before sacrifice, a single dose of leptin (3, 10 or 30μg/kg) or vehicle was administered (i.p.) to the males. Testis weight, serum and pituitary luteinizing hormone (LH) concentrations, as well as the hypothalamic concentration of gonadotropin-releasing hormone (GnRH) were recorded. Histological analysis of the testis was performed and GnRH concentration in the culture medium of hypothalamic explants was examined. A dramatic regression of testicular weight and histological atrophy of seminiferous tubules, as well as a decrease in serum and pituitary LH concentrations were found in SP males. All doses of leptin significantly reduced serum LH levels and medium GnRH concentrations in both photoperiod groups. Pituitary LH and hypothalamic GnRH concentrations were not affected by leptin. In conclusion, we demonstrated that leptin inhibited the reproductive axis of Syrian male hamsters exposed to LP and SP and fed ad libitum.

The protective effect of recombinant Lactococcus lactis oral vaccine on a Clostridium difficile-infected animal model

BackgroundOral immunization with vaccines may be an effective strategy for prevention of Clostridium difficile infection (CDI). However, application of previously developed vaccines for preventing CDI has been limited due to various reasons. Here, we developed a recombinant Lactococcus lactis oral vaccine and evaluated its effect on a C. difficile-infected animal model established in golden hamsters in attempt to provide an alternative strategy for CDI prevention.MethodsRecombinant L. lactis vaccine was developed using the pTRKH2 plasmid, a high-copy-number Escherichia coli-L. shuttle vector: 1) L. lactis expressing secreted proteins was constructed with recombinant pTRKH2 (secreted-protein plasmid) carrying the Usp45 signal peptide (SPUsp45), nontoxic adjuvanted tetanus toxin fragment C (TETC), and 14 of the 38 C-terminal repeats (14CDTA) of nontoxic C. difficile toxin A (TcdA); and 2) L. lactis expressing secreted and membrane proteins was constructed with recombinant pTRKH2 (membrane-anchored plasmid) carrying SPUsp45, TETC, 14CDTA, and the cell wall-anchored sequence of protein M6 (cwaM6). Then, 32 male Syrian golden hamsters were randomly divided into 4 groups (n = 8 each) for gavage of normal saline (blank control) and L. lactis carrying the empty shuttle vector, secreted-protein plasmid, and membrane-anchored plasmid, respectively. After 1-week gavage of clindamycin, the animals were administered with C. difficile spore suspension. General symptoms and intestinal pathological changes of the animals were examined by naked eye and microscopy, respectively. Protein levels of anti-TcdA IgG/IgA antibodies in intestinal tissue and fluid were analyzed by enzyme-linked immunosorbent assay (ELISA). A cell culture cytotoxicity neutralization assay was done by TcdA treatment with or without anti-TcdA serum pre-incubation or treatment. Apoptosis of intestinal epithelial cells was examined by flow cytometry (FL) assay. Expression of mucosal inflammatory cytokines in the animals was detected by polymer chain reaction (PCR) assay.ResultsAfter the C. difficile challenge, the animals of control group had severe diarrhea symptoms on day 1 and all died on day 4, indicating that the CDI animal model was established in hamster. Of the 3 immunization groups, secreted-protein and membrane-anchored plasmid groups had significantly lower mortalities, body weight decreases, and pathological scores, with higher survival rate/time than the empty plasmid group (P < 0.05). The tilter of IgG antibody directed against TcdA was significantly higher in serum and intestinal fluid of secreted-protein and membrane-anchored plasmid groups than in the empty plasmid group (P < 0.05) while the corresponding titer of IgA antibody directed against TcdA had no substantial differences (P > 0.05). The anti-TcdA serum of membrane-anchored plasmid group neutralized the cytotoxicity of 200 ng/ml TcdA with the best protective effect achieved by anti-TcdA serum pre-incubation. The incidences of TcdA-induced death and apoptosis of intestinal epithelial cells were significantly reduced by cell pre-incubation or treatment with anti-TcdA serum of membrane-anchored plasmid group (P < 0.05). MCP-1, ICAM-1, IL-6, and Gro-1 mRNA expression levels were the lowest in cecum tissue of the membrane-anchored groups compared to the other groups.ConclusionRecombinant L. lactis live vaccine is effective for preventing CDI in the hamster model, thus providing an alternative for immunization of C. difficile-associated diseases.

Central control of circadian phase in arousal-promoting neurons.

Cells of the dorsomedial/lateral hypothalamus (DMH/LH) that produce hypocretin (HCRT) promote arousal in part by activation of cells of the locus coeruleus (LC) which express tyrosine hydroxylase (TH). The suprachiasmatic nucleus (SCN) drives endogenous daily rhythms, including those of sleep and wakefulness. These circadian oscillations are generated by a transcriptional-translational feedback loop in which the Period (Per) genes constitute critical components. This cell-autonomous molecular clock operates not only within the SCN but also in neurons of other brain regions. However, the phenotype of such neurons and the nature of the phase controlling signal from the pacemaker are largely unknown. We used dual fluorescent in situ hybridization to assess clock function in vasopressin, HCRT and TH cells of the SCN, DMH/LH and LC, respectively, of male Syrian hamsters. In the first experiment, we found that Per1 expression in HCRT and TH oscillated in animals held in constant darkness with a peak phase that lagged that in AVP cells of the SCN by several hours. In the second experiment, hamsters induced to split their locomotor rhythms by exposure to constant light had asymmetric Per1 expression within cells of the middle SCN at 6 h before activity onset (AO) and in HCRT cells 9 h before and at AO. We did not observe evidence of lateralization of Per1 expression in the LC. We conclude that the SCN communicates circadian phase to HCRT cells via lateralized neural projections, and suggests that Per1 expression in the LC may be regulated by signals of a global or bilateral nature.

Cholesterol-Lowering Activity of Soy-Derived Glyceollins in the Golden Syrian Hamster Model

Hypercholesterolemia is one of the major factors contributing to the risk of cardiovascular disease (CVD), which is the leading cause of death in developed countries. Consumption of soy foods has been recognized to lower the risk of CVD, and phytochemicals in soy are believed to contribute to the health benefits. Glyceollin is one of the candidate phytochemicals synthesized in stressed soy that may account for many unique biological activities. In this study, the in vivo cholesterol-lowering effect of glyceollins was investigated. Male golden Syrian hamsters were fed diets including (1) 36 kcal% fat diet, (2) 36 kcal% fat diet containing 250 mg/kg diet glyceollins, or (3) chow for 28 days. Hepatic cholesterol esters and free cholesterol, hepatic total lipid content, plasma lipoproteins, fecal bile acid, fecal total cholesterol, and cholesterol metabolism related gene expressions were measured. Glyceollin supplementation led to significant reduction of plasma VLDL, hepatic cholesterol esters, and total lipid content. Consistent with changes in circulating cholesterol, glyceollin supplementation also altered expression of the genes related to cholesterol metabolism in the liver. In contrast, no change in plasma LDL and HDL, fecal bile acid, or cholesterol content was observed. The cholesterol-lowering effect of glyceollins appeared not to go through the increase of bile excretion. These results supported glyceollins' role as novel soy-derived cholesterol-lowering phytochemicals that may contribute to soy's health effects.

Protective effects of [6]-paradol on histological lesions and immunohistochemical gene expression in DMBA induced hamster buccal pouch carcinogenesis.

The search for naturally occurring agents in routinely consumed foods that may inhibit cancer development is of high priority. [6]-Paradol is a pungent phenolic bioactive component from ginger with well- documented health promoting antioxidant, antimutagenic, antigenotoxic and anti-inflammatory properties. However, anticarcinogenic effects have yet to be fully explored. The objectives of the present study were therefore to assess protective effects against 7,12-dimethylbenz(a)anthracene (DMBA) induced buccal pouch carcinogenesis in male golden Syrian hamsters. Oral squamous cell carcinomas developed in the left buccal pouch of hamsters on painting with 0.5% of DMBA, three times in a week. To assess the apoptotic associated gene expressing potential of [6]-paradol, it was orally administered to DMBA treated hamsters on alternate days from DMBA painting for 14 weeks. We observed 100% tumor formation with marked levels of neoplastic changes and altered the expression of apoptotic associated gene (p53, bcl-2, caspase-3 and TNF-α) was observed in the DMBA alone painted hamsters as compared to control hamsters. Oral administration of [6]-paradol at a dose of 30 mg/kg b.wt to DMBA treated animals on alternative days for 14 weeks significantly reduced the neoplastic changes and improved the status of apoptosis associated gene expression. These observations confirmed that [6]-paradol acts as a tumor suppressing agent against DMBA induced oral carcinogenesis. We also conclude that [6]-paradol also effectively enhances apoptosis- associated gene expression in DMBA treated animals.

Curcuma oil ameliorates hyperlipidaemia and associated deleterious effects in golden Syrian hamsters

Essential oil components from turmeric (Curcuma longa L.) are documented for neuroprotective, anti-cancer, anti-thrombotic and antioxidant effects. The present study aimed to investigate the disease-modifying potential of curcuma oil (C. oil), a lipophilic component from C. longa L., in hyperlipidaemic hamsters. Male golden Syrian hamsters were fed a chow or high-cholesterol (HC) and fat-rich diet with or without C. oil (30, 100 and 300 mg/kg) for 28 d. In HC diet-fed hamsters, C. oil significantly reduced plasma total cholesterol, LDL-cholesterol and TAG, and increased HDL-cholesterol when compared with the HC group. Similar group comparisons showed that C. oil treatment reduced hepatic cholesterol and oxidative stress, and improved liver function. Hyperlipidaemia-induced platelet activation, vascular dysfunction and repressed eNOS mRNA expression were restored by the C. oil treatment. Furthermore, aortic cholesterol accumulation and CD68 expression were also reduced in the C. oil-treated group. The effect of C. oil at 300 mg/kg was comparable with the standard drug ezetimibe. Delving into the probable anti-hyperlipidaemic mechanism at the transcript level, the C. oil-treated groups fed the chow and HC diets were compared with the chow diet-fed group. The C. oil treatment significantly increased the hepatic expression of PPARa, LXRa, CYP7A1, ABCA1, ABCG5, ABCG8 and LPL accompanied by reduced SREBP-2 and HMGCR expression. C. oil also enhanced ABCA1, ABCG5 and ABCG8 expression and suppressed NPC1L1 expression in the jejunum. In the present study, C. oil demonstrated an anti-hyperlipidaemic effect and reduced lipid-induced oxidative stress, platelet activation and vascular dysfunction. The anti-hyperlipidaemic effect exhibited by C. oil seems to be mediated by the modulation of PPARa, LXRa and associated genes involved in lipid metabolism and transport.