MetS In Rats Research Articles

Prospects of сomplex pharmaceutical composition application for pharmacological correction of metabolic syndrome

Metabolic syndrome (MetS) is a symptomatic complex characterized by insulin resistance, impaired prooxidant-antioxidantbalance of the body with the development of subchronic inflammation, and dyslipidemia. The aim of the study is to investigate the effect of a complex pharmaceutical composition (CPC) (antioxidants and metabolitotropic agents), which is widely used in medical practice in Ukraine as a multivitamin complex, on experimental metabolic syndrome in rats. The effectof CPC on the correction of experimental MetS in rats, induced by a high content of carbohydrates and fats in the diet, was assessed. MetS in rats was characterized by a decrease in the sensitivity of cells to insulin, increased glucose content, and aviolation of its utilization, prooxidant-antioxidant disbalance. The results of the conducted studies indicate the positive effect of CPC, which contains ethyl esters of omega-3 acids, vitamin E, coenzyme Q10, zinc, vitamin A, biotin, and selenium, on the sensitivity of cells to insulin, glucose utilization, duration of hyperglycemia and indicators of free radical oxidation processes and antioxidant defense systems in rats with experimental MetS. These results prove the feasibility of using CPC to correct metabolic syndrome.

Correlation of Metabolic Syndrome with Redox Homeostasis Biomarkers: Evidence from High-Fat Diet Model in Wistar Rats.

Metabolic Syndrome (MetS) is an extremely complex disease. A non-balanced diet such as high-fat diet (HFD) induces metabolic dysfunction that could modify redox homeostasis. We here aimed at exploring redox homeostasis in male Wistar rats, following 8 weeks of HFD, correlating the eventual modification of selected biomarkers that could be associated with the clinical manifestations of MetS. Therefore, we selected parameters relative to both the glucose tolerance and lipid altered metabolism, but also oxidative pattern. We assessed some biomarkers of oxidative stress i.e., thiols balance, lipid peroxidation and antioxidant barriers, via the use of specific biochemical assays, individuating eventual cross correlation with parameters relative to MetS through a Principal Component Analysis (PCA). The present study shows that 8 weeks of HFD induce MetS in rats, altering glucose and lipid homeostasis and increasing visceral adipose tissue, but also impairing the physiological antioxidant responses that could not counteract the oxidative stress condition. Crucially, cross-correlation analysis suggested that the assessment of specific oxidative stress parameters reported here can provide information comparable to the more widely acquired biomarkers of Mets such as glucose tolerance. Lastly, hepatic steatosis in association with the oxidative stress condition was also highlighted by histological analysis. This research will elucidate the fundamental impact of these oxidative stress parameters on MetS induced in the HFD rat model, tracing paths for developing prevention approaches.

Hongqu Rice Wines Ameliorate High-Fat/High-Fructose Diet-Induced Metabolic Syndrome in Rats.

This study evaluated the possible protective impact of different vintages of Hongqu rice wines on metabolic syndrome (MetS) in rats induced by high-fat/high-fructose diet (HFFD). Rats were randomly divided into six groups and treated with (a) basal diet (13.9kJ/g); (b) HFFD (20.0% w/w lard and 18.0% fructose, 18.9kJ/g) and (c-f) HFFD with 3-, 5-, 8- and 15-year-aged Hongqu rice wines (9.96ml/kg body weight), respectively, at an oral route for 20weeks. Hongqu rice wines could alleviate HFFD-induced augment of body weight gain and fat accumulation, and the release of pro-inflammatory cytokines. Glycolipid metabolic abnormalities caused by HFFD were ameliorated after Hongqu rice wines consumption by lowering levels of fasting insulin, GSP, HOMA-IR, AUC of OGTT and ITT, and lipid deposition (reduced contents of TG, TC, FFA and LDL-C, and elevated HDL-C level) in the serum and liver, probably via regulating expressions of genes involving in IRS1/PI3K/AKT pathway, LDL-C uptake, fatty acid β-oxidation, and lipolysis, export and synthesis of TG. In addition, concentrations of MDA and blood pressure markers (ANG-II and ET-1) declined, and activities of antioxidant enzymes (SOD and CAT) were improved in conditions of Hongqu rice wines compared to those in the HFFD group. Eight-year-aged Hongqu rice wine produced a more effective effect on alleviating HFFD-caused MetS among different vintages of Hongqu rice wines. To sum up, Hongqu rice wines exhibited ameliorative effects on HFFD-induced MetS in rats based on antiobesity, antihyperlipidemic, antihyperglycemic, antioxidant, anti-inflammatory and potential antihypertensive properties.

Athrixia phylicoides tea infusion (bushman tea) improves adipokine balance, glucose homeostasis and lipid parameters in a diet-induced metabolic syndrome rat model

BackgroundCentral obesity and insulin resistance are associated with metabolic syndrome (MetS) which is aggravated by diet and sedentary lifestyle. Athrixia phylicoides (AP) is reported by rural communities to have medicinal benefits associated with MetS such as obesity and type 2 diabetes. This study was aimed to investigate the effects of AP on diet-induced MetS in Wistar rats to validate its ethnopharmacological use.MethodsAP was profiled for phytochemicals by LC-MS. After induction of MetS with high energy diet (HED), 30 male rats were divided into five treatment groups (n = 6): normal diet control, HED control, HED + AP 50 mg/Kg BW, HED + AP 100 mg/Kg BW and HED + 50 mg/Kg BW metformin. The rats were treated daily for 8 weeks orally after which weight gain, visceral fat, total cholesterol, free fatty acids (FFAs) and adipokine regulation; leptin: adiponectin ratio (LAR) were assessed. Also, glucose homeostatic parameters including fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glucose transporter 4 (GLUT 4), insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were determined.ResultsFindings showed that AP was rich in polyphenols. The HED control group showed derangements of the selected blood parameters of MetS. AP reversed diet-induced weight gain by reducing visceral fat, total blood cholesterol and circulating FFAs (p ≤ 0.05). Treatment with AP improved adipokine regulation depicted by reduced LAR (p<0.05). Treatment with AP improved parameters of glucose homeostasis as demonstrated by reduced FBG and HOMA-IR (p ≤ 0.05) and increased GLUT 4 (p<0.05).ConclusionAthrixia phylicoides tea infusion was shown to possess anti-obesity and anti-inflammatory properties, improved glucose uptake and reduce insulin resistance in diet-induced MetS in rats which could be attributed to its richness in polyphenols. Therefore, AP could have potential benefits against type 2 diabetes and obesity which are components of MetS validating its ethnopharmacological use.

Icariin ameliorates metabolic syndrome-induced benign prostatic hyperplasia in rats

Metabolic syndrome (MetS) is an immense health issue that causes serious complications in aging males including BPH. Icariin (ICA) is a flavonol glycoside that exerts a plethora of pharmacological effects. The present investigation tested the potential of ICA to ameliorate benign prostatic hyperplasia (BPH) induced by MetS in rats. Animals were allocated to 5 groups in which the first and second groups were kept on water and regular food pellets. MetS was induced in the third, fourth, and fifth groups by keeping the animals on high fructose and salt diets for twelve consecutive weeks. These groups were given vehicle, ICA (25 mg/kg), and ICA (50 mg/kg), respectively. MetS was confirmed by an increase in rats' weight, accumulation of visceral fat, insulin resistance, and dyslipidemia. This was accompanied by manifestation of BPH including increased prostate weight, prostate index, and histopathological alterations. Treating the animals with both doses of ICA significantly ameliorated the increase in weight and index of the prostate as well as altered prostate histopathology. In addition, ICA significantly decreased cyclin D1 expression, upregulated Bax, and downregulated Bcl2 mRNA expression. ICA prevented lipid peroxidation, reduced glutathione depletion, and catalase exhaustion, which further lowered markers of prostate inflammation such as interleukin-6 and tumor necrosis factor-α. Moreover, ICA prevented the decrease in prostate content of phosphorylated 5'-adenosine monophosphate (AMP)-activated protein kinase (pAMPK). In conclusion, ICA protects against MetS-induced BPH. This is due to its antiproliferative, proapoptotic, antioxidant, and anti-inflammatory activities as well as the activation of AMPK.

A Nano-Pharmaceutical Formula of Quercetin Protects from Cardiovascular Complications Associated with Metabolic Syndrome.

Metabolic syndrome (MetS) is closely associated with the development of cardiovascular diseases. We recently developed a nano-preparation of the flavonoid quercetin (QU) in a self-nanoemulsifying drug delivery system (SNEDDS). The latter comprised a mixture composed of pumpkin seed oil, D-α-Tocopherol polyethylene glycol 1,000 succinate and polyethylene glycol. The QU SNEDDS preparations exhibited a considerably higher bioavailability compared with the standard quercetin suspension. Here, we investigated whether the quercetin loaded SNEDDS could offer better protection compared with the standard formulation against cardiovascular complications of MetS in rats. MetS was induced by high fructose, high salt and high fat diet for 12 weeks while the nano-preparation or the standard suspension of quercetin was orally administered for the last 6 weeks. Compared to little effect for the standard quercetin suspension (MQ), the treatment of MetS rats with the quercetin loaded SNEDDS (MNQ) virtually abolished the depressant effect of MetS on contractility index (control, 114 ± 4; MetS, 92 ± 3; MQ, 100 ± 2; MNQ, 114 ± 6 1/s) and rate of rise in left ventricular pressure (dP/dtmax) (control, 8,171 ± 274; MetS, 6,664 ± 135; MQ, 6,776 ± 108; MNQ, 7,498 ± 303 mmHg/s). Likewise, the prolongation by MetS of electrocardiographic markers of arrhythmogenesis (QTc, JT, and Tpeak-to-Tend intervals) and concomitant rises in dicrotic notch pressure were preferentially reversed by quercetin nano-preparation. On the other hand, the rises in the isovolumic relaxation constant (Tau, denotes diastolic dysfunction), blood pressure, pulse pressure, and difference between systolic and dicrotic pressure (SDP difference) were equally improved by the two preparations of quercetin. Additionally, no differences were noted in the ability of the two quercetin preparations in abrogating the elevated oxidative (MDA) and inflammatory (TNFα) markers in cardiac tissues of MetS rats. Histopathological, microscopical signs of necrosis, inflammatory cell infiltration, and vascular congestion in MetS hearts were more markedly inhibited by the nano-preparation, compared with the standard preparation of quercetin. In conclusion, the quercetin loaded SNEDDS is evidently more advantageous than the standard preparation of the drug in alleviating functional and histopathological manifestations of cardiac damage incited by MetS.

Pleiotropic ameliorative effects of ellagitannin geraniin against metabolic syndrome induced by high-fat diet in rats.

Metabolic syndrome (MetS), a multiplex risk factor for cardiovascular disease and type 2 diabetes, is increasingly prevalent worldwide. Ellagitannin geraniin, a polyphenol found in the rind of rambutan (Nephelium lappaceum), has demonstrated therapeutic effects against metabolism dysfunction. The aim of this study was to characterize the metabolic effects and possible mechanism of geraniin in rats with MetS induced by a high-fat diet (HFD). MetS was induced in Sprague Dawley rats on an HFD, followed by a daily oral gavage of geraniin (25 mg/kg) for 4 wk. The outcomes of geraniin-treated rats were compared with those of untreated rats on either a control diet or an HFD and with rats with MetS treated with metformin on a daily basis (200 mg/kg). The supplementation of geraniin ameliorated multiple metabolic abnormalities caused by HFD, including hypertension, impaired glucose and lipid metabolism, ectopic fat deposition in the visceral fat and liver, and disturbed antioxidant mechanism and inflammatory response. The benefits conferred by geraniin were comparable to metformin. Transcriptomic analysis revealed a profound influence of geraniin on the hepatic expression profiles. The lipid and steroid metabolic processes that were aberrantly activated by HFD were suppressed by geraniin. Based on the differential transcriptomes, geraniin also exerted a significant modulatory effect on the expression of mitochondrial genes, potentially influencing the mitochondrial activity and leading to the observed beneficial effects. Geraniin supplementation mitigated metabolic anomalies of MetS in rats, making it an attractive drug candidate for further investigation.

Crocin prevents metabolic syndrome in rats via enhancing PPAR-gamma and AMPK.

Metabolic syndrome (Mets) is a major health hazard. The syndrome is strongly linked to cardiovascular disease. The objective of the current study was to address whether or not crocin could protect against experimentally-induced MetS in rats as well as the possible underlying mechanisms. Animals were allocated into 4 groups. The first one served as control and was kept on regular food pellets and drinking water. The other three groups were subjected to experimental MetS. Induction of MetS was achieved by keeping rats on food pellets containing 3% NaCl; and drinking water enriched with 10% fructose. The first and second groups were daily gavaged with saline. The third and fourth groups were daily administered crocin 5 and 10 mg/kg, respectively. The treatment continued for 12 consecutive weeks. Crocin significantly reduced body weight gain and adiposity index as compared to MetS group. Also, crocin protected against the occurrence of hyperglycemia and insulin resistance as indicated by controlled values of HOMA-IR. Crocin protected against MetS-induced dyslipidemia as well as the rise blood pressure. These beneficial effects were accompanied by enhanced serum levels of PPARγ & AMPK and inhibited serum levels of IL-6 and TNF-α. In conclusion, crocin protects against experimentally-induced MetS. This can be attributed, at least partly, to activation of PPARγ and AMPK as well as inhibiting inflammation.

Early insulin resistance is associated with alterations in gut permeability and microbial activity in rats fed a moderately westernized diet

AbstractIn Western societies, unbalanced diets may lead to intestinal allostatic stress, with microbial dysbiosis and alteration of the gut barrier function. These local modifications may induce a low-grade inflammation via endotoxemic process, which contribute to systemic alterations clustering into the metabolic syndrome (MetS) and increasing the risk of cardiovascular diseases and type 2 diabetes. We investigated the sequence of events initiating the MetS in rats challenged with a diet that differed moderately from the dietary guidelines, regarding the proportions and nature of energy, carbohydrates, lipids and fibre.Male Wistar rats (265 g upon arrival) were with either a standard diet (Con, n = 10, 3730 kcalkg, 4.0% lipids, 6.3% sucrose, 58.0% starch, 5.0% fibre) or a westernized induction diet (Ind, n = 10, moderately enriched in energy (4120 kcal/kg), lipid (24.0%), and sugars (15%, half sucrose-half fructose), and low in starch (25.5%) and fibre (1.25%). An oral glucose tolerance test (OGTT) was performed after 3 weeks. Rats were euthanized after a further week for body composition and collection of caecum content and tissue samples. LPS-binding protein (LPS-BP) was assayed in plasma; ileum and colon samples were used for measurement of wall barrier function (using Ussing chambers) and microbial activity was assessed in caecum (enzymes and metabolites).Body weight did not differ between Con and Ind groups at any time, as well as the absolute masses and proportions of visceral adipose tissue and liver. Fasting triglyceride, glucose, insulin and LPS-BP concentrations, HOMA index and glucose AUC during the OGTT were similar in both groups. When compared to the Con group, Ind rats showed significantly higher risk markers, i.e.: (1) Insulin AUC (x2); (2) Hepatic triglyceride content (x2.8); (3) Wall permeability at both the para- and transcellular levels (x2.6 and 4.3, respectively) in the ileum (but not in the colon). In the caecum, H2S absolute and relative amounts were twice higher in the Ind group, in relation with 2–3-fold increases in specific and total activities of microbial cysteine desulfhydrase and proteases.Multiple dietary changes mimicking a moderately westernized diet induced an increased ileal permeability and changes in the caecal microbial activity, without evidence of endotoxemia. These perturbations were associated with detrimental rupture of homeostasis at both the splanchnic (hepatic steatosis) and systemic (insulin resistance) levels. In this realistic model, these alterations preceded the occurrence of clinical markers of the MetS (obesity and elevated plasma concentrations of glucose and triglyceride).

The effects of l-Carnosine on development of metabolic syndrome in rats

AimsThe prevalence of metabolic syndrome (MetS) is increasing in several countries. The MetS is characterized by the occurrence of at least three of the following risk factors: decreased high-density lipoprotein cholesterol, increased blood pressure, raised fasting blood glucose, elevated triglycerides, and abdominal obesity. There is a growing evidence of the role of l-carnosine in improving lipid profile and enhancement of the antioxidant activity. However, the effects of l-carnosine on development of MetS are unknown. Main methodsMale Wistar rats were randomly assigned to receive either; conventional diet (control), high-fat high-carbohydrate diet (HFHCD), l-carnosine and conventional diet (L-Car), or l-carnosine and high-fat high-carbohydrate diet (HFHCD and L-Car) for 16 weeks. Central obesity, systolic blood pressure, lipid profile, glucose hemostasis, levels of leptin and adiponectin were evaluated on week 16. Key findingsRats that received HFHCD for 16 weeks showed MetS phenotype such as central obesity, increased blood pressure and glucose, as well as an altered lipid profile (P < 0.05). l-Carnosine supplementation to MetS rats significantly reduced abdominal obesity, blood pressure and glucose, and normalized total cholesterol and low density lipoprotein cholesterol levels (P < 0.05). Insulin, leptin and adiponectin concentrations were not affected by l-Carnosine (P > 0.05). Significancel-carnosine has beneficial effects on ameliorating the manifestations of MetS in rats.

Protective Effects of Olea europaea Fruit Extracts on Metabolic Disorders Associated With Sucrose-Induced Metabolic Syndrome in Rats

Background: Metabolic syndrome (MetS) increases the risk of diabetes. Olea europaea fruit exerts protective effects on metabolic disorders. Therefore, the aim of the present study was to investigate the effect of O. europaea fruit extracts on sucrose-induced MetS in rats. Methods: Male adult Wistar rats (200±50 g, n=32) were randomly divided into four groups (n=8) consisting of control group, untreated sucrose group (sucrose 50% in drinking water for 10 weeks), sucrose plus aqueous extract of O. europaea fruit treated group (200 mg/kg) and sucrose plus hydroalcoholic extract of O. europaea fruit treated group (200 mg/kg) by gavage for 2 weeks. Body weight, serum glucose, insulin, leptin, lipid profile, homeostatic model assessment of insulin resistance (HOMA-IR) and hepatic enzymes were measured. Data were analyzed by one-way analysis of variance (ANOVA, SPSS, 16.0). P&lt;0.05 was regarded as significance level. Results: The aqueous extract exhibited higher protective effects on serum glucose, insulin and HOMA-IR than hydroalcoholic extract (P&lt;0.05). Body weight, serum glucose, leptin (P&lt;0.01), insulin, triglyceride, very-low-density lipoprotein cholesterol (VLDL-C), HOMA-IR, alkaline phosphatase (ALP), (P&lt;0.001) and aspartate aminotransferase (AST) (P&lt;0.05) significantly elevated but high-density lipoprotein cholesterol (HDL-C) (P&lt;0.05) decreased in the sucrose group. Aqueous extract of O. europaea fruit significantly improved blood glucose, triglyceride, VLDL-C (P&lt;0.01), insulin, HOMA-IR, ALP (P&lt;0.001), body weight, AST and leptin (P&lt;0.05) levels. Hydroalcoholic extract of O. europaea fruit significantly restored insulin, HOMA-IR (P&lt;0.01), ALP (P&lt;0.001), body weight, leptin, VLDL-C, triglyceride, blood glucose and AST (P&lt;0.05). Conclusion: Our results indicated O. europaea fruit extracts could improve metabolic disorders induced by MetS in the rats.

The Effects of a Modified High-carbohydrate High-fat Diet on Metabolic Syndrome Parameters in Male Rats.

Metabolic syndrome is a cluster of metabolic abnormalities including central obesity, hyperglycemia, hypertension, and dyslipidemia. A previous study has established that high-carbohydrate high-fat diet (HCHF) can induce MetS in rats. In this study, we modified components of the diet so that it resembled the diet of Southeast Asians. This study aimed to determine the effects of this modified HCHF diet on metabolic parameters in rats. Male Wistar rats (n=14) were randomised into two groups. The normal group was given standard rat chow. The MetS group was given the HCHF diet, comprises of fructose, sweetened condensed milk, ghee, Hubble Mendel and Wakeman salt mixture, and powdered rat food. The diet regimen was assigned for a period of 16 weeks. Metabolic syndrome parameters (abdominal circumference, blood glucose, blood pressure, and lipid profile) were measured at week 0, 8, 12, and 16 of the study. The measurement of whole body composition (fat mass, lean mass, and percentage of fat) was performed using dual-energy X-ray absorptiometry at week 0, 8, and 16. Our results indicated that the components of MetS were partially developed after 8 weeks of HCHF diet. Systolic blood pressure, triglyceride, low density lipoprotein cholesterol, fat content, and percentage of fat was significantly higher in the HCHF group compared to normal group (p<0.05). After 12 weeks of HCHF diet, the rats showed significant increases in abdominal circumference, blood pressure, glucose intolerance, and dyslipidemia compared to normal control (p<0.05). In conclusion, MetS is successfully established in male rats induced by the modified HCHF diet after 12 weeks.

Effects of Liraglutide and Vitamin E in Fructose-Induced Metabolic Syndrome in Rats

Background: Metabolic syndrome (MetS) is a growing worldwide health problem. However, there is yet no effective therapy for MetS. The present work investigated the effect of liraglutide, a synthetic glucagon-like peptide-1 and vitamin E on fructose-induced MetS in rats. Summary: Liraglutide (0.3 mg/kg/day) and vitamin E (100 mg/kg/day) were administered either alone or in combination with high fructose-fed male rats for 6 weeks. Fructose-fed rats developed metabolic disorders assessed by visceral fat index, serum glucose, serum insulin, homeostasis model assessment-insulin resistance and serum lipids profile and hepatic disorders assessed by liver index, serum alanine aminotransferase and aspartate aminotransferase and steatohepatitis in histopathology. This study showed that liraglutide, vitamin E and their combination significantly ameliorated the fructose-induced metabolic and hepatic disorders. Key Messages: These results indicate a potential therapeutic benefit of liraglutide and vitamin E combination in prevention of MetS. Their protective effects might rely on their antioxidant effects as well as on the inhibition of tumor necrosis factor-α.

0205 : Exercise training prevents microvascular dysfunction in a rat model of diet-induced metabolic syndrome

Metabolic syndrome (MetS) is associated with increased risk of cardiovascular disease (CVD). One important key feature underlying the pathophysiology of CVD is microvascular dysfunction. Although, exercise training is a well recognized strategy to reduce cardiovascular and metabolic disorders, the impact on MetS induced microvascular dysfunction is poorly described and the underlying mechanisms remain unknown. Thus, the aim of this work was to evaluate the effect of physical activity on microvascular reactivity in a rat model of MetS. Rats were fed with standard (Ctrl group) or high-fat and sucrose diet (HFS group) for 14 weeks. After 6 weeks, HFS rats were randomly assigned into 2 groups: sedentary (HFS) and trained group (HFS-Ex). In vivo endothelial function was evaluated by skin Laser Doppler technique associated to transcutaneous iontophoresis at 06 and 14 weeks. Body weight, metabolic parameters and blood pressure were also measured. High-fat and sucrose diet induced a significant body weight raise accompanied by the increase of serum level of glucose, triglycerides, HDL and LDL-cholesterol. All of these parameters were restored after 4 weeks of exercise training in HFS-Ex group. In addition, skin endothelium-dependent dilation, which was decreased in HFS compared to Ctrl, was prevented by exercise training. This result could be explained by increased level of eNOS expression and phosphorylation on its activation site (ser1177). These results mainly suggest that an exercise training strategy, which is able to partially correct metabolic disorders in a model of MetS in rats, also prevents in vivo microvascular dysfunction.

Allopurinol alleviates hypertension and proteinuria in high fructose, high salt and high fat induced model of metabolic syndrome

Metabolic syndrome (MetS) is a global epidemic associated with great socioeconomic and public health impact. Prevalence of the MetS has been consistently associated with cardiorenal mortality. The objective of this study was to investigate the effect of allopurinol treatment on various components of an established MetS in rats. In a first group, MetS was induced in male Wistar rats by the addition of 10% fructose to drinking water and placing the rats on high-fat and high-salt diet for 12weeks (M). In the second group, MetS was induced for 12weeks plus allopurinol administration (20mg/kg/d) orally for 4weeks starting at week 9 (MA). The third group was control (C) group that received a normal diet. The M group had higher blood pressure (BP) (85.5±3.17 vs 66.1±3.3mmHg) and proteinuria (1.8±0.3 vs 0.59±0.13g/d) compared with the C group. Allopurinol reversed the BP and proteinuria in MA rats to the control level. Allopurinol administration suppressed the low-grade inflammation associated with MetS and reversed the increases in kidney transforming growth factor beta and urine 8-isoprostane acid observed in the MA group to control levels. In addition, allopurinol reduced angiotensin II and angiotensin receptor type 1 levels in the kidney of MA rats compared with the M group. The administration of allopurinol for short term in an established MetS model reduced features of the MetS especially hypertension and proteinuria. Addition ofallopurinol to the therapy of MetS may provide superior means to alleviate hypertension and proteinuria associated with MetS.

Montelukast and irbesartan ameliorate metabolic and hepatic disorders in fructose-induced metabolic syndrome in rats

Metabolic syndrome (MetS) is a global health problem. Elucidation of the role of 5- lipooxygenase/leukotriene pathway and renin angiotensin system in the pathogenesis of MetS suggests a variety of potential therapies worthy of testing. The present work investigated the effect of montelukast, a leukotriene antagonist and/or irbesartan, an angiotensin II-receptor blocker, in the prevention of fructose-induced MetS in rats. Rats were allocated into 9 groups and treated for 6 weeks as follow: normal control; MetS group (received 20% fructose); MetS+montelukast groups (treated with montelukast, 5, 10, and 20mg/kg/day, respectively); MetS+irbesartan groups (treated withirbesartan 15, 30, and 45mg/kg/day, respectively); and MetS+montelukast+irbesartan group (co treated with montelukast 5mg/kg plus irbesartan 15mg/g). Metabolic parameters (visceral fat index, liver index, insulin resistance, and serum lipid profile), oxidative stress markers (malondialdehyde, reduced glutathione, and catalase), and inflammatory mediators (tumor necrosis factor-α, and uric acid) were measured. Expression of caspase-3 in hepatic tissues was detected by immunohistochemistry. Liver injury was evaluated by histopathological examination and serum alanine aminotransferase (ALT). Montelukast, irbesartan, and their combination caused significant attenuation in metabolic and hepatic disorders. Their effect was associated with attenuation of oxidative stress markers, inflammatory mediators, and caspase-3 expression. This study highlighted the protective effects of montelukast and irbesartan against fructose-induced metabolic and hepatic disorders. The protective effect of either drug relies, at least in part, on their antioxidant and antiinflammatory effect, as well as on the reduction of caspase-3 expression in hepatic tissue.

The selective orexin receptor 1 antagonist ACT-335827 in a rat model of diet-induced obesity associated with metabolic syndrome

The orexin system regulates feeding, nutrient metabolism and energy homeostasis. Acute pharmacological blockade of orexin receptor 1 (OXR-1) in rodents induces satiety and reduces normal and palatable food intake. Genetic OXR-1 deletion in mice improves hyperglycemia under high-fat (HF) diet conditions. Here we investigated the effects of chronic treatment with the novel selective OXR-1 antagonist ACT-335827 in a rat model of diet-induced obesity (DIO) associated with metabolic syndrome (MetS). Rats were fed either standard chow (SC) or a cafeteria (CAF) diet comprised of intermittent human snacks and a constant free choice between a HF/sweet (HF/S) diet and SC for 13 weeks. Thereafter the SC group was treated with vehicle (for 4 weeks) and the CAF group was divided into a vehicle and an ACT-335827 treatment group. Energy and water intake, food preference, and indicators of MetS (abdominal obesity, glucose homeostasis, plasma lipids, and blood pressure) were monitored. Hippocampus-dependent memory, which can be impaired by DIO, was assessed. CAF diet fed rats treated with ACT-335827 consumed less of the HF/S diet and more of the SC, but did not change their snack or total kcal intake compared to vehicle-treated rats. ACT-335827 increased water intake and the high-density lipoprotein associated cholesterol proportion of total circulating cholesterol. ACT-335827 slightly increased body weight gain (4% vs. controls) and feed efficiency in the absence of hyperphagia. These effects were not associated with significant changes in the elevated fasting glucose and triglyceride (TG) plasma levels, glucose intolerance, elevated blood pressure, and adiposity due to CAF diet consumption. Neither CAF diet consumption alone nor ACT-335827 affected memory. In conclusion, the main metabolic characteristics associated with DIO and MetS in rats remained unaffected by chronic ACT-335827 treatment, suggesting that pharmacological OXR-1 blockade has minimal impact in this model.

Potential herbal preparations for the prevention of the metabolic syndrome in rats

Metabolic syndrome (MetS) describes a cluster of different metabolic risk factors including obesity, hyperglycaemia, insulin resistance and dyslipidemia. Nutritional supplementation with botanicals that effectively address pathogenic mechanisms, combined with the acceptance and widespread use of botanical supplements by the general public, represents an attractive, novel, and potentially effective approach to the problem. It was the objective of this study to investigate the preventive effects of aqueous extracts Ficus carica L. (FC), Artemisia dracunculus L. (AD), and Hibiscus sabdariffa L. (HS) on risk factors of MetS in rats since these plants have traditionally been used for the treatment of obesity or hyperglycemia. Male Sprague-Dawley rats were fed with a low fat diet, high fat diet (HFD) or HFD + oral treatment of either 50mg/kg or 100mg/kg of each extract or 30mg/kg pioglitazone for six weeks. A range of parameters was evaluated including body weight development, plasma levels of total cholesterol (TC), triglycerides (TG), low-density-lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), adiponectin, leptin, glucose, insulin, atherogenic index (AI) and the coronary risk index (CRI). It was demonstrated that the aqueous extracts of FC, AD and HS have potential positive effects on the lipid profile, most effectively FC and HS.