Synthesis and In Vivo Hypolipidemic Effect of Some N-(Benzoylphenyl)-Carboxamide Derivatives in Triton WR-1339-Induced Hyperlipidemic Rats

A series of N-(benzoylphenyl)-carboxamide derivatives (2a, 2b, 3a, 3b, 4a, 4b, 5a, 5b, 6a and 6b) was prepared with good yields by reacting the corresponding carbonyl chlorides with aminobenzophenones at room temperature. This was followed by evaluating the hypotriglyceridemic and hypocholesterolemic effects of 3b, 5a and 5b. Triton WR-1339 (300 mg/kg) was intraperitoneally administered to overnight-fasted rats to induce hyperlipidemia. Rats were divided into six groups: control, hyperlipidemic, hyperlipidemic plus compounds 3b, 5a and 5b and hyperlipidemic plus bezafibrate. Results showed that after 18 h of treatment at a dose of 15 mg/kg body weight of each of the test compounds, the elevated plasma levels of triglycerides (TG) and total cholesterol (TC) were significantly lowered by compounds 5b and 3b (p < 0.001) and by 5a (p < 0.0001), compared to the hyperlipidemic control group. Compounds 3b and 5a significantly increased levels of high-density lipoprotein cholesterol (HDL-C) by 58 and 71%, respectively. In addition, compounds 3b and 5a caused significant reduction (p < 0.0001) of low-density lipoprotein cholesterol (LDL-C) levels compared to the control group. These results suggest a promising potential for compounds 3b, 5a and 5b as lipid-lowering agents, which may contribute to reducing the risk of atherosclerosis and cardiovascular disease

Tyramine exerts hypolipidemic and anti-obesity effects in vivo

Abstract Obesity and dyslipidemia are conditions often associated with cardiovascular risk, inflammation, oxidative stress, and death. Thus, a new approach has been highlighted to promote research and development of pharmacological tools derived from natural sources. Among the most widely studied groups of substances, polyphenols such as tyramine stand out. This study investigated hypolipidemic and anti-obesity properties of tyramine. Oral toxicity evaluation, models of dyslipidemia and obesity were used. To induce dyslipidemia, Poloxamer-407 (P-407) was administered intraperitoneally. In the hypercholesterolemic and obesity model, specific diet and oral tyramine were provided. After 24h of P-407 administration, tyramine 2 mg/kg (T2) decreased triglycerides (TG) (2057.0 ± 158.5 mg/dL vs. 2838 ± 168.3 mg/dL). After 48h, TG were decreased by T2 (453.0 ± 35.47 vs. 760.2 ± 41.86 mg/dL) and 4 mg/kg (T4) (605.8 ± 26.61 760.2 ± 41.86 mg/dL). T2 reduced total cholesterol (TC) after 24h (309.0 ± 11.17 mg/dL vs. 399.7 ± 15.7 mg/dL); After 48h, 1 mg/kg (T1) (220.5 ± 12.78 mg/dL), T2 (205.8 ± 7.1 mg/dL) and T4 (216.8 ± 12.79 mg/dL), compared to P-407 (275.5 ± 12.1 mg/dL). The treatment decreased thiobarbituric acid reactive substances and nitrite in liver, increased superoxide dismutase, reduced the diet-induced dyslipidemia, decreasing TC around 15%. Tyramine reduced body mass, glucose, and TC after hypercaloric feed. Treatment with 5 mg/L (0.46 ± 0.04 ng/dL) and 10 mg/L (0.44 ± 0.02 ng/dL) reduced plasma insulin (1.18 ± 0.23 ng/dL). Tyramine increased adiponectin at 5 mg/L (1.02 ± 0.02 vs. 0.83 ± 0.02 ng/mL) and 10mg/L (0.96 ± 0.04 ng/mL). In conclusion, tyramine has low toxicity in rodents, has antioxidant effect, reduces plasma triglycerides and cholesterol levels. However, further studies should be conducted in rodents and non-rodents to better understand the pharmacodynamic and pharmacokinetic properties of tyramine

Simvastatin Induces Apoptosis and Suppresses Insulin-Like Growth Factor 1 Receptor in Bile Duct Cancer Cells

BACKGROUND/AIMS: Statins act as antineoplastic agents through the inhibition of cell proliferation. This study sought to demonstrate the effects of statins on extrahepatic bile duct cancer cell apoptosis and to document the changes in protein expression involved in tumor growth and suppression. METHODS: Human extrahepatic bile duct cancer cells were cultured. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine the effect of statins on cell proliferation. Apoptosis was measured by a cell death detection enzyme-linked immunosorbent assay and caspase-3 activity assay, and flow cytometry was used to determine the percentage of cells in each phase of the cell cycle. The protein expression of Bax, Bcl-2, insulin-like growth factor 1 (IGF-1) receptor, extracellular signal-regulated kinase 1/2 (ERK1/2), and Akt was measured by Western blot analysis. RESULTS: Simvastatin suppressed cell proliferation by inducing G1 phase cell cycle arrest in bile duct cancer cells. Furthermore, it induced apoptosis via caspase-3 activation, downregulated the expression of the Bcl-2 protein, and enhanced the expression of the Bax protein. Moreover, simvastatin suppressed the expression of the IGF-1 receptor and IGF-1-induced ERK/Akt activation. CONCLUSIONS: Simvastatin induces apoptosis in bile duct cancer cells, which suggests that it could be an antineoplastic agent for bile duct cancer.

Dislipidemias: ¿qué hay de nuevo? / Dyslipidemia: what's new?

En los últimos años han surgido algunas investigaciones y guías de práctica clínica relacionadas con el diagnóstico y tratamiento de las dislipidemias, que aportaron nuevos conocimientos (y controversias) sobre dicha problemática. En este resumen se describen, en primer lugar, las características de las "nuevas guías" norteamericanas para el manejo del colesterol publicadas a fines de 2013 y se comparan con las recomendaciones tradicionales. En segundo lugar, se analizan los últimos estudios que evaluaron el impacto cardiovascular de otros fármacos hipolipemiantes (ezetimibe y ácido nicotínico) en pacientes en prevención secundaria tratados con estatinas. Finalmente, se mencionan las nuevas drogas hipolipemiantes desarrolladas en los últimos años, como el lomitapide, el mipomersen y los inhibidores de la PCSK9, y se comentan el mecanismo de acción, su eficacia, sus efectos colaterales y los escenarios clínicos en donde podrían utilizarse. (AU)

In recent years, some research and clinical practice guidelines related to the diagnosis and treatment of dyslipidemia, which provided new knowledge (and controversy) about this problem have emerged. In this review, the characteristics of the American "new guidelines" for cholesterol management published by the end of 2013 are described, and they are compared with the traditional recommendations. In addition, recent studies assessing the cardiovascular impact of other lipid-lowering drugs (ezetimibe and nicotinic acid) in patients in secondary prevention treated with statins are analyzed. Finally, new hypolipidemic drugs developed in recent years are mentioned (lomitapide, mipomersen and PCSK9 inhibitors), discussing the mechanism of action, efficacy, side effects and clinical settings where they could be used. (AU)

El ácido nicotínico aumenta el transporte celular de colesterol de las lipoproteínas de alta densidad en pacientes con hipoalfalipoproteinemia / Nicotinic acid increases cellular transport of high density lipoprotein cholesterol in patients with hypoalphalipoproteinemia

Background: Plasma high density lipoproteins (HDL) are involved in reverse cholesterol transport mediated by the scavenger receptor class B type I (SR-BI). Nicotinic acid increases HDL cholesterol levels, even though its specific impact on SR-BI dependent-cellular cholesterol transport remains unknown. Aim: To determine the effect of nicotinic acid on HDL particle functionality in cholesterol efflux and uptake mediated by SR-BI in cultured cells in hypoalphalipoproteinemic patients. Material and Methods: In a pilot study, eight patients with low HDL (≤ 40 mg/dL) were treated with extended release nicotinic acid. HDL cholesterol and phospholipid levels, HDL2 and HDL3 fractions and HDL particle sizes were measured at baseline and post-therapy. Before and after nicotinic acid treatment, HDL particles were used for cholesterol transport studies in cells transfected with SR-BI. Results: Nicotinic acid treatment raised total HDL cholesterol and phospholipids, HDL2 levels as well as HDL particle size. Nicotinic acid significantly increased HDL cholesterol efflux and uptake capacity mediated by SR-BI in cultured cells. Conclusions: Nicotinic acid therapy increases SR-BI-dependent HDL cholesterol transport in cultured cells, establishing a new cellular mechanism by which this lipid-lowering drug appears to modulate HDL metabolism in patients with hypoalphalipoproteinemia.

Ethanolic extract of Casearia sylvestris Sw exhibits in vitro antioxidant and antimicrobial activities and in vivo hypolipidemic effect in rats / Extrato etanólico de Casearia sylvestris Sw apresenta atividade antioxidante e antimicrobiana in vitro e efeito hipolipemiante em ratos

ABSTRACT: The Casearia sylvestris Sw (Flacourtiaceae) is a shrub that occurs in forests of Southern Brazil; its leaves are widely used in folk medicine as a depurative, analgesic, anti-inflammatory and antiulcerogenic agent. The objective of this study was to perform the phytochemical description and to evaluate the pharmacological activities (antimicrobial, antifungal, antioxidant and toxicity) of the ethanolic extract (EE) of C. sylvestris Sw. In addition, we also evaluated the effect of the EE of C. sylvestris Sw on the glucose levels and lipid profile in blood serum of rats submitted to a model of streptozotocin-induced diabetes. Material and Methods: In vitro assay: the detection of chemical groups was done through chemical reactions with the development of color or precipitate and by chromatographic profile; the antioxidant activity was measured by the method of reduction of DPPH free radical (2,2-diphenyl-1-picrylhydrazyl); the Minimum Inhibitory Concentration was evaluated by the broth microdilution method, and the Minimum Bactericide Concentration and the Minimum Fungicide Concentration were performed in Petri dishes; the cytotoxic activity was measured by the Artemia salina test. In vivo assay: diabetic and non-diabetic rats were treated with EE of C. sylvestris Sw (300 mg/kg) for 45 days, and the glycaemia and lipid profile were analyzed. Results: The EE showed a Lethal Dose50 of 724.76 μg.mL-1 and important antioxidant, fungicide and fungistatic activities. The EE showed better antimicrobial activity regarding the microorganisms Staphylococcus aureus, Escherichia coli and Salmonella setubal. Conclusion: The EE of C. sylvestris Sw produces a significant decrease in triglycerides, total cholesterol and VLDL levels without any significant alteration in the glycaemia. The EE of C. sylvestris Sw presents antioxidant and antimicrobial activities and it exhibits a potent hypolipidemic effect.

RESUMO: Casearia sylvestris Sw (Flacourtiaceae) é uma planta comumente encontrada em florestas do sul do Brasil; suas folhas são amplamente utilizadas na medicina popular como depurativa, analgésica, anti-inflamatória e anti ulcerogênica. O objetivo deste estudo foi apresentar uma descrição fitoquímica e da atividade farmacológica (antimicrobiana, antifúngica, antioxidante e toxicidade) do extrato etanólico (EE) da C. Sylvestris Sw. Adicionalmente, procurou-se avaliar o efeito do EE da C. Sylvestris Sw sobre os níveis séricos de glicose e perfil lipídico de ratos submetidos a um modelo de diabetes induzida por estreptozotocina. A detecção de grupos químicos foi realizada por reações químicas de coloração ou precipitação, e também por cromatografia; a atividade antioxidante foi mensurada pelo método de redução do DPPH (2,2-difenil-1-picril-hidrazil); a concentração mínima inibitória foi realizada pela técnica de micro-diluição, e concentração mínima bactericida e concentração mínima fungicida foram realizadas em placa de Petri; enquanto a atividade citotóxica foi conduzida pelo teste da Artemia salina. Nos ensaios in vivo, ratos diabéticos e não-diabéticos foram tratado com EE da C. Sylvestris Sw (300mg/kg) por 45 dias, e os níveis glicêmico e perfil lipídico foram medidos. A dose Letal50 do EE foi de 724.76 μg.mL-1; mostrando importante atividades antioxidante, fungicida e fungistática e melhor atividade antimicrobiana contra Staphylococcus aureus, Escherichia coli e Salmonella setubal. O EE da C. Sylvestris Sw promoveu diminuição significativa nos níveis de triglicerídeos, colesterol total e VLDL; porém sem efeito significativo nos níveis glicêmicos. O EE da C. Sylvestris Sw, além de apresentar atividade antioxidante e antimicrobiana; possui também potente efeito hipolipidêmico.

Hypolipidemic and hypoglycemic effects of Centella asiatica (L.) extract in vitro and in vivo.

In vitro study revealed that pancreatic lipase inhibitory activity of C. asiatica extract was significantly higher than rutin but lower than orlistat, an anti-obesity drug. α-Amylase inhibitory activities of C. asiatica extract and rutin were significantly lower than acarbose, an anti-diabetic drug. Inhibition of α-glucosidase activity by C. asiatica extract, rutin, and acarbose was not different. The in vivo study substantiated the in vitro results. C. asiatica extract (1000 and 2000 mg/4 mL/kg), rutin (1000 mg/4 mL/kg), and orlistat (45 mg/4 mL/kg) significantly decreased plasma glucose, triglyceride and total cholesterol levels in lipid emulsion-induced hyperlipidemic rats at 3 h. However, plasma aspartate aminotransferase and alanine aminotransferase levels did not show significant change. The present work further supports that the C. asiatica extract and its bioactive rutin may help managing hypolipidemic and hypoglycemic effects.

Hypolipidemic and antioxidant activity of aqueous extract of fruit of Withania coagulans (Stocks) Dunal in cholesterol-fed hyperlipidemic rabbit model.

Withania coagulans (family: Solanaceae, English: Indian Cheese Maker, Hindi: Doda Paneer) fruit is known for its ethanopharmacological significance in health care system of India. Diet rich in high-fat is an important risk factor for diabetes, atherosclerosis and macro and microvascular complications. Treatment with aqueous extract of fruit of W. coagulans (aqWC; 250 mg/kg body weight) in cholesterol-fed animals resulted in significant decrease in the levels of total cholesterol, triacylglycerol, low density lipoprotein, tissue lipid content and acetyl CoA carboxylase activity whereas, the level of high density lipoprotein and activity of HMGCoA reductase also recovered partially. Treatment with aqWC also significantly decreased plasma lipid peroxide levels and increased reduced glutathione and superoxide dismutase activities. These results suggest that the aqueous extract of W. coagulans has potent lipid lowering and antioxidant activities.

Evaluation of Sexual Dimorphism in the Efficacy and Safety of Simvastatin/Atorvastatin Therapy in a Southern Brazilian Cohort / Papel do Dimorfismo Sexual na Eficácia e Segurança da Terapia com Sinvastatina ou Atorvastatina em uma Coorte no Sul do Brasil

Background: Dyslipidemia is the primary risk factor for cardiovascular disease, and statins have been effective in controlling lipid levels. Sex differences in the pharmacokinetics and pharmacodynamics of statins contribute to interindividual variations in drug efficacy and toxicity. Objective: To evaluate the presence of sexual dimorphism in the efficacy and safety of simvastatin/atorvastatin treatment. Methods: Lipid levels of 495 patients (331 women and 164 men) were measured at baseline and after 6 ± 3 months of simvastatin/atorvastatin treatment to assess the efficacy and safety profiles of both drugs. Results: Women had higher baseline levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) compared with men (p < 0.0001). After treatment, women exhibited a greater decrease in plasma TC and LDL-C levels compared with men. After adjustment for covariates, baseline levels of TC and LDL-C influenced more than 30% of the efficacy of lipid-lowering therapy (p < 0.001), regardless of sex. Myalgia [with or without changes in creatine phosphokinase (CPK) levels] occurred more frequently in women (25.9%; p = 0.002), whereas an increase in CPK and/or abnormal liver function was more frequent in in men (17.9%; p = 0.017). Conclusions: Our results show that baseline TC and LDL-C levels are the main predictors of simvastatin/atorvastatin therapy efficacy, regardless of sex. In addition, they suggest the presence of sexual dimorphism in the safety of simvastatin/atorvastatin. The effect of sex differences on receptors, transporter proteins, and gene expression pathways needs to be better evaluated and characterized to confirm these observations. .

Fundamento: A dislipidemia é o principal fator de risco para doenças cardiovasculares e as estatinas são efetivas no controle do perfil lipídico. Diferenças sexuais na farmacocinética e farmacodinâmica contribuem para a variação interindividual na eficácia e toxicidade de fármacos. Objetivo: Avaliar a existência de dimorfismo sexual na eficácia e segurança do tratamento com sinvastatina/atorvastatina. Métodos: 495 sujeitos (331 mulheres e 164 homens) tiveram seus níveis lipídicos mensurados antes e após 6±3 meses de tratamento com sinvastatina/atorvastatina para avaliação dos perfis de eficácia e segurança. Resultados: As mulheres apresentaram maiores níveis basais de colesterol total, LDL-C e HDL-C quando comparadas aos homens (p < 0,0001). Após o tratamento, mulheres tiveram uma maior redução dos níveis de colesterol total e de LDL-C que homens. Após ajuste para covariáveis, foi observado que os níveis basais de colesterol total e de LDL-C são responsáveis por cerca de 30% da eficácia (p < 0,001), independentemente do sexo. Mialgia (com ou sem alteração de creatina fosfoquinase - CPK) ocorreu mais frequentemente em mulheres (25,9%) (p = 0,002), enquanto o aumento isolado de CPK e alterações de função hepática foram mais frequentemente observados em homens (17,9%) (p = 0,017). Conclusões: Nossos resultados demonstram que os níveis basais de colesterol total e LDL-C são os maiores preditores da eficácia do tratamento, independente do sexo. Adicionalmente, sugerimos que existe dimorfismo sexual na segurança do tratamento com sinvastatina/atorvastatina. O efeito das diferenças sexuais em receptores, proteínas transportadoras e rotas de expressão gênica devem ser avaliados ...

In vivo Evaluation of Hypolipidemic Potentials of Bacillus Species Isolated from Fermented Locust Bean (Parkia fillicoides Welw) Seeds (Iru).

Aim: Iru is a popular West Africa fermented soup condiment which is also consumed without cooking as snack. This product is mainly fermented by Bacillus species. The hypolipidemic activities of Bacillus spp. isolated from iru have not been documented hence the aim of this study. Place and Duration of Study: Iru sample was bought in an open market in Iworoko-Ekiti, Nigeria and transferred to the Laboratory of the Department of Microbiology, Ekiti State University, Nigeria where other studies were carried out. The study was conducted between January and June, 2012. Methodology: The properties and in vivo hypolipidemic potential of Bacillus species from iru were investigated using standard microbiological and haematological methods. Results: The cell free extracts of the Bacillus spp. did not produce significant inhibition on the selected Gram positive and Gram negative pathogens. Qualitative enzyme screening of the isolates showed all were haemolysin negative. Only B. subtilis was positive to gelatinase while all the isolates produced catalase and lipase. The average weight of the animals after inducement of hyper-cholesterolemia ranged between 60.5g - 95.3g. The amount of serum total cholesterol (TC) in the animals ranged between 124.9 mg/dl – 127.4 mg/dl while that of serum triglycerides (TG), high density protein (HDL) and low density protein (LDL) were 122.5 – 155.3 mg/dl, 10.0 – 15.3 mg/dl and 76.6 – 81.0 mg/dl respectively. The weights of hyper-cholesterolemia induced rats challenged with different species of Bacillus were relatively lower than those in the control group and also differ significantly from the control, at p˂ 0.05. The values of TC, TG, and LDL were highest in the control (saline) group while the values in the treatment group ranged between 121.3 ± 1.5 and 102.3 ± 6.8 mg/dl for TC. The treatment groups recorded lower values of values for TG (104.7 ± 1.6 - 117.4 ± 9.1 mg/dl) and LDL (42.6 ±7.4 - 59.0 ± 10.2 mg/dl) compared to the control. B. subtilis had the highest values of TC but least amount of LDL. TG in all the groups was higher than TC, HDL and LDL. The TC/HDL and the LDL/HDL of the animals in the iru group was higher than the other treatment groups but lower than the control. Conclusion: Compared to the control, hypolipidemic activities of B. lichenliformis was the best followed by B. subtilis. Iru had the least hypo-cholesterolemic effect.

Pleiotropic effects of simvastatin in physically trained ovariectomized rats

This study tested the hypothesis that simvastatin treatment can improve cardiovascular and autonomic functions and membrane lipoperoxidation, with an increased effect when applied to physically trained ovariectomized rats. Ovariectomized rats were divided into sedentary, sedentary+simvastatin and trained+simvastatin groups (n = 8 each). Exercise training was performed on a treadmill for 8 weeks and simvastatin (5 mg/kg) was administered in the last 2 weeks. Blood pressure (BP) was recorded in conscious animals. Baroreflex sensitivity was evaluated by the tachycardic and bradycardic responses to BP changes. Cardiac vagal and sympathetic effects were determined using methylatropine and propranolol. Oxidative stress was evaluated based on heart and liver lipoperoxidation using the chemiluminescence method. The simvastatin-treated groups presented reduced body weight and mean BP (trained+simvastatin = 99 ± 2 and sedentary+simvastatin = 107 ± 2 mmHg) compared to the sedentary group (122 ± 1 mmHg). Furthermore, the trained group showed lower BP and heart rate compared to the other groups. Tachycardic and bradycardic responses were enhanced in both simvastatin-treated groups. The vagal effect was increased in the trained+simvastatin group and the sympathetic effect was decreased in the sedentary+simvastatin group. Hepatic lipoperoxidation was reduced in sedentary+simvastatin (≈21%) and trained+simvastatin groups (≈57%) compared to the sedentary group. Correlation analysis involving all animals demonstrated that cardiac lipoperoxidation was negatively related to the vagal effect (r = -0.7) and positively correlated to the sympathetic effect (r = 0.7). In conclusion, improvement in cardiovascular and autonomic functions associated with a reduction of lipoperoxidation with simvastatin treatment was increased in trained ovariectomized rats.

Biological evaluation of a siliconized analog of clofibrate [silafibrate] in rodents

Silicon is the element very similar to carbon, and bioactive siliconized compounds have therefore received much attention. Siliconization of a compound enhances its biological activities. In the present study the hypolipidemic effect and toxicity of clofibrate and its siliconized analog, silafibrate, were compared. The experiments were performed in hypercholesterolemic Wistar rats. Animals received high fat diet with 62.75% normal chow, 2% cholesterol, 0.25% cholic acid, 15% lard oil, 10% wheat flour and 10% sucrose. Silafibrate[40 mg/kg/day] produced a predominant reduction in the serum levels of total cholesterol [28.4%, p < 0.001], triglycerides [62%, p < 0.0001] and low-density lipoproteins [27%, p < 0.001] being more effective than the reference drug clofibrate [20%, 40%, 14.5%; p < 0.05]. Similarly, it increased the total antioxidant levels in serum by 40% [p < 0.05]. Simultaneously, treatment with silafibrate also reduced the malondialdehyde [MDA] concentration by 41% [p < 0.05]. LD[50] of silafibrate, given orally, was greater than 2000 mg/kg body weight in albino mice while LD[50] for clofibrate was calculated to be 1220 mg/kg. Thirty-day subacute toxicity was also evaluated with oral daily dose at 25, 50 and 100 mg/kg body weight in Wistar rats. No significant changes in body weight, food intake, behavior, mortality, hematology, blood biochemistry, vital organ weight were detected. The results of this study indicate that the effectiveness and safety of the hypolipidemic drug, clofibrate, were enhanced remarkably by replacing chlorine atom in its phenoxy ring with trimethylsilyl

Lovastatin protects mithochondrial and renal function in kidney ischemia-reperfusion in rats / Lovastatina protege a função renal e mitocondrial na isquemia/reperfusão renal em ratos

PURPOSE: To investigate the effect of lovastatin on renal ischemia followed by reperfusion. METHODS: Thirty one Wistar rats submitted to left renal ischemia for 60 minutes followed by contralateral nephrectomy were divided into two groups: A (n =17, control, no treatment), and B (n=14, lovastatin 15 mg/kg/day p.o. ten days before ischemia). The animals were sacrificed at the end of ischemia, after 24 hours and at seven days after reperfusion. Survival, serum urea and creatinine levels and renal mitochondrial function were evaluated. RESULTS: Mortality was 29.4% in group A and 0.7% in group B. Urea and creatinine levels were increased in both groups, but the values were significantly lower in group B. Mitochondrial function showed decoupling in 83.4% of group A, as opposed to 38.4/% of group B. CONCLUSIONS: The result shows a protective action of renal function by lovastatin administered before ischemia/reperfusion. Since most of the mitochondrial fraction presented membranes with the ability to maintain ATP production in group B, stabilization of the mitochondrial membrane should be considered as part of the protective action of lovastatin on renal function in ischemia/reperfusion.

OBJETIVO: Investigar a ação da lovastatina na isquemia renal seguida de reperfusão. MÉTODOS: Trinta e um ratos Wistar submetidos à isquemia renal esquerda durante 60 minutos, seguida da nefrectomia contralateral, foram distribuídos em dois grupos: A (n=17, controle, sem tratamento) e B (n=14, recebendo 15 mg/Kg/dia de lovastatina via oral), durante os dez dias que antecederam a isquemia. Os animais foram mortos ao final da isquemia, e com 24 horas e sete dias após a reperfusão. Foram avaliadas a sobrevida, os valores séricos de uréia e creatinina e a função mitocondrial renal. RESULTADOS: A mortalidade foi 29,4% no grupo A e 0,7% no grupo B. Os níveis de uréia e creatinina elevaram-se nos dois grupos, mas foram significativamente menores no grupo B. No grupo A a função mitocondrial renal ficou desacoplada em 83,4% dos ensaios, enquanto que no grupo B isto ocorreu em apenas 38,4% dos ensaios. CONCLUSÕES: Os resultados mostram que a administração de lovastatina antes do episódio de isquemia protege a função renal. No grupo B, como a maior parte da fração mitocondrial isolada apresentou função acoplada à produção de ATP, deve-se também considerar a estabilização da membrana mitocondrial como parte da ação protetora da lovastatina na função renal durante isquemia e reperfusão.

Evaluation of antihyperlipidemic activity of ethanolic extract of Cassia auriculata flowers.

Hyperlipidemia is a major risk factor for development of coronary artery disease. Cassia auriculata is traditionally used in India for medicinal purposes. In this study, effect of ethanolic extract of Cassia auriculata flowers (Et-CAF) was investigated in Triton WR1339-induced hyperlipidemic rats. Treatment with the Et-CAF (450 mg/kg b.wt) significantly reduced the total cholesterol (TC), triglycerides (TG) and low-density lipoprotein-cholesterol (LDL) levels and significantly increased the high-density lipoprotein (HDL) level associated with reduction of atherogenic index in hyperlipidemic rats. However, there was no change in the serum lipid profile of normal rats treated with Et-CAF alone. The results suggest that Et-CAF has a beneficial effect in treating hyperlipidemia and may serve as a potential drug for prevention of hyperlipidemic atherosclerosis.

Anti-diabetic activity of an hexane extract of Prosthechea michuacana in streptozotocin-induced diabetic rats / Actividad antidiabética de un extracto de hexane de Prosthechea michuacana en ratas diabéticas inducidas por estreptozotocina

In this study we investigated the antihyperglycaemic, antihyperlipidaemic and antiglycation effects of some extracts of Prosthechea michuacana bulbs in normoglycemic and diabetic rats induced by streptozocin (STZ). Hexane, chloroform and methanol extracts of P. michuacana were screened for hypoglycemic activity, and biochemical parameters as serum triglycerides, total cholesterol, lipid peroxidation, liver glycogen, skeletal muscle glycogen levels, superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase activity in diabetic rats. Additionally we determined Glucose 6 Phosphatase and glucokinase activities in liver, inhibition of insulin and protein glycation. Glucose levels in blood plasma were determined by using GOD-POD method. Administration of chloroform and methanol extracts showed no effect on STZ induced diabetic rats (SD). On the other hand, treatment with hexane extract at 200 and 400 mg/kg doses, resulted in a reversal of diabetes and its complications. Both doses significantly brought down blood glucose concentration (35.75 and 47.78 percent in diabetic rats, 50.64 and 57.10 percent in nondiabetic rats), increased glycogenesis and decreased glyconeogenesis bringing the glucose metabolism toward normalcy. These doses also reversed the hyperlipidemia by reducing cholesterol (41.56 percent, 46.08 percent) and triglycerides (37.5 percent, 46.27 percent) and improved hepatic antioxidant enzyme activities. Its effect was compared with that of glibenclamide and tolbutamide, as reference antidiabetic drugs. The hexane extract decreased the hyperinsulinemia by 24 percent in SD and showed a significant change on AGEs formation in vitro with IC50 values of 48.3 ug/ml comparable to inhibitory effect of aminoguanidine with IC50 values of 27.2 ug/ml. It reduced HbA1C levels by 6.4 percent in chronic STZ-diabetic rats. It is concluded that hexane extract of Prosthechea michuacana bulbs possesses anti-hyperglycemic and antihyperlipemic...

En este estudio se determinaron los efectos antidiabéticos, antihiperlipidemico y glicación (AGEs) de algunos extractos de Prosthechea michuacana (PM) en ratas normoglucémicas y con diabetes inducida por estreptozotocina (STZ). Se probó el efecto de los extractos de hexano, cloroformo, metanol de PM sobre la actividad hipoglucemiante, la carga de glucosa, los parámetros bioquímicos tales como triglicéridos, niveles de colesterol total, peroxidación lipídica, glucógeno del hígado, los niveles de glucógeno muscular, niveles de superoxide dismutase, catalasa, glutation reductasa and glutation peroxidasa en ratas normales y diabéticas. También se determinó la glucosa 6 Phosphatasa y las actividades de GK en el hígado, la inhibición de la insulina y la glicosilación de las proteínas. Los niveles de glucosa sanguínea se determinaron por el método de GOD-POD. La administración de los extractos de cloroformo y metanol no presentaron ningún efecto sobre la SD, en cambio el tratamiento con el extracto de hexano (PM) a dosis de 200 y 400 mg/kg, inhibió la diabetes y sus complicaciones. Ambas dosis redujeron significativamente los niveles de glucosa sanguínea (35.75 y 47.78 por ciento en las ratas diabéticas, 50.64 y 57.10 por ciento en las ratas diabéticas), el aumento de la glucogénesis y la disminución de la gluconeogénesis conduce el metabolismo de la glucosa hacia la normalidad. Estas dosis disminuyeron la hiperlipidemia reduciendo el colesterol (41.56 por ciento, 46.08 por ciento) y los triglicéridos (37.5 por ciento, 46.27 por ciento) así como también mejoran las actividades antioxidantes de las enzimas hepáticas. Su efecto se comparó con la glibenclamida y tolbutamida, fármacos usados como antidiabeticos. El extracto de hexano disminuyo la hiperinsulinemia en un 24 por ciento en SD. PM mostró un cambio significativo in vitro sobre la formación de los AGEs con valores de IC50 de 48.3 mg/ml comparable al efecto inhibidor de la aminoguanidina con valores de IC50 de...

Rosuvastatina, resistência à insulina, adiposidade, inflamação e esteatose hepática em camundongos alimentados com dieta hiperlipídica / Beneficial effects of rosuvastatin on insulin resistance, adiposity, inflammatory markers and non-alcoholic fatty liver disease in mice fed a high-fat diet

O estudo teve como objetivo avaliar os efeitos da rosuvastatina (ST) e darosiglitazona sobre a resistência à insulina (RI), morfologia do fígado e do tecido adiposo em camundongos alimentados com dieta hiperlipídica (HF). O tratamento com rosuvastatina resultou em uma acentuada melhoria na sensibilidade à insulina caracterizada pela melhor depuração da glicose durante o teste de tolerância à insulina e uma redução do índice HOMA-IR em 70% (P = 0,0008). O grupo tratado com rosuvastatina apresentou redução no ganho massa corporal (-8%, P <0,01) e menor depósito de gordura visceral (-60%, P <0,01) em comparação com o grupo HF não tratado. Em comparação com camundongos HF, animais do grupo HF+ST reduziram significativamente a massa hepática e a esteatose hepática (-6%; P <0,05% e -21; P <0,01, respectivamente). O grupo HF+ST, reduziu os níveis de triglicerídeos hepáticos em 58% comparado com o grupo HF (P <0,01). Além disso, a expressão de SREBP-1c (proteína 1c ligadora do elemento regulado por esteróis) foi reduzido em 50% no fígado dos animais HF + ST (P <0,01) em comparação com o grupo HF. Os níveis de resistina foram menores no grupo HF + ST comparado com o grupo HF (44% a menos, P <0,01). Em conclusão, demonstramos que camundongos alimentados com dieta HF tratados com rosuvastatina melhoram a sensibilidade à insulina, com redução da esteatose hepática. Além disso, ST reduziu o ganho de massa corporal, melhorou os níveis circulantes de colesterol e triglicerídeo plasmático, com menor conteúdo de hepático de triglicerídeo, que foi concomitante com menor resistina e aumento da adiponectina...

The study aimed to evaluate the effects of rosuvastatin (ST) and rosiglitazone on insulin resistance (IR) and liver and adipose tissue morphologies in mice fed a high-fat (HF) diet. Our data show that treatment with rosuvastatin resulted in a marked improvement in insulin sensitivity characterised by enhanced glucose clearance during insulin tolerance and a decrease in the HOMA-IR index level by 70% (P=0.0008). The group of mice treated with rosuvastatin exhibited reduced body mass gain (-8%; P<0.01) and visceral fat pad thickness (-60%; P<0.01)compared with the untreated HF group. In comparison with HF mice, HF+ST mice showed a significant reduction in hepatomegaly and liver steatosis (-6%; P<0.05 and -21%; P<0.01, respectively). In HF+ST mice, the hepatictriglyceride levels were reduced by 58% compared with the HF group (P <0.01). In addition, the expression of SREBP-1c (sterol regulatory element-binding protein) was decreased by 50% in the livers of HF+ST mice (P<0.01) compared with the HF mice. The levels of resistin were lower in the HF+ST group compared with the HF group (44% less, P< 0.01). In conclusion, we demonstrated that rosuvastatin-treated mice fed HF has been improving in insulin sensitivity, with decreased steatosis found in HF mice. Furthermore, ST reduced body mass gain, improved the circulating levels of plasma cholesterol and triglycerides and reduced hepatic triglycerides, which was concomitant with lower resistin and increased total adiponectin...

[Evaluation of the effect of lycium barbarum fruit feeding on Serum glucose, lipids, HDL-and LDL-cholesterol in diabetic rats]

Use of medicinal plants for attenuation of hyperglycemia and restoration of lipids to normal level is clinically very important. In this study, the effect of oral administration of Lycium barbarum [LB] fruit on serum glucose and lipids was investigated in diabetic rats. Thirty two female Wistar rats were divided into 4 groups; control, LB-treated control, diabetic, and LB-treated diabetic groups. The treatment groups received oral administration of plant [fruit]-mixed pelleted food [at a weight ratio of 6.25%] for 6 weeks. Serum glucose, triglyceride, total cholesterol, LDL-and HDL-cholesterol levels were determined before the study, and at 3rd and 6th weeks after the study. LB treated diabetic rats showed a significant reduction in glucose level compared to non treated group at 3rd and 6th weeks [P<0.01-0.005]. There were no significant changes regarding to total serum cholesterol and triglyceride levels. Meanwhile, LB administration significantly increased HDL-cholesterol level [P<0.05] and reduced LDL-cholesterol level [P<0.01] in treated diabetic group as compared with untreated diabetic group. Oral administration of LB fruit has a significant hypoglycemic effect and led to appropriate changes only in high density lipoprotein-cholesterol and low density lipoprotein cholesterol