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

Efecto de la combinación de dieta hiperlipídica y la privación de estrógeno sobre la integridad ósea bucal de ratas / Effect of association high fat diet: hypoestrogenism on bone integrity: of oral rats

El objetivo de este estudio fue evaluar el efecto de la deficiencia de estrógenos asociada con dieta hiperlipídica sobre la integridad de la mandíbula de ratas. Para este experimento se selecionaron Ratas Wistar fueron divididas en 4 grupos: Control (C4%), Control hiperlipídica19% (C19%), ovariectomizadas 4% (OVX4%) y Ovariectomizada 19% (OVX19%). El experimento empezó con la castración (90 días), seguida de dieta hiperlipídica durante 30 días. Al fin, la sangre fue recogida para el análisis de los niveles séricos de calcio, fósforo, fosfatasa alcalina y estradiol. El fósforo disminuyó cuando hay aumento de la fosfatasa alcalina en todos los grupos en comparación con el C4%. En las vértebras L4, los pesos inmersos y húmedos aumentarán con la castración y la dieta hiperlipídica, mientras que el porcentaje de materia orgánica y minerales disminuyeron. En las mandíbulas, los pesos inmersos, húmedos y la densidad ósea aumentaran con la castración, pero disminuyeron con la combinación de castración / dieta. En las cenizas de las mandíbulas, el porcentaje de magnesio aumentó significativamente en todos los grupos. En las pruebas biomecánicas de las vértebras L4 y fémur no se encontraron diferencias significativas entre los grupos. Sin embargo, los grupos alimentados con dieta hiperlipídica tuvieron una menor resistencia a la tensión aplicada en la mandíbula. Dentro de las limitaciones del estudio, se puede notar que en estas ratas, la deficiencia de esteroides sexuales asociada con la dieta hiperlipídica influye negativamente sobre la integridad del hueso mandibular...

The aim of this study was to evaluate the effect of estrogen deficiency associated with a high fat diet on bone integrity of the jaw of rats. The pregnant rats were evaluated by vaginal cytology were 90 days old, divided into four groups: Control (C4%), Control hiperlipídica19% (C19%), ovariectomized 4% (OVX4%) and Ovariectomized19% (OVX19%). The experiment began with castration (90 days), followed by feeding with a high fat diet for 30 days. At the end, blood was collected. Jaws, vertebrae L4 and femur were removed and prepared for analysis. There were no differences in food intake, the body length or in bone measurements. Serum calcium decreased in the castrated groups. The level of phosphorus decreased and alkaline phosphatase increased in all groups. Some differences were observed among physical parameters. L4 vertebrae, immersed and wet weights increased with castration and the high fat diet, while the percentage of organic material and mineral decreased. In the jaws, immersed and wet weights and bone density increased with castration, but decreased with the combination spaying/fat diet. Bone volume and percentage of water decreased with intake of high fat diet. In the ashes of the jaws percentages of magnesium were increased in all groups, without changes in calcium and phosphorus. Groups fed with high-fat diets had lower resistance to the applied voltage in the jaw. It was demonstrated in these rats that, the deficiency of sex steroids associated with a high fat diet negatively influences mandibular bone integrity...

Daño oxidativo en un modelo experimental de hiperglicemia e hiperlipidemia inducida por sacarosa en ratas wistar / Oxidative damage in an experimental model of saccharose-induced hyperglycemia and hyperlipidemia in Wistar rats

Se realizó un estudio experimental de casos y controles en el período comprendido entre noviembre de 2010 y mayo de 2011, con el objetivo de caracterizar el comportamiento del daño oxidativo en un modelo experimental de hiperglicemia e hiperlipidemia inducida por sacarosa en ratas wistar en la Unidad de Toxicología Experimental de la Universidad de Ciencias Médicas de Villa Clara. Para ello se utilizaron ratas machos como modelo biológico, con el fin de evaluar la actividad oxidativa inducida por sacarosa. El modelo fue establecido a partir de la administración de una dieta rica en sacarosa, para lo cual se determinaron los por cientos de hemólisis, fotohemólisis y la susceptibilidad a sustancias con efectos hemolíticos. Se encontró aumento en los valores de glucemia y triacilglicéridos de las ratas del grupo estudio, con diferencias significativas con respecto al grupo control. Asimismo, se obtuvieron diferencias significativas entre ambos grupos estudiados en los test de susceptibilidad a la hemólisis y la fotohemólisis. Se produjo incremento significativo en los niveles de glicemia y triacilglicéridos relacionados con la dieta rica en sacarosa. Se observaron incrementos significativos en los valores de los por cientos de hemólisis en el ensayo de susceptibilidad a la hemólisis y la fotohemólisis y en el primer caso se correspondió con el grupo sometido a la dieta rica en sacarosa. Se observó una fuerte correlación entre los niveles de triglicéridos del grupo estudio en el último mes de experimentación y los valores obtenidos en el test de fotohemólisis.

We carried out an experimental research of cases and controls in the period from November 2010 to May 2011, with the objective of characterizing the behavior of the oxidative damage in an experimental model of saccharose-induced hyperglycemia and hyperlipidemia in Wistar rats in the Unit of Experimental Toxicology of the Medical Sciences University of Villa Clara. We used male rats as biological model, with the objective of evaluating the saccharose- induced oxidative activity. The model was set up on the basis of a diet rich in saccharose, and for that there were calculated the hemolysis, photohemolysis percentages and the susceptibility to substances with hemolytic effects. We found an increase in the glycemia and triacilglyceride values of the rats in the studied group, with significant differences in those of the control group. There were also found significant differences between the both studied groups in the tests of susceptibility to the hemolysis and photohemolysis. There it was a significant increase in the glycemia and triacilglycerides levels related with the saccharose-enriched diet. We observed significant increases in the percentages values of the hemolysis in the tests of susceptibility to the hemolysis and photohemolysis, and in the first case it corresponded with the group receiving a saccharose- enriched diet. There it was a strong correlation between the triglycerides level of the studied group in the last month of the research and the values obtained in the photohemolysis test.

Lindane-induced biochemical perturbations in rat serum and attenuation by omega-3 and Nigella sativa seed oil.

Lindane (-hexachlorocyclohexane, -HCH), a highly persistent organochlorine insecticide is neurotoxic at acute doses and has been reported to induce oxidative stress in cells and tissues. In this study, we investigated the antioxidant property of Nigella sativa seed oil (N.O) and omega-3 polyunsaturated fatty acids (3) against -HCH-induced oxidative hepatic and renal damage in male rats serum. Rats were orally given sublethal dose of -HCH (12 mg/kg, 24 h prior to decapitation), while N.O (0.3 ml/kg) and 3 (20 mg/kg) were given every 48 h for 20 days single or together, or also combined with -HCH. -HCH caused a significant increase in the levels of serum total lipids, cholesterol, and triglycerides by 49, 61 and 30% respectively, while HDL-cholesterol decreased by 45% compared to control group. Pretreatment with 3 and N.O prior -HCH administration re-established the altered biochemical features and alleviated the harmful effects of g-HCH on lipid profile. The concentration of serum total protein and albumin was significantly decreased by 35 and 45% respectively in rats treated with -HCH compared to control. -HCH also caused hepatic and renal damage, as observed from the elevated serum levels of urea, creatinine, total bilirubin and uric acid contents and aminotransferases (AST and ALT), phosphatases (ACP and ALP) and lactate dehydrogenase (LDH) activities. Co-administration of 3 and N.O reversed the hazardous effects induced by -HCH on the liver and kidney and also protected acetylcholinesterase from the inhibitory action of -HCH as well as suppressed the lipid peroxidation. Thus, the results show that 3 and N.O might prevent oxidative stress and attenuate the changes in the biochemical parameters induced by -HCH in male rats.

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.

Modelo experimental de hiperlipidemia con el empleo de caseína y grasas saturadas / Experimental model of hyperlipidaemia with the use of casein and saturated fats

En el presente trabajo se evaluó el efecto hiperlipídico de una dieta combinada de caseína y grasas saturadas, en un modelo biológico conformado por ratas Wistar. Se integraron tres grupos experimentales de seis animales cada uno: el primero (grupo control) consumió una dieta convencional; el segundo, una dieta convencional combinada con caseína y grasa de cerdo al 20 por ciento y el tercero, la dieta convencional suplementada solamente con grasa de cerdo al por ciento. Fueron cuantificados el colesterol y los triacilglicéridos por métodos enzimáticos en tres momentos diferentes: al comienzo del estudio, a los 15 días y al finalizar este. El incremento de peso corporal, una vez finalizada la investigación, no mostró diferencias significativas entre los grupos de experimentación. El grupo de la dieta combinada elevó el perfil lipídico más eficientemente que el que solo consumió grasas saturadas, lo cual confirma que el modelo experimental de hiperlipidemia inducida por dieta suplementada con caseína y grasas saturadas es el más eficaz para la elevación del perfil lipídico

In the current research it was evaluated the hyperlipidic effect of a combined diet with casein andsaturated fats, in a biological model conformed by Wistar's rats. Three experimental groups wereintegrated with six animals in each one. The first group (control group) consumed a conventionaldiet; the second group, a conventional diet combined with casein and pig fat at 20 %; and the thirdone, the same conventional diet supplemented just with pig fat at 20 %.The cholesterol andtriacylglycerols were quantified by means of enzymatic methods in three different moments: at thebeginning of the study, after 15 days and at the end of this. The increase of body weight, once itwas finished the research, didn't show significant differences among the experimental groups. Thegroup of the combined diet increased its lipidic profile more efficiently than the group that justconsumed saturated fats, which confirms that the experimental model of induced hyperlipidaemiaby supplemented diet with casein and saturated fats is the most effective for the elevation of lipidicprofile.

Hypolipidemic activity of Hibiscus rosa sinensis root in rats.

The hypolipidemic activity of Hibiscus rosa sinensis (family Malvaceae) root extract was studied on triton and cholesterol-rich high fat diet (HFD) induced models of hyperlipidemia in rats. In triton WR-1339-induced hyperlipidemia, feeding with root extract (500 mg/kg body wt/day p.o.) exerted lipid-lowering effect, as assessed by reversal of plasma levels of total cholesterol (TC), phospholipids (PL) and triglycerides (TG) and reactivation of post-heparin lipolytic activity (PHLA) of plasma. The other model was fed with cholesterol-rich HFD and root extract (500 mg/kg body wt/ day p.o.) simultaneously for 30 days. This also caused lowering of lipid levels in plasma and liver homogenate and reactivation of plasma PHLA and hepatic total lipoprotein lipase activity. The hypolipidemic activity of Hibiscus rosa sinensis root was compared with a standard drug guggulipid (200 mg/kg body wt/day p.o.), a known lipid- lowering agent in both models. Histopathological findings in rat liver supported the protective role of H. rosa sinensis root extract in preventing cholesterol-rich HFD-induced hepatic steatosis.

Effect of exogenous selenium on nicotine induced hyperlipidemia in rats.

The effect of two different doses (1 microg Se/Kg and 50 microg Se/Kg Body wt) of selenium on nicotine induced hyperlipidemia was investigated in rats. Results revealed that nicotine intake caused an increase in concentration of cholesterol, triglycerides, free fatty acids, phospholipids and low density lipoprotein compared to control group. Coadministration of selenium along with nicotine reduced the levels of lipids compared to nicotine group. This reduction was due to reduction in the biosynthesis of lipids as evidenced by the reduced activity of HMGCoA reductase and lipogenic enzymes. Nicotine intake also reduced the absorption of selenium in the intestine. Histopathological studies revealed that selenium at a dose of 1 microg was more effective in reducing lipid levels and higher dose of selenium was toxic.

Antiretroviral treatment for HIV infection/AIDS and the risk of developing hyperglycemia and hyperlipidemia

A cross-sectional study with internal comparison groups was conducted to describe sociodemographic characteristics, as well as verify the association between the type of antiretroviral treatment used and hyperglycemia and hyperlipidemia, with special attention to the use of HIV protease inhibitors. The data was obtained through an interview questionnaire, as well as blood and urine samples that were collected for the laboratory exams. A total of 418 patients were interviewed. 46 of these, however, met the exclusion criteria. The sample was therefore composed by 372 HIV positive patients, attended at the laboratory of the Correia Picanço State Hospital for the collection of blood, to estimate the HIV viral load and/or TCD4 cell counts from August to November 2000. The association between the variables was tested using the chi-square test and the p-value. A multiple logistic regression analysis was carried out to adjust for potential confounding factors. A greater frequency of patients with high glucose levels was observed among those making use of antiretroviral therapy without protease inhibitors, but the number of patients limited the comparisons. An association was verified between the total serum cholesterol level and the use of HIV protease inhibitors (p = 0.047) even after controlling for age. An association was also observed between the triglyceride levels and the use of HIV protease inhibitors, which remained after adjustment for age, sex and creatinine levels (p < 0.001). The levels of glucose and TSH, the presence of proteinuria and the practice of physical activity were not associated either with the levels of cholesterol or with the levels of tryglicerides thus they were not confounders of the associations described.

Um estudo epidemiológico transversal, com caráter analítico, foi realizado para descrever características sócio-demográficas bem como verificar a associação entre o tipo de tratamento antiretroviral empregado e hiperglicemia e hiperlipidemia, com especial atenção aos pacientes em uso de inibidores da protease do HIV. As informações foram obtidas a partir de um questionário e da coleta de sangue e urina para a execução dos exames laboratoriais. Foram entrevistados 418 pacientes, sendo que 46 indivíduos foram excluídos do estudo. A amostra foi então composta por 372 pacientes soropositivos para o HIV atendidos no ambulatório do Hospital Correia Picanço da Secretaria Estadual de Saúde, no período de agosto a novembro de 2000. O teste do Qui-quadrado foi usado para testar as associações e a regressão logística múltipla para ajustar pelos potenciais fatores de confusão. Observou-se uma maior frequência de pacientes com níveis elevados de glicose entre aqueles que faziam uso de terapia antiretroviral sem inibidores da protease, mas o pequeno número de indivíduos limitou as comparações. Verificou-se uma associação entre o colesterol total e o uso de inibidores da protease (p = 0,047) mesmo após o ajuste por idade. Verificou-se também uma associação entre os níveis de triglicerídeos e o uso de inibidores da protease que permaneceu estatisticamente significante mesmo após o ajuste por idade, sexo e níveis de creatinina (p < 0,001). Os níveis de glicose, de TSH, a presença de proteinúria e a pratica de exercícios físicos não estiveram associados com os níveis de colesterol ou com os níveis de triglicerídeos, não se caracterizando como fatores de confusão das associações descritas.

Hypolipidemic and antihyperlipidemic effects of Lagenaria siceraria (Mol.) fruit extracts.

Bottle gourd [(Lagenaria siceraria (Mol.) Stand.] fruit is ascribed with many therapeutic effects. The present study was undertaken to explore the antihyperlipidemic effect of four different extracts viz. petroleum ether, chloroform, alcoholic and aqueous extracts from bottle gourd in Triton-induced hyperlipidemic rats and their hypolipidemic effects in normocholesteremic rats. The study is comprised preliminary phytochemical screening of the extracts. Oral administration of the extracts, at doses of 200 and 400 mg/kg body weight in rats, dose-dependently inhibited the total cholesterol, triglycerides, low-density lipoproteins level, and significantly increased the high density lipoproteins level. However, petroleum ether extract did not show the significant effects. Both the chloroform and alcoholic extract exhibited more significant effects in lowering total cholesterol, triglycerides and low density lipoproteins along with increase in HDL as compared to the others. Preliminary phytochemical screening revealed the presence of flavonoids, sterols, cucurbitacin saponins, polyphenolics, proteins, and carbohydrates. The results obtained suggest marked antihyperlipidemic and hypolipidemic activity of the extracts.

Hyperlipidemia and glucose intolerance in patients with HIV infection receiving antiretroviral therapy

OBJETIVO: Determinar la prevalencia de los efectos secundarios sobre el metabolismo de los lípidos y la glucosa provocados por la terapia antirretrovírica hiperactiva (TARHA), así como el impacto que el uso de los distintos esquemas de antirretrovíricos tiene sobre los lípidos y la glucosa en un grupo de pacientes de Yucatán, México.MATERIAL Y MÉTODOS: Se realizó un estudio transversal. A cada paciente se le aplicó un cuestionario creado para este estudio y se le determinaron los valores de colesterol total, triglicéridos y glucosa en ayuno. Se determinó la prevalencia de hiperlipidemia y alteraciones de la glucosa y su relación con las variables de la encuesta.RESULTADOS: Se estudiaron 211 pacientes, 36 (17%) mujeres y 175 (83%) hombres; 92 (44%) tuvieron hiperlipidemia. De éstos, 43 (20%) presentaron hipercolesterolemia (HC) y 82 (39%) hipertrigliceridemia (HT). La presencia de HC e HT combinadas se verificó en 30 (14%) pacientes; además, 19 (9%) pacientes exhibieron alteraciones en la glucosa, seis (3%) presentaron diabetes mellitus y 13 (6%), intolerancia a la glucosa. Las variables que se vincularon con la presencia de hiperlipidemia fueron los números de linfocitos CD4 >350 células/µl [RM= 2.79 (1.08-7.27), p= 0.03], el género masculino [RM= 3.6 (1.4-9.12), p= 0.006] y el uso de nucleósidos inhibidores de la transcriptasa inversa (NITI) [RM= 3.1 (1.2-8.1), p= 0.01].CONCLUSIONES: Los pacientes con la infección por el VIH que reciben terapia antirretroviral (TAR) tienen un riesgo aumentado de presentar dislipidemia. A diferencia de lo que informan la mayor parte las publicaciones, las alteraciones de los lípidos se asociaron con más frecuencia al uso de NITI, por lo que se concluye que la patogenia de estas alteraciones no es única y que resulta probable la existencia de un efecto sinérgico entre las distintas familias de fármacos antirretrovíricos y que otros factores del huésped participen en la génesis de estas alteraciones.

Antipsicóticos atípicos y trastornos metabólicos / Atypical antipsychotics and metabolic disorders

Over the last decade, a revolution in the management of psychosis was set with the introductions of atypical antipsychotics, especially with their action on both positive and negative schizophrenia symptoms. In the other hand, their better tolerance and reduction of extrapyramidal symptoms meant a better adherence to treatment and quality of life. Although, schizophrenic and bipolar patients have shown to have higher rates of diabetes and hiperlipidemia, , as well a tendency to overweight and obesity, reports of metabolic effects have become more common whit the use on novel anti psychotics. The authors analyze the existing data of articles they chose to be representative of the prevalence, causes, evolution, treatment and prevention of obesity, type II diabetes and hiperlipidemia secondary to atypical antypsychotics; they also contribute with a critical attitude towards this issue.

Con la introducción de los antipsicóticos atípicos en la década anterior se produjo una revolución en el manejo de los desórdenes psicóticos al tener dichos fármacos acción sobre los síntomas positivos y negativos de la esquizofrenia. Por otra parte, la mejor tolerancia y la reducción de los síntomas extrapiramidales significaron una mejor adherencia al tratamiento y una mejora en la calidad de vida. Si bien, tanto los pacientes esquizofrénicos como bipolares, tienen de por sí un incremento en las tasas de diabetes e hiperlipidemia, así como una tendencia al sobrepeso y la obesidad; cada vez se han hecho más frecuentes los reportes de efectos metabólicos con el uso de antipsicóticos atípicos. Los autores realizan una revisión de los artículos que a juicio de ellos, resumen la prevalencia, causa, evolución, tratamiento y prevención de la obesidad, diabetes mellitus II e hiperlipidemia secundaria a los antipsicóticos atípicos; del mismo modo, aportan una actitud crítica respecto al tema.

Effect of ascorbic acid, alpha-tocopherol, lecithin and L-ornithine-L-aspartate on ethanol induced hypoproteinemia and hyperlipidemia in rats.

We studied effect of exogenous ascorbic acid, alpha-tocopherol, lecithin and L-ornithine-L-aspartate on serum lipids and proteins in experimental hepatotoxic Wistar rats. Eleven groups (n = 6) of animals were used. Hepatotoxicity was induced by administering ethanol (1.6 g/kg/day) for 28 days. Both preventive and curative options were studied. Percentage increase in body weight was significantly lower in ethanol treated rats. Ethanol significantly (P<0.05) increased cholesterol, triglycerides and LDL, and decreased protein, albumin and A:G ratio in serum. Ascorbic acid, alpha-tocopherol, lecithin and L-ornithine-L-aspartate exhibited an ability to counteract the alcohol-induced changes in the body weight and biochemical parameters in preventive and therapeutic models in varying degree. Antioxidants showed better effect.

Biochemical effects of garlic protein on lipid metabolism in alcohol fed rats.

Garlic protein is a very good hypolipidemic agent. In the present study the water soluble protein fraction of garlic was investigated for its effect on hyperlipidemia induced by alcohol (3.76 g/kg. body wt./day). The hypolipidemic action is mainly due to an increase in cholesterol degradation to bile acids and neutral sterols and mobilization of triacyl glycerols in treated rats. Garlic protein (500 mg./kg body wt./day) showed significant hypolipidemic action comparable with a standard dose of gugu-lipid (50 mg./kg. body wt./day).

Effect of atenolol and labetalol on serum lipids.

Adverse alterations in lipid profile suggesting higher atherogenicity were observed following 12 weeks treatment with atenolol in patients of hypertension. No significant alterations in lipid profile were observed with labetalol therapy.

The hypolipidemic effect of onion (Allium cepa Linn) in sucrose fed rabbits.

Long term administration of sucrose significantly increased triglyceride levels in normal rabbits. Effects of an aqueous extract of onion on the sucrose fed rabbits have been investigated. Administration of onion extract significantly reduced serum, liver and aorta triglycerides and serum and liver proteins. On the other hand liver free amino acids have been significantly increased in the onion treated group as compared to the sucrose fed control. The effects of onion have been ascribed to its sulfur containing principles which oxidize thiol compounds either present free or combined in a protein and NADPH which are necessary for lipid synthesis.