Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, we have demonstrated that chronic consumption of a high-fat, high-refined sugar (HFS) diet results in metabolic syndrome which is marked by obesity, insulin resistance, hyperlipidemia, and hypertension in Fischer rats. Metabolic syndrome in this model is associated with oxidative stress, avid nitric oxide (NO) inactivation by reactive oxygen species (ROS), diminished NO bioavailability, and dysregulation of NO synthase isotypes. Although occurrence of oxidative stress and its impact on NO metabolism are well established, the molecular source(s) of ROS in this model is unknown. In an attempt to explore this issue, we measured protein expressions of the key ROS-producing enzyme, NAD(P)H oxidase, and the main antioxidant enzymes, superoxide dismutase (CuZn SOD and Mn SOD), catalase, glutathione peroxidase (GPX), and heme oxygenase-2 (HO-2), in the kidney and aorta of Fischer rats fed an HFS or low-fat, complex-carbohydrate diet for 7 months. In addition, plasma lipid peroxidation product (malondialdehyde) as well as endothelium-dependent and -independent vasorelaxation (aorta rings) was determined. The results showed a significant upregulation of gp91(phox) subunit of NAD(P)H oxidase and downregulations of SOD isoforms, GPX, and HO-2 in the kidney and aorta of the HFS-fed animals. This was associated with increased plasma malondialdehyde concentration and impaired vasodilatory response to acetylcholine, but not the NO donor, Na nitroprusside. The latter findings confirm the presence of oxidative stress and endothelial dysfunction in the HFS-fed rats. Oxidative stress and endothelial dysfunction in the diet-induced metabolic syndrome are accompanied by upregulation of NAD(P)H oxidase, pointing to increased ROS production capacity, and downregulation of SOD isoforms, GPX, and HO-2, the key enzymes in the antioxidant defense system.
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PMID:Oxidative stress and dysregulation of NAD(P)H oxidase and antioxidant enzymes in diet-induced metabolic syndrome. 1678 66

We investigated the effects of a combined treatment with chromium (Cr) and niacin on the spleen, tongue, and lens tissues in terms of lipid peroxidation (LPO), glutathione (GSH), serum catalase (CAT), lactate dehydrogenase (LDH), serum cholesterol, and total lipid levels in normal and hyperlipemic rats. In this study, female 1-year-old Swiss albino rats were used. The rats were randomly divided into four groups. Group I rats (control) were fed with standard pellet chow. Group II rats were fed a lipogenic diet in which 2% cholesterol, 0.5% cholic acid, and 20% sunflower oil were added and were given 3% alcoholic water for 60 days. Group III rats were fed with the same lipogenic diet and were treated with a dose of 250 microg/kg body weight CrCI3 x 6H2O and 100 mg/kg body weight niacin, for 45 days, by gavage. The rats in group IV were fed with pellet chow and treated with 250 microg/kg body weight CrCI3 x 6H2O and 100 mg/kg body weight niacin, by gavage, for 45 days. After 2 weeks, the animals showed symptoms of hyperlipemia. On the 60th day, tissue and blood samples were taken. We have observed decreased CAT activity and GSH levels, increased LDH activity, cholesterol, total lipid, and LPO levels in hyperlipemic rats. Niacin and Cr administration to hyperlipemic rats increased tissue GSH levels and CAT activity and decreased tissue LPO levels and LDH activity, cholesterol, and total lipid levels compared with hyperlipemic rats. We conclude that the administration of a combination of niacin and chromium has a protective effect against oxidative damage to tongue, lens, and spleen tissues as a result of hyperlipemia.
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PMID:The effect of combined treatment with niacin and chromium (III) chloride on the different tissues of hyperlipemic rats. 1693 39

Cyclosporin A (CsA), a calcineurin inhibitor, has been widely used as an immunosuppressant, and is known to induce hyperlipidemia and dyslipoproteinemia with low levels of high-density lipoprotein (HDL). Since apolipoprotein AI (apo AI) is a major protein component of HDL particles and reduction of apo AI results in low levels of HDL, we hypothesized that CsA inhibits apo AI gene expression contributing to its lipid effects. Therefore, we first measured the serum apo AI protein levels in rats with or without CsA treatment, and found that both serum apo AI protein and liver apo AI mRNA levels were significantly reduced in response to CsA treatment. In stably transfected Hep G2 cells harboring an apo AI-474-CAT reporter gene, we found that intracellular calcium mobilization by A23187 a calcium ionophore stimulated apo AI gene expression and the calcineurin inhibitors, CsA and FK605, selectively inhibited this stimulation. Therefore, we conclude that activation of the calcineurin pathway by intracellular calcium mobilization stimulates apo AI gene expression and calcineurin inhibition by CsA results in reduced apo AI gene expression.
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PMID:Cyclosporin A inhibits apolipoprotein AI gene expression. 1703 51

The aim of the present study was to investigate whether hyperlipidemia can cause acute pancreatitis or alter its severity. Male Wistar rats were fed a 3% cholesterol-enriched diet or a normal diet for 16 weeks. Edematous and necrotizing pancreatitis was induced with 3x75 mug/kg body weight of cholecystokinin s.c. and 2x2 g/kg body weight of L-arginine i.p., respectively, in separate groups of normal and hyperlipidemic rats. The severity of the pancreatitis was assessed. We studied the influence of hyperlipidemia on the formation of oxygen-derived free radicals, endogenous scavengers, nitric oxide synthases (NOS), peroxynitrite (ONOO(-)), heat shock protein 72 (HSP72) and nuclear factor-kappa B (NF-kappaB) activation in the pancreas during acute edematous and necrotizing pancreatitis. Hyperlipidemia did not worsen edematous, but aggravated necrotizing pancreatitis. The cholesterol-enriched diet significantly reduced the catalase and Mn-superoxide dismutase (SOD) and constitutive NOS (cNOS) activities and increased the inducible NOS (iNOS) in the pancreas relative to those in the rats on the normal diet. The pancreatic nitrotyrosine level, as a marker of ONOO(-), and the NF-kappaB DNA-binding activity in the pancreas, were significantly elevated in the cholesterol-fed rats. The pancreatic HSP72 expression during necrotizing pancreatitis was not influenced by the hyperlipidemia. The pancreatic Mn-SOD, Cu, Zn-SOD, glutathione peroxidase, total glutathione and cNOS activities were significantly reduced, while the catalase, iNOS and NF-kappaB DNA-binding activities were significantly increased in the animals with necrotizing pancreatitis on the cholesterol diet as compared with those with pancreatitis and receiving the normal diet. Hyperlipidemia induced with this cholesterol-enriched diet leads to decreases in endogenous scavenger and cNOS activities, results in iNOS and NF-kappaB activation and stimulates ONOO(-) generation in the pancreas, which may be responsible for the aggravation of acute necrotizing pancreatitis.
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PMID:Hyperlipidemia induced by a cholesterol-rich diet aggravates necrotizing pancreatitis in rats. 1762 38

We examined oxidative stress and metabolic characteristics of the spontaneously hypertensive hyperlipidemic rat (SHHR) when it was fed a high-fat diet and sucrose solution (HFDS) after N(G)-nitro-L-arginine methyl ester ingestion to develop a rat model of metabolic syndrome. This study was carried out to assess the effects of pioglitazone on levels of lipid peroxide (LPO), Cu,Zn superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GPx), and non-esterified fatty acids (NEFA) in the plasma and liver tissue in HFDS-SHHR compared with Sprague-Dawley rats (SD). In the HFDS-treated groups, levels of LPO, CAT, GPx, and NEFA were elevated and levels of Cu,Zn-SOD were reduced in the plasma and liver tissue, with a marked accumulation of visceral fat. The changes induced by HFDS feeding were severe in the SHHR model that had essential hypertension and hyperlipidemia, when compared with SD that did not have these essential risk factors. Subcutaneous injection of 10 mg/kg per day of pioglitazone for 2 months significantly restored levels of LPO, CAT, GPx, Cu,Zn-SOD, and NEFA in the HFDS-SHHR group, and visceral fat accumulation was reduced. These results suggest that HFDS-SHHR is a suitable model of metabolic syndrome and that pioglitazone treatment can improve oxidative dysregulation in this rat model.
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PMID:Effects of pioglitazone on increases in visceral fat accumulation and oxidative stress in spontaneously hypertensive hyperlipidemic rats fed a high-fat diet and sucrose solution. 1791 67

The aim of present study--comparative characteristic of captopril and of losartan action on the oxidative metabolism in experimental hyperlipidemia. Experiments carried out on rabbits,which were divided into three groups(ten animal in each group) and orally receiving during 45 days: I control group (cholesterol 500mg/kg + methylthiouracil 100mg/kg, II group-captopril 5 mg/kg + cholesterol 500mg/kg + methylthiouracil 100mg/kg, III group-losartan 8mg/kg + cholesterol-500mg/kg + methylthiouracil 100mg/kg. Activity of superoxide dismutase, catalase, level of malonic dialdehyde, osmotic resistance of erythrocytes and resistanse of LDL to oxidation and concentration of nitric oxide in the blood have been evaluated . The administration of captopril and losartan in experimental hyperlipidemia eqivalently increased activity of SOD and catalase, osmotic resistance of erythrocytes and resistanse of LDL to oxidation, whereas decreased content of malonic dialdehyde compared to the control group . Captopril was more effective than losartan in preserving of nitric oxide. We conclude that captopril and losartan inhibited oxidative stress, which are probably associated with the inhibition of angiotensin 11. Captopril and losartan are safely used in patients during cardio-vascular disease with dyslipidemia.
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PMID:[Comparative characteristic of angiotensin-converting enzyme inhibitor--captopril and the angiotensin II receptor blokers--losartan action on the oxidative metabolism in experimental hyperlipidemia in rabbits]. 1798 66

Arsenic, one of the most harmful metalloids, is ubiquitous in the environment. The present study has been carried out to investigate the protective role of a triterpenoid saponin, arjunolic acid (AA) against arsenic-induced cardiac oxidative damage. In the study, NaAsO2 was chosen as the source of arsenic. The free radical scavenging activity and the effect of AA on the intracellular antioxidant power were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of NaAsO2 at a dose of 10 mg/kg body weight for 2 days caused significant accumulation of arsenic in cardiac tissues of the experimental mice in association with the reduction in cardiac antioxidant enzymes activities, namely superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase. Arsenic intoxication also decreased the cardiac glutathione (GSH) and total thiol contents and increased the levels of oxidized glutathione (GSSG), lipid peroxidation end products and protein carbonyl content. Treatment with AA at a dose of 20 mg/kg body weight for 4 days prior to NaAsO2 intoxication protected the cardiac tissue from arsenic-induced oxidative impairment. In addition to oxidative stress, arsenic administration increased total cholesterol level as well as the reduced high-density lipoprotein cholesterol level in the sera of the experimental mice. AA pretreatment, however, could prevent this hyperlipidemia. Histological studies on the ultrastructural changes in cardiac tissue supported the protective activity of AA also. Combining all, results suggest that AA could protect cardiac tissues against arsenic-induced oxidative stress probably due to its antioxidant property.
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PMID:Arsenic-induced oxidative myocardial injury: protective role of arjunolic acid. 1819 99

Oleuropein-rich extracts from olive leaves and their enzymatic and acid hydrolysates, respectively rich in oleuropein aglycone and hydroxytyrosol, were prepared under optimal conditions. The antioxidant activities of these extracts were examined by a series of models in vitro. In this study the lipid-lowering and the antioxidative activities of oleuropein, oleuropein aglycone and hydroxytyrosol-rich extracts in rats fed a cholesterol-rich diet were tested. Wistar rats fed a standard laboratory diet or cholesterol-rich diets for 16 weeks were used. The serum lipid levels, the thiobarbituric acid reactive substances (TBARS) level, as indicator of lipid peroxidation, and the activities of liver antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) were examined. The cholesterol-rich diet induced hyperlipidemia resulting in the elevation of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C). Administration of polyphenol-rich olive leaf extracts significantly lowered the serum levels of TC, TG and LDL-C and increased the serum level of high-density lipoprotein cholesterol (HDL-C). Furthermore, the content of TBARS in liver, heart, kidneys and aorta decreased significantly after oral administration of polyphenol-rich olive leaf extracts compared with those of rats fed a cholesterol-rich diet. In addition, these extracts increased the serum antioxidant potential and the hepatic CAT and SOD activities. These results suggested that the hypocholesterolemic effect of oleuropein, oleuropein aglycone and hydroxytyrosol-rich extracts might be due to their abilities to lower serum TC, TG and LDL-C levels as well as slowing the lipid peroxidation process and enhancing antioxidant enzyme activity.
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PMID:Hypolipidimic and antioxidant activities of oleuropein and its hydrolysis derivative-rich extracts from Chemlali olive leaves. 1882 63

Hyperlipidemia/hypercholesteremia are major risk factors for atherosclerosis and cardiovascular diseases. Root of Asparagus racemosus (AR) is widely used in Ayurvedic system of medicine in India and is known for its steroidal saponin content. This study was designed to investigate the hypocholesteremic and antioxidant potential of AR root in both normo- and hypercholesteremic animals. Normal and hypercholesteremic male albino rats were administered with root powder of AR (5 and 10 g% dose levels) along with normal and hypercholesteremic diets, respectively, for a duration of 4 weeks. Plasma and hepatic lipid profiles, fecal sterol, bile acid excretion and hepatic antioxidant activity were assessed. Inclusion of AR root powder in diet, resulted in a dose-dependant reduction in plasma and hepatic lipid profiles, increased fecal excretion of cholesterol, neutral sterol and bile acid along with increases in hepatic HMG-CoA reductase activity and bile acid content in hypercholesteremic rats. Further, AR root also improved the hepatic antioxidant status (catalase, SOD and ascorbic acid levels). No significant changes in lipid and antioxidant profiles occurred in the normocholesteremic rats administered with AR root powder. AR root appeared to be useful as a dietary supplement that offers a protection against hyperlipidemia/hypercholesteremia in hypercholesteremic animals. The results of the present study indicate that the potent therapeutic phyto-components present in AR root i.e. phytosterols, saponins, polyphenols, flavonoids and ascorbic acid, could be responsible for increased bile acid production, elimination of excess cholesterol and elevation of hepatic antioxidant status in hypercholesteremic conditions.
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PMID:Asparagus root regulates cholesterol metabolism and improves antioxidant status in hypercholesteremic rats. 1895 32

We investigated the influence of the flavonoid-rich fraction from Spermacoce hispida seed (S-Frf) on PPAR-alpha gene expression, plasma and erythrocyte antioxidants status, protein metabolism, and marker enzymes in diabetic hyperlipidemic rats. Hyperlipidemia was induced by feeding a 20% high fat diet (HFD) to male albino Wistar rats for 66 days. Diabetes was induced on the 17th day by a single i.p. injection of streptozotocin (50 mg/kg). When compared with diabetic hyperlipid-emic rats, plasma TBARS and LOOH levels decreased, the activities of enzymic antioxidants (SOD, CAT, GPx) and plasma GSH levels increased in the S-Frf fed group. The activities of plasma hepatic markers serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, and levels of plasma urea, uric acid, creatinine, globulin, A/G ratio significantly decreased, whereas liver weight, total protein, and albumin increased. Oral administration of S-Frf up-regulates PPAR-alpha (peroxisome proliferator activated receptor alpha) gene expression, activates fatty acid catabolism, and is involved in the control of lipoprotein assembly in liver. The results show that S-Frf has an antihyperlipidemic effect, improves antioxidant status, and alleviates liver and kidney damage associated with HFD-fed-STZ rats by up-regulating PPAR-alpha mRNA.
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PMID:Influence of flavonoid-rich fraction from Spermacoce hispida seed on PPAR-alpha gene expression, antioxidant redox status, protein metabolism and marker enzymes in high-fat-diet fed STZ diabetic rats. 1966 17


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