Animals ; Arsenates ; toxicity ; Female ; Kidney ; drug effects ; Lipid Metabolism ; drug effects ; Liver ; drug effects ; Oxidative Stress ; drug effects ; Rats, Wistar

Lipid metabolism disorder is an important risk factor to obesity, hyperlipidemia and type 2 diabetes as well as other chronic metabolic disease. It is also a key target in preventing metabolic syndrome, chronic disease prevention. Plant polyphenol plays an important role in maintaining or improving lipid profile in a variety of ways. including regulating cholesterol absorption, inhibiting synthesis and secretion of triglyceride, and lowering plasma low density lipoprotein oxidation, etc. The purpose of this article is to review the lipid regulation effects of plant polyphenols and its related mechanisms.
Animals ; Humans ; Lipid Metabolism ; drug effects ; Metabolic Diseases ; drug therapy ; metabolism ; Polyphenols ; pharmacology

OBJECTIVETo explore the effect of Danshensu on the lipid metabolism of hyperlipidemic rats.

METHODSixty clean male SD rats were selected. Twelve of them were selected in the basic control group and fed with common foods, and the remaining rats were fed with the high-fat feeds. After the successful modeling, they were randomly divided into the high-fat control group and low dose (10 mg x kg(-1) x d(-1)), medium dose (20 mg x kg(-1) x d(-1)) and high dose (40 mg x kg(-1) x d(-1)) Danshensu (dissolved in saline) groups. Both of the two groups were abdominally injected with the same volume of normal saline once a day for consecutively 30 days. The serum TG, TC, HDL-C and liver ACC1, FAS, HMGR, CPT-I mRNA expressions were detected.

RESULT AND CONCLUSIONDanshensu could inhibit the LDL-C level, timely clear redundant cholesterol and effectively regulate the lipid metablism of hyperlipidemic rats by reducing the TC content, decrease the fatty acid by reducing the FAS mRNA expression, and reduce the synthesis levels of endogenous cholesterol by inhibit the HMGR mRNA expression.

Animals ; Hyperlipidemias ; drug therapy ; metabolism ; Lactates ; pharmacology ; Lipid Metabolism ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of carbon disulfide (CS(2)) on oxidation-antioxidation function of rat nerve tissues.

METHODSThirty male Wistar rats were randomly divided into the control group, the low-dosage exposure group and the high-dosage group, 10 rats each. The rats of the two exposure groups were administered with CS(2) by gavage at a dosage of 300 or 500 mgxkg(-1)xd(-1), 5 times every week for continuous 12 weeks. The alterations in glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), hydrogen peroxidase (CAT) and total anti-oxidation (T-AOC) in cerebrum, spinal cord, and sciatic nerve of CS(2)-treated animals were assayed.

RESULTSThe results showed that the contents of MDA and ROS in nerve tissues of CS(2)-treated groups increased significantly except ROS in spinal cord and sciatic nerve of low dose group. The content of MDA was increased by 20.7% and 33.6% respectively in the cerebrum of the rats of the low-dosage group and the high-dosage group, by 18.5% and 23.3% respectively in the spinal cord, and by 20.7% and 53.0% respectively in the sciatic nerve, The content of MOS was increased by 20.1% and 34.9% respectively in the cerebrum of the rats of the low-dosage group and the high-dosage group, and by 14.1% and 15.4% respectively in the spinal cord and the sciatic nerve of the rats of the high-dosage group (P < 0.05 or P < 0.01). Furthermore, the activities of SOD, GSH-Px, CAT and T-AOC decreased significantly except GSH-Px and SOD in cerebrum of low dose group. The content of GSH was decreased by 17.2% and 26.5% respectively in the cerebrum of the rats of the low-dosage group and the high-dosage group, by 26.4% and 31.2% respectively in the spinal cord, and by 15.1% and 20.0% respectively in the sciatic nerve. The content of T-AOC was decreased by 11.1 and 26.4% respectively in the cerebrum of the rats of the low-dosage group and the high-dosage group, by 15.1% and 38.4% respectively in the spinal cord, and by 35.6% and 42.3% respectively in the sciatic nerve. The activity of SOD was decreased by 12.1% and 25.4% respectively in the spinal cord of the rats of the low-dosage group and the high-dosage group and by 16.4% and 30.3% respectively in the sciatic nerve. The activity of GSH-Px was decreased by 17.3% and 32.5% respectively in the spinal cord of the rats of the low-dosage group and the high-dosage group and by 17.1% and 21.5% respectively in the sciatic nerve. The activity of GSH-Px and SOD was decreased by 12.6% and 30.1% respectively in the cerebrum of the rats of the high-dosage group. The activity of CAT was decreased by 17.5% and 39.4% respectively in the cerebrum of the rats of the low-dosage group and the high-dosage group, by 25.2% and 31.3% respectively in the spinal cord, and by 17.1% and 36.9% respectively in the sciatic nerve (P < 0.05 or P < 0.01).

CONCLUSIONSubchronic exposure to CS(2) can induce significant changes of oxidation-antioxidation function in rat nerve tissues, which might be related to CS(2)-induced neurotoxicity.

Animals ; Antioxidants ; metabolism ; Carbon Disulfide ; Lipid Peroxidation ; drug effects ; Nerve Tissue ; metabolism ; Rats ; Rats, Wistar

Animals ; Biogenic Monoamines ; metabolism ; Brain ; drug effects ; metabolism ; Female ; Lipid Peroxidation ; drug effects ; Male ; Mice ; Paraquat ; toxicity

OBJECTIVETo observe the effects of panax quinquefolius saponin (PQS) of stem and leaf on glucose-lipid metabolism and insulin signal transduction in the insulin resistant model of adipocytes.

METHODSThe insulin resistant model of differentiated 3T3-L1 adipocytes was established in vitro with free fatty acid. After induction of insulin resistance, cells were treated with metformin or PQS for 2 days. The glucose consumption in culture fluid was detected by glucose oxidase method; the effects of PQS on the lipolysis induced by tumor necrosis factor (TNF-alpha) was observed using colorimetry; and the phospholation of signal proteins was detected by Western-blot.

RESULTSThe amount of glucose consumption (mmol/L) in the model group (5.250 +/- 2. 671) was significantly lower than that in the normal control group (14.133 +/- 1.305, P < 0.01), it increased in the meformin treated group (11.807 +/- 1.358), and the groups treated with high-, middle- and low-dose PQS dose-dependently (10.784 +/- 2.373, 10.217 +/- 1.237 and 9.984 +/- 2.006, respectively), significantly higher than that in the model group (P < 0.01). Upon TNF-alpha treatment, the concentration of free fatty acid (FFA) (nmol/ microg) in culture medium was 2.479 +/- 0.597, predominantly higher than that in the control group (1.320 +/- 0.538, P < 0.01), while it was 1.210 +/- 0.566 in the metformin group, 1.105 +/- 0.631 in high-dose PQS group, 1.108 +/- 0.260 in the middle-dose PQS group, 1.201 +/- 0.593 in the low-dose PQS group, all were lower than that in the TNF-alpha group (P < 0.05 or P < 0.01), and a dose-dependent tendency of PQS's action was seen. The tyrosine phosphorylation of insulin receptor and IRS-1 as well as Ser473 phosphorylation of PKB were lower in the model group than in the control group; they were insignificantly changed in the low-dose PQS group, but did show significant difference in comparing with those in the high-and middle-dose PQS groups or metformin group.

CONCLUSIONPQS can accelerate the glucose utilization and depress the lipolysis in adipocytes induced by TNF-alpha, which may be correlated with its promoting insulin signal transduction and improving insulin resistance in adipocytes.

3T3-L1 Cells ; Adipocytes ; drug effects ; metabolism ; Animals ; Glucose ; metabolism ; Insulin ; metabolism ; Insulin Resistance ; Lipid Metabolism ; drug effects ; Mice ; Saponins ; pharmacology ; Signal Transduction ; drug effects

Oxidized low density lipoprotein (oxLDL) can trigger intracellular production of reactive oxygen species and lipid peroxidation (LPO), and is thought to contribute to initiation and progression of atherosclerosis. In order to understand the correlation between oxLDL and macromolecular damage, we measured levels of LPO-derived miscoding etheno-DNA adducts and LPO-modified proteins in cultured human vascular endothelial and smooth muscle cells after incubation with oxLDL for up to 48 h. A semi-quantative analysis method for 1, N6-ethenodeoxyadenosine (ɛdA) by immunohistochemistry was applied. After oxLDL stimulation, ɛdA-stained nuclei were significantly increased in both endothelial and smooth muscle cells. Similarly, 4-hydroxy-2-nonenal (4-HNE)-modified proteins, as analyzed by immunohistochemistry and Western blotting, were also 3-5 fold increased. It was concluded LPO-derived etheno-DNA adducts and LPO-modified proteins are strongly induced by oxLDL in human vascular endothelial and smooth muscle cells. This macromolecular damage may contribute to the dysfunction of arterial endothelium and the onset of atherosclerosis.
DNA ; metabolism ; Endothelium, Vascular ; cytology ; drug effects ; metabolism ; Humans ; Lipid Peroxidation ; drug effects ; Lipoproteins, LDL ; pharmacology ; Muscle, Smooth ; cytology ; drug effects ; metabolism ; Proteins ; metabolism

OBJECTIVETo study the effects of extremely low frequency electromagnetic field(ELF EMF) and its combination with lead on the antioxidant system in mouse brain and liver tissues.

METHODMice were exposed to a 50 Hz sinusoidal 0.2 mT or 6.0 mT EMF for 2 weeks. At the same time, some groups were exposed to lead(50 mg/kg). After the exposure, the antioxidant system and cell membrane fluidity in brain and liver were measured.

RESULTSMalondiadehyde(MDA) content in brain and liver increased from the control levels of (1.33 +/- 0.12) and (3.95 +/- 0.21) nmol/mg pro to (1.35 +/- 0.09) and (6.15 +/- 0.28) nmol/mg pro respectively following 0.2 mT exposure, and to (3.98 +/- 0.10) and (6.50 +/- 0.79) nmol/mg pro respectively following 6.0 mT exposure. Total antioxidant capability(T-AOC) in brain and liver decreased from the control levels of (4.39 +/- 0.48) and (2.45 +/- 0.21) U/mg pro to (3.99 +/- 0.39) and (1.92 +/- 0.32) U/mg pro respectively following 0.2 mT, and to (3.12 +/- 0.37) and (1.57 +/- 0.14) U/mg pro respectively following 6.0 mT. GSH content decreased only in liver tissue from the control level of (194.60 +/- 20.93) mg/g pro to (189.24 +/- 5.61) mg/g pro(0.2 mT) and (153.04 +/- 1.18) mg/g pro(6.0 mT). Cellular membrane fluidity decreased from the control levels of (1.396 +/- 0.040) and (2.899 +/- 0.552) to (1.224 +/- 0.190) and (1.894 +/- 0.0761) (0.2 mT), (1.159 +/- 0.179) and (1.516 +/- 0.204)(6.0 mT) respectively. Compared with single EMF exposure(6.0 mT), EMF combined with lead exposure induced remarkable increase in MDA, GSH content and T-AOC and decrease in cell membrane fluidity both in the brain and liver, and increase in SOD activity only in liver.

CONCLUSIONELF EMF might alter the metabolism of free radicals, decrease anti-oxidant capability and enhance lipid peroxidation. The combination of EMF with lead showed synergic effects on lipid peroxidation.

Animals ; Antioxidants ; metabolism ; Brain ; drug effects ; metabolism ; radiation effects ; Electromagnetic Fields ; adverse effects ; Glutathione ; analysis ; Lead ; toxicity ; Lipid Peroxidation ; drug effects ; radiation effects ; Liver ; drug effects ; metabolism ; radiation effects ; Membrane Fluidity ; drug effects ; radiation effects ; Mice ; Superoxide Dismutase ; metabolism

Hyperlipidemia is one of the most important risk factors for atherosclerosis, coronary heart disease and other cardiovascular diseases. It is the main effect of lipid-lowering drugs to reduce the plasma low-density lipoprotein or to enhance high-density lipoprotein. Niemann-Pick C1 like 1 protein (NPC1L1), acyl-coenzyme A: cholesterol acyltransferases (ACAT), ATP binding cassette transporter G member 5 and member 8 (ABCG5/G8), microsomal triglyceride transfer protein (MTP), monoacylglycerol acyltransferase, diacylglycerol acyltransferases (MAGT), peroxisome proliferator-activated receptor (PPAR), farnesoid X receptor (FXR), and proprotein convertase subtilisin/kexin type 9 (PCSK9) play key roles in the metabolism of lipid, which are regarded as the targets of anti-hyperlipidemia drugs and evidence for clinic choice of lipid-lowering drugs. These proteins are considered as breakthrough points for new lipid-lowering drug development.
Binding Sites ; Humans ; Hyperlipidemias ; drug therapy ; Hypolipidemic Agents ; pharmacology ; therapeutic use ; Lipid Metabolism ; drug effects ; Receptors, Cytoplasmic and Nuclear ; drug effects

OBJECTIVETo study the influence of selenium and fluoride on apoptosis and lipid peroxidation in human hepatocytes in vitro.

METHODSThe apoptosis, cell cycle, GSH content and lipid peroxides (LPO) level in human hepatocytes, LPO level and LDH, AST and ALT activity in cell culture supernatants were investigated after hepatocytes were incubated with selenium and/or fluoride for around 12 hours periods in vitro.

RESULTSThe percentage of hepatocyte apoptosis bodies (15.557 +/- 2.056)%, the number of cells in S phase (4.823 +/- 0.454)% and LPO level in liver tissue and supernatant [(2.884 +/- 0.589) and (3.547 +/- 0.561) nmol/L MDA/mg.prot, respectively], AST and LDH activity in supernatants (91.1 +/- 36.4 and 140.4 +/- 7.6 U/L, respectively) in the fluoride treated group was higher than the control group [(10.313 +/- 1.023)%, (3.253 +/- 0.743)%, (1.473 +/- 0.401) nmol/L MDA/mg.prot, (1.694 +/- 0.443) nmol/L MDA/mg.prot, (54.5 +/- 3.2) U/L and (126.4 +/- 2.6) U/L, respectively], The GSH content in live tissue [(4.225 +/- 0.781) microgram/mg.prot] is lower than control group [(7.595 +/- 1.042) microgram/mg.prot]. Selenium treatment reduced these kinds of toxicity of fluoride through raising GSH content, reducing LPO level, LDH and AST activity and percentage of apoptosis bodies.

CONCLUSIONSSelenium can antagonist apoptosis and lipid peroxidation of hepatocytes induced by fluoride.

Alanine Transaminase ; drug effects ; metabolism ; Apoptosis ; drug effects ; Aspartate Aminotransferases ; drug effects ; metabolism ; Cell Cycle ; drug effects ; Cells, Cultured ; Fluorides ; pharmacology ; Glutathione ; drug effects ; metabolism ; Hepatocytes ; cytology ; drug effects ; metabolism ; Humans ; L-Lactate Dehydrogenase ; drug effects ; metabolism ; Lipid Peroxidation ; drug effects ; Lipid Peroxides ; metabolism ; Selenium ; pharmacology ; Time Factors