Dietary daidzein,but not genistein,has a hypocholesterolemic effect in non-ovariectomized and ovariectomized female Sprague-Dawley rats on a cholesterol-free diet

We compared the effects of two major isoflavones, daidzein and genistein, on lipid metabolism in rats. Daidzein (150 mg/kg diet), genistein (150 mg/kg diet), daidzein and genistein (1:1, 300 mg/kg diet), or control diets were fed to 4 groups of 6-week-old ovariectomized (Ovx) and non-Ovx Sprague Dawley rats for 4 weeks. Dietary daidzein, but not genistein, reduced serum and hepatic total cholesterol levels significantly relative to that by the control group, regardless of whether the rats had undergone ovariectomy. Genistein did not exhibit any physiological effects on lipid levels, but did affect genes involved in cholesterol metabolism. These results indicate that daidzein and genistein may influence lipid regulation via differing modes of action.     

An autoradiographic study of cellular proliferaton,DNA synthesis and cell cycle variability in the rat liver caused by phenobarbital-induced oxidative stress: The protective role of melatonin

The protective effect of melatonin against phenobarbital-induced oxidative stress in the rat liver was measured based on lipid peroxidation levels (malondialedyde and 4-hydroxyalkenals). Cellular proliferation, DNA synthesis and cell cycle duration were quantitated by the incorporation of ³H-thymidine, detected by autoradiography, into newly synthesized DNA. Two experiments were carried out in this study, each on four equal-sized groups of male rats (control, melatonin [10 mg/kg], phenobabital [20 mg/kg] and phenobarbital plus melatonin). Experiment I was designed to study the proliferative activity and rate of DNA synthesis, and measure the levels of lipid peroxidation, while experiment II was for cell cycle time determination. Relative to the controls, the phenobarbital-treated rats showed a significant increase (P < 0.01) in the lipid peroxidation levels (30.7%), labelling index (69.4%) and rate of DNA synthesis (37.8%), and a decrease in the cell cycle time. Administering melatonin to the phenobarbital-treated rats significantly reduced (P < 0.01) the lipid peroxidation levels (23.5%), labelling index (38.2%) and rate of DNA synthesis (29.0%), and increased the cell cycle time. These results seem to indicate that the stimulatory effect of phenobarbital on the oxidized lipids, proliferative activity, kinetics of DNA synthesis and cell cycle time alteration in the liver may be one of the mechanisms by which the non-genotoxic mitogen induces its carcinogenic action. Furthermore, melatonin displayed powerful protection against the toxic effect of phenobarbital.     

Effects of soluble corn bran arabinoxylans on cecal digestion, lipid metabolism, and mineral balance (Ca, Mg) in rats

The effects of soluble corn bran arabinoxylans on cecal digestion, lipid metabolism, and mineral utilization [calcium (Ca) and magnesium (Mg)] were investigated in rats adapted to semipurified diets. The diets provided either 710 g/kg wheat starch alone (control) or 610 g/kg wheat starch plus 100 g/kg corn soluble fiber (arabinoxylans) and either 0 or 2 g/kg cholesterol (control + cholesterol and arabinoxylans + cholesterol, respectively). Compared with rats fed the control diets, rats fed the arabinoxylan diets had significant cecal hypertrophy (+50% after 3 days of the fiber adaptation) and an accumulation of short-chain fatty acids, especially propionic acid (up to 45% in molar percentage). Arabinoxylans enhanced the cecal absorption of Ca and Mg (from 0.07 to 0.19 micromol/min for Ca and from 0.05 to 0.23 micromol/min for Mg). Mg balance was enhanced by arabinoxylans (+25%). The arabinoxylan diet markedly reduced the cholesterol absorption from 50% of ingested cholesterol in controls up to approximately 15% in rats adapted to the arabinoxylans diet. Arabinoxylans were effective in lowering plasma cholesterol (approximately -20%). There was practically no effect of the diets on cholesterol in d > 1.040 lipoproteins (high density lipoproteins) whereas arabinoxylans were very effective in depressing cholesterol in d < 1.040 lipoproteins (especially in triglyceride-rich lipoproteins). Corn fermentable fiber decreased the accumulation of cholesterol in the liver. In parallel, the arabinoxylan diet counteracted the downregulation of 3-hydroxy-3-methylglutaryl-CoA by cholesterol. These data suggest that arabinoxylans may have a great impact on intestinal fermentation, mineral utilization, and cholesterol metabolism.     

Cadmium influence on lipid metabolism in Sprague–Dawley rats through linoleic acid and glycerophospholipid metabolism pathways

Cadmium (Cd) is widely distributed in the environment and easy adsorbed by living organisms with adverse effects. Exposure to Cd-contaminated food may disrupt lipid metabolism and increase human health risk. To study the perturbation effect of Cd on lipid metabolism in vivo, 24 male Sprague–Dawley (SD) rats were randomly assigned four groups and treated by Cd chloride solution (0, 1.375 mg/kg, 5.5 mg/kg, 22 mg/kg) for 14 days. The characteristic indexes of serum lipid metabolism were analyzed. Afterwards, untargeted metabolomics analysis was applied to explore the adverse effects of Cd on rats by liquid chromatography coupled with mass spectrometry (LC-MS). The results revealed that Cd exposure obviously decreased the average serum of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) and caused an imbalance of endogenous compounds in the 22 mg/kg Cd-exposed group. Compared with the control group, 30 metabolites with significant differences were identified in the serum. Our results indicated that Cd caused lipid metabolic disorders in rats by disrupting linoleic acid and glycerophospholipid metabolism pathways. Furthermore, there were three kinds of remarkable differential metabolites—9Z,12Z-octadecadienoic acid, PC(20:4(8Z,11Z,14Z,17Z)/0:0), and PC(15:0/18:2(9Z,12Z)), which enriched the two significant metabolism pathways and could be the potential biomarkers.     

Effect of α-Lipoic Acid on Lipid Profile in Rats Fed a High-Fructose Diet

This study investigated the effect of administration of α-lipoic acid (LA) on lipid metabolism in high fructose–fed insulin-resistant rats. High-fructose feeding (60 g/100 g diet) to normal rats resulted in a significant increase in the concentrations of cholesterol, triglycerides (TGs), free fatty acids (FFAs), and phospholipids in plasma, liver, kidney, and skeletal muscle. Reduced activities of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) and increased activity of the lipogenic enzyme hydroxymethylglutaryl–coenzyme A (HMG-CoA) reductase were observed in plasma and liver. High-density lipoprotein cholesterol (HDL-C) was significantly lowered and very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) were significantly elevated. Treatment with LA (35 mg/kg body weight intraperitoneal) reduced the effects of fructose. The rats showed near-normal levels of lipid components on plasma and tissues. Activities of key enzymes of lipid metabolism were also restored to normal values. Cholesterol distribution in the plasma lipoproteins was normalized, resulting in a favorable lipid profile. This study demonstrates that LA can alter lipid metabolism in fructose-fed insulin-resistant rats and may have implications in the treatment of insulin resistance.     

The profile of urinary metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rats is determined by its pulmonary metabolism.

Metabolism of the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in rats was compared to metabolism in primary lung and liver cells. Untreated rats and rats pretreated with phenobarbital, acetone or phenethyl isothiocyanate (PEITC) were used for all experiments. Also the influence of [-]-1-methyl-2-[3-pyridyl]-pyrrolidine (nicotine) administered concomitantly with NNK, or incubated with isolated cells, upon NNK metabolism was investigated and found to be only marginal upon alpha-hydroxylation and pyridine N-oxidation in vivo. In hepatocytes nicotine inhibited NNK pyridine N-oxidation, alpha-hydroxylation and glucuronidation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), whereas in lung cells the influence of nicotine was not as pronounced. In vivo phenobarbital induced alpha-hydroxylation and pyridine N-oxidation. In vitro the effects of the modulators were most pronounced upon hepatocytes, where phenobarbital greatly induced pyridine N-oxidation and PEITC inhibited alpha-hydroxylation. NNAL was conjugated to its beta-glucuronide in lung cells at four times higher rates than in hepatocytes. The ratios of the sum of N-oxides to the sum of alpha-hydroxylation products in vivo were similar to those in lung cells, especially at low NNK concentrations (1 microM), while in hepatocytes alpha-hydroxylation was more pronounced. The same correlation of metabolism in isolated lung cells with whole rats was observed if oxidative NNAL metabolism was related to oxidative NNK metabolism. Here hepatocytes showed a much higher formation of NNAL oxidation products than either lung cells formed, or rats excreted in urine. This was true despite a lower rate of metabolism in the lung than in liver if based on cell number, the rate based on mg protein was four times higher in lung than liver. Only after phenobarbital treatment was the contribution of hepatic metabolism to excreted metabolites important. In conclusion the lung which is also the target of NNK carcinogenesis, and not the liver, is the organ with the most important contribution to NNK and NNAL metabolism at concentrations relevant to human exposure.     

Attenuation of low dose phenobarbital induction of hepatic microsomal aminopyrine N-demethylase activity in rats by cimetidine

Cimetidine, a substituted imidazole, is an inhibitor of hepatic cytochrome P-450-mediated drug metabolism in rats and humans. We investigated the effect of cimetidine on phenobarbital induction of hepatic microsomal aminopyrine N-demethylase activity in the rat. Phenobarbital induction of aminopyrine N-demethylase was log-linear in the range of 1-6 mg/kg/day and the ED50 was approximately 3 mg/kg/day. Cimetidine 75 mg/kg (four times a day) attenuated the induction of aminopyrine N-demethylase activity by 58% in low dose (3 mg/kg/day) but not in high dose (40 mg/kg/day) phenobarbital treated rats. This result could not be explained by residual inhibition of enzyme activity by cimetidine and suggests that cimetidine affects the induction of hepatic cytochrome P-450 by low dose phenobarbital.     

The influence of dietary vitamin E, fat, and methionine on blood cholesterol profile, homocysteine levels, and oxidizability of low density lipoprotein in the gerbil

A 90-day feeding study with gerbils was conducted to evaluate the influence of dietary vitamin E levels (25 mg/kg diet, 75 mg/kg, 300 mg/kg, and 900 mg/kg), two levels of dietary methionione (casein or casein+L-methionine (1% w/w)) and two sources of lipid (soybean oil [20%] or soybean oil [4%]+coconut oil [16%, 1:4 w/w]) upon serum lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol). In addition, this study examined the effects of diet-induced hyperhomocysteinemia and supplemental dietary vitamin E on the oxidation of low density lipoproteins. Tissue vitamin E (heart, liver, and plasma) demonstrated a dose response (P≤0.001) following the supplementation with increasing dietary vitamin E (25, 75, 300, and 900 mg/kg). In addition, tissue vitamin E levels were found to be higher (P≤0.001) in those animals receiving a combination of coconut oil+soybean oil as compared to the group receiving soybean oil solely. Blood cholesterol profiles indicated an increase (P≤0.001) in total cholesterol and LDL cholesterol by the influence of saturated fat and supplemental methionine. Low-density lipoprotein cholesterol profile demonstrated a reduction (P≤0.001) at the higher dietary vitamin E levels (300 and 900 mg/kg) as compared to the 25 mg/kg and 75 mg/kg dietary vitamin E. Plasma protein carbonyls were not influenced by dietary vitamin E nor by supplemental methionine intake. In vitro oxidation of LDL showed that vitamin E delayed the lag time of the oxidation phase (P≤0.001) and reduced total diene production (P≤0.001). On the contrary, supplemental methionine decreased (P≤0.001) the delay time of the lag phase, whereas total diene production was increased (P≤0.001). Plasma lipid hydroperoxides were significantly reduced (P≤0.05) with supplemental dietary vitamin E, whereas supplemental L-methionine (1%) resulted in a significant (P≤0.05) increase in lipid plasma hydroperoxide formation. Plasma homocysteine was elevated (P≤0.001) with supplemental dietary L-methionine (1%) as well as the inclusion of dietary saturated fat. The present data showed that 1) a combination of dietary lipids (saturated and unsaturated fatty acids) as well as vitamin E and methionine supplementation altered blood cholesterol lipoprotein profiles; 2) in vitro oxidation parameters including LDL (lag time and diene production) and plasma hydroperoxide formations were affected by vitamin E and methionine supplementation; and 3) plasma homocysteine concentrations were influenced by supplemental methionine and the inclusion of dietary saturated fat.     

Endurance training increased HDL cholesteryl ester metabolism in rats

We studied the effects of endurance training on the metabolism of high-density lipoprotein (HDL, 1.063 less than density less than 1.15 kg/l) cholesteryl ester and proteins in rats fed a cholesterol-rich (1%) semipurified diet. The HDL were labeled with 131I in the apoproteins and with cholesteryl-[1-14C]oleate in the esters. The HDL were intravenously administered to endurance-trained (n = 10) and cage-sedentary (n = 10) rats. Blood samples were taken over the next 36 h while the rats were conscious and feeding. The trained rats had higher plasma HDL cholesterol (0.72 vs. 0.28 mM) and HDL apoprotein (461 vs. 267 mg/l) concentrations than the sedentary rats. The production or disposal rate of HDL cholesteryl ester was higher in the trained rats (1.36 mumol/h) than in the sedentary rats (0.72 mumol/h), whereas the production or disposal rate of HDL apoproteins was similar in the trained (0.64 mg/h) and sedentary (0.60 mg/h) rats. The residence time of the HDL cholesteryl esters (4.72 +/- 0.22 vs. 3.37 +/- 0.21 h) and HDL apoprotein (7.65 +/- 0.36 vs. 4.55 +/- 0.28 h) was longer for the trained than for the sedentary rats. These data indicate that endurance training resulted in a significant change in the metabolism of HDL cholesteryl esters and apoproteins as well as an increase in their concentrations.     

Dexamethasone treatment in the newborn rat: fatty acid profiling of lung, brain, and serum lipids.

Dexamethasone is used as treatment for a variety of neonatal syndromes, including respiratory distress. The present study utilized the power of comprehensive lipid profiling to characterize changes in lipid metabolism in the neonatal lung and brain associated with dexamethasone treatment and also determined the interaction of dexamethasone with hypoxia. A 4-day tapering-dose regimen of dexamethasone was administered at 0800 on postnatal days 3 (0.5 mg/kg), 4 (0.25 mg/kg), 5 (0.125 mg/kg), and 6 (0.05 mg/kg). A subgroup of rats was exposed to hypoxia from birth to 7 days of age. Dexamethasone treatment elicited numerous specific changes in the lipid profile of the normoxic lung, such as increased concentrations of saturated fatty acids in the phosphatidylcholine and cholesterol ester classes. These increases were more profound in the lungs of hypoxic pups. Additional increases in cardiolipin concentrations were also measured in lungs of hypoxic pups treated with dexamethasone. We measured widespread increases in serum lipids after dexamethasone treatment, but the effects were not equivalent between normoxic and hypoxic pups. Dexamethasone treatment in hypoxic pups increased 20:4n6 and 22:6n3 concentrations in the free fatty acid class of the brain. Our results suggest that dexamethasone treatment in neonates elicits specific changes in lung lipid metabolism associated with surfactant production, independent of changes in serum lipids. These findings illustrate the benefits of dexamethasone on lung function but also raise the potential for negative effects due to hyperlipidemia and subtle changes in brain lipid metabolism.     

In vivo effects of 3-methylcholanthrene, phenobarbital, pyrethrum and 2,4,5-T isooctylester on liver, lung and kidney microsomal mixed-function oxidase system of guinea-pig: a comparative study

The optimum conditions (pH, microsomal protein amount and substrate concentration) of guinea-pig liver, lung and kidney microsomal aniline 4-hydroxylase, ethylmorphine N-demethylase and benzo[a]pyrene hydroxylase activities were determined. Male guinea-pigs weighing 500-700 g were administered 3-methylcholanthrene (25 mg/kg, i.p. 3 days), phenobarbital (75 mg/kg, i.p. 3 days), pyrethrum (120 mg/kg, i.p. 2 days) and 2,4,5-T isooctylester (200 mg/kg, i.p. 3 days). 3-Methylcholanthrene treatment caused significant increases in liver microsomal benzo[a]pyrene hydroxylase and kidney microsomal aniline 4-hydroxylase activities. However, with phenobarbital treatment the only significant increase was observed in liver microsomal ethylmorphine N-demethylase activity. Pyrethrum treatment decreased kidney microsomal ethylmorphine N-demethylase activity significantly. 2,4,5-T isooctylester treatment increased liver microsomal aniline 4-hydroxylase and lung microsomal ethylmorphine N-demethylase activities significantly. Liver microsomal NADPH-cytochrome c reductase activity was increased significantly by phenobarbital and pyrethrum treatment. The other treatments did not cause any significant changes in microsomal NADPH-cytochrome c reductase activities of liver, lung and kidney. Cytochrome P-450 content of guinea-pig liver microsomes were increased significantly about 2.5-fold and 2-fold by treatment with 3-methylcholanthrene and phenobarbital, respectively. 3-Methylcholanthrene also caused 1 nm spectral shift in the absorption maxima of CO difference spectrum of the dithionite-reduced liver microsomal cytochrome P-450, forming P-449.     

Protective effect of Morus rubra L. leaf extract on diet-induced atherosclerosis in diabetic rats

The antiatherosclerotic effect of aqueous leaves extract of Morus rubra was studied in streptozotocin-induced diabetic rats fed with atherosclerotic (Ath) diet [1.5 ml olive oil containing 8 mg (3, 20,000 IU) vitamin D2 and 40 mg cholesterol] for 5 consecutive days. A short-term toxicity assessment was also conducted in healthy rats to examine toxic effects of the extract. Oral administration of extract to diabetic rats (100, 200 and 400 mg/kg body weight per day for a period of 30 days) produced significant (p<0.001) fall in fasting blood glucose (FBG) in a dose-dependent manner. Treatment with the extract (400 mg/kg) showed significant (p<0.001) improvement in body weight and serum lipid profile i.e., total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol, when compared with diabetic control. Endothelial dysfunction parameters (sVCAM-1, Fibrinogen, total NO levels and oxidized LDL), apolipoprotein A and apolipoprotein B were significantly (p<0.001) reversed to near normal, following treatment with the extract. Thus, our study shows that aqueous leaf extract of Morus rubra (400 mg/kg) significantly improves the homeostasis of glucose and fat and possesses significant anti-atherosclerotic activity.     

Anti-obesity, anti-diabetic, and lipid lowering effects of the thyroid receptor beta subtype selective agonist KB-141

Selective thyroid hormone receptor subtype-beta (TRbeta) agonists have received attention as potential treatments for hypercholesterolemia and obesity, but have received less attention as treatments for diabetes, partly because this condition is not improved in thyroid hormone excess states. The TRbeta selective agonist KB-141 induces 5-10% increases in metabolic rate and lowering of plasma cholesterol levels without tachycardia in lean rats, unlike the major active thyroid hormone, T(3). In the current study, we determined whether KB-141 promotes weight loss in obese animals and whether it exhibits anti-diabetogenic effects. Body weight, adiposity (DEXA), and lipid levels were examined following p.o. administration of KB-141 to obese Zucker fa/fa rats at 0.00547-0.547mg/kg/day for 21 days, and in ob/ob mice at 0.5mg/kg/day KB-141 for 7 days. In rats, KB-141 reduced body weight by 6 and 8%, respectively, at 0.167 and 0.0547mg/kg/day without tachycardia and adiposity was reduced at 0.167mg/kg/day (5-6%). In ob/ob mice, KB-141 lowered serum cholesterol (35%), triacylglycerols (35%) and both serum and hepatic free fatty acids (18-20%) without tachycardia. Treatment of ob/ob mice with KB-141 (0.0547 or 0.328mg/kg/day over 2 weeks) improved glucose tolerance and insulin sensitivity in a dose-dependent manner with no effect on heart rate. Thus, KB-141 elicits anti-obesity, lipid lowering and anti-diabetic effects without tachycardia suggesting that selective TRbeta activation may be useful strategy to attenuate features of the metabolic syndrome.     

In vitro age-dependent incorporation of [1-14C]acetate into lipid subclasses in rat ventral prostate

The [1-14C]acetate incorporation into different lipid subclasses by the rat prostate gland was lineal between 20 and 80 mg of wet tissue. The in vitro [1-14C]acetate incorporation into lipid subclasses was a development-dependent process. The highest values of [1-14C]acetate incorporation into triacylglycerols, free cholesterol and esterified cholesterol were observed at puberty, but radioactivity incorporation into phospholipids was similar in both prepuberty and puberty, then decreasing in maturity. The relationship between triacylglycerols, free cholesterol and esterified cholesterol with respect to total lipids was about 12, 10 and 3.5%, respectively, values being maintained during the animal development. The in vitro [1-14C]acetate incorporation into lipid subclasses in castrated rats decreased considerably as compared with normal rats.     

6-Substituted 2,2-bis(fluoromethyl)-benzopyran-4-carboxamide K+ channel openers

In the course of our study to find an ideal antihypertensive potassium channel opener (KCO), N-(2-cyanoethyl)-2,2-bis(fluoromethyl)-6-pentafluoroethyl-2H-1-ben zopyran-4-carboxamide (13f, KC-515) showed a highly potent, slow and long-lasting antihypertensive effect with reduced reflex tachycardia, together with the beneficial effects of KCO such as improvement in lipid metabolism. These profiles identify KC-515 as a potential candidate. In conscious spontaneously hypertensive rats (SHR), the onset of the hypotensive effect of KC-515 (13f) was gradual and the maximum response was attained at around 6 h after dosing. The duration of action was over 18 h for 0.1 mg/kg. When administered to Zucker rats for 2 weeks with 0.03-0.3 mg/kg po range in the antihypertensive doses in hypertensive rat models, KC-515 (13f) significantly and dose-dependently reduced serum triglycerides to less than 70% of control without affecting total cholesterol.     

Antigastrolesive, gastric antisecretory, diarrheagenic and mucus-stimulating effects in rats following topically applied rioprostil, a synthetic prostaglandin E1 analog

Prostaglandins may have many biological actions including hypotensive and antipeptic ulcer activity. The purpose of this investigation was to determine if the primary alcohol prostaglandin E1 analog rioprostil1 prevents ethanol-induced gastric lesions (antigastrolesive activity), inhibits gastric acid secretion (antisecretory activity), or causes diarrhea in rats when administered topically, and to compare these responses to the effect of rioprostil following enteral (oral or intraduodenal) administration. Rioprostil exhibited antigastrolesive activity in rats when administered either orally or when applied topically. The topical antigastrolesive potency of rioprostil against ethanol-induced lesions [ED50 = 3.7 (0.5-12) micrograms/kg] was similar to its oral potency [ED50 = 1.9 (1.7-2.2) micrograms/kg]. In 4 hr pylorus-ligated rats, topically administered rioprostil inhibited total gastric acid output with a potency [ED50 = 5.1 (2.6-24) mg/kg] similar to intraduodenal administration [ED50 = 3.7 (2.8-5.3) mg/kg]. In addition, in these rats rioprostil increased mucin levels and did not cause dermal irritation. Finally, the incidence of diarrhea was lower when rioprostil was applied topically than when given orally with a 16-fold difference in potency between these two routes of administration. These data show that when rioprostil is applied via the skin it has antigastrolesive, gastric antisecretory and mucus stimulatory effects in rats equal to enteral administration, and a diarrheagenic potency lower than following oral administration. This profile suggests that topical administration of rioprostil may be a useful means of delivery for clinical treatment of peptic ulcer disease.     

Effects of AH-9700, (+)-pentazocine, DTG and oxybutynin on micturition in anesthetized rats with acetone-induced cystitis

We investigated the effects of AH-9700 (1-[2-(3,4-dihydro-6,7-dimethyl-2-naphthalenyl)ethyl] pyrrolidine fumarate; a novel sigma receptor ligand), (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG) (two typical sigma receptor ligands), and oxybutynin (a currently used anti-pollakiuria drug) on cystometrograms in anesthetized rats with 30% acetone-induced cystitis. Compared to sham-treated rats, acetone-treated cystitis models exhibited an increase in urinary frequency during continuous filling cystometry. Intravenous administration of AH-9700 (1-5 mg/kg), (+)-pentazocine or DTG to the rats with cystitis dose-dependently prolonged micturition intervals and increased the micturition threshold pressure. Oxybutynin (1 mg/kg. i.v.) also extended micturition intervals, but decreased the micturition pressure. These results indicate that AH-9700, (+)-pentazocine and DTG improve abnormal frequent urination caused by acetone-induced cystitis in a manner different from that of oxybutynin.     

Antilipoperoxidative and antioxidant effects of S-allyl cysteine sulfoxide on isoproterenol-induced myocardial infarction in Wistar rats

Our study evaluates the preventive effect of S-allyl cysteine sulfoxide (SACS) on lipid peroxidative products and enzymic and nonenzymic antioxidants in isoproterenol (ISO) induced myocardial infarction in rats. The male Wistar rats were rendered myocardial infarction by ISO (150 mg kg(-1), once a day for two days). The concentrations of thiobarbituric acid reactive substances and lipid hydroperoxides were increased in hearts from ISO-treated rats, whereas the content of enzymic and nonenzymic antioxidants were declined in rats administered ISO. Oral pretreatment with SACS (40 mg kg(-1) and 80 mg kg(-1) daily for a period of 35 days) significantly (p < 0.05) decreased the lipid peroxidative products and significantly (p < 0.05) increased antioxidants in ISO-induced rats. Oral administration of SACS (40 mg kg(-1) and 80 mg kg(-1)) did not show any significant effect in normal rats. Thus, the present study shows that SACS exhibits antilipoperoxidative and antioxidant effects in experimental myocardial infarction.     

裂殖壶藻藻油DHA对高脂饮食诱导肥胖小鼠的影响

【目的】肥胖症是一种慢性代谢类疾病,具有较高的发病率和高危后果。研究表明,n-3多不饱和脂肪酸(n-3 Polyunsaturated fatty acids,n-3 PUFAs),特别是二十二碳六烯酸(Docosahexaenoic acid,DHA)对与肥胖症相关疾病有较好的防治效果,对体内脂质代谢有重要的调节作用。探讨裂殖壶藻(Schizochytrium sp.)藻油DHA对高脂饮食诱导肥胖小鼠体重、脂肪组织重量、血脂、肝和脂肪组织病理形态和脂质代谢相关基因表达的影响。【方法】通过高脂饮食建立小鼠肥胖模型,以体重增幅15%为标准分出肥胖小鼠。试验共分五组:(1)低脂对照组;(2)高脂模型组;(3)高脂+低剂量藻油组(50 mg DHA/kg);(4)高脂+中剂量藻油组(100 mg DHA/kg);(5)高脂+高剂量藻油组(200 mg DHA/kg)。其中,藻油处理组灌服相应剂量藻油,低脂对照组和高脂模型组灌胃同等体积玉米油。处理9周后,腹腔麻醉,摘眼球取血并分离血清,测血清中甘油三酯、胆固醇和高密度脂蛋白含量;之后处死小鼠,分离附睾、肾周和肠系膜脂肪组织及肝脏,称湿重;附睾脂肪和肝组织切片进行HE染色,观察病理变化情况;利用RT-PCR检测附睾脂肪组织中激素敏感脂酶(Hormone sensitive lipase,HSL)基因的m RNA表达情况。【结果】藻油处理组小鼠体重没有显著下降,但是腹部脂肪重量显著降低、脂肪细胞体积明显小于高脂模型组;同时血清中甘油三酯、胆固醇含量显著降低,肝组织异位脂肪堆积明显减少;脂肪组织中HSL基因的表达水平显著提高。【结论】裂殖壶藻藻油DHA处理能显著降低高脂饮食导致的小鼠腹部脂肪积累并改善血脂,可能有利于肥胖症的防治。     

Serum Lipid Profile in Subjects with Traumatic Spinal Cord Injury

ResultsCases without preserved motor function (AIS A or B) had lower total and HDL cholesterol than the others (-11.4 [-21.5, -1.4] mg/dL total cholesterol and -5.1 [-8.8, -1.4] mg/dL HDL-c), and cases with all-limb involvement had lower total, HDL, and LDL cholesterol than those with only lower-limb involvement (-14.0 [-24.6, -3.4] mg/dL total cholesterol, -4.1 [-8.0, -0.2] mg/dL HDL-c, and -10.0 [-19.7, -0.3] mg/dL LDL-c) (all p<0.05). No association was found between lipid concentrations and time since injury. Concentrations of lipid subfractions and triglycerides in SCI subjects were lower than in sex- and age-stratified values from the reference sample.ConclusionA high degree of neurological involvement in SCI (anatomically higher lesions and AIS A or B) is associated with lower total cholesterol and HDL-c.