Lipid Peroxidation In Rat Brain Homogenates Research Articles

Comparación de las propiedades antioxidantes y contenido de polifenoles de extractos acuosos de las algas marinas Bryothamnion triquetrum y Halimeda opuntia

Objective. To evaluate and compare the antioxidant activity displayed by seaweed H. opuntia and B.triquetrum using different experimental in vitro antioxidant assessment models.Material and Methods.The following techniques are utilized: DPPH, Reducing power, inhibition oflipid peroxidation and inhibition of haemolysis.Results. B. triquetrum: DPPH; IC50=1.15 ± 0.06, Reducing power (concentration 128 mg/mL), OD=2.798,inhibition of lipid peroxidation; IC50=5.09± 0.25 and inhibition of haemolysis; with 12 mg/mL; 35 %. H.opuntia: DPPH; IC50=12.34 ± 0.30 mg/mL, reducing power; OD=0.800, inhibition of lipid peroxidation;IC50=1.25± 0.31 mg/mL, inhibition of lipid peroxidation; IC50=1.25± 0.31 mg/mL and inhibition of haemolysis;82%.Conclusion. It was demonstrated that B.triquetrum extract was more effective than H. opuntia in reducingpower and DPPH assays while H.opuntia was more effective in inhibition of lipid peroxidation in ratbrain homogenates and the inhibition of red blood cell (RBC) haemolysis induced by AAPH. We discusssome aspects about their possible mechanisms of action.

In vitro Antioxidant Activity of Valeriana officinalis Against Different Neurotoxic Agents

Valeriana officinalis L. (Valerian) is widely used as a traditional medicine to improve the quality of sleep. Although V. officinalis have been well documented as promising pharmacological agent; the exact mechanisms by which this plant act is still unknown. Limited literature data have indicated that V. officinalis extracts can exhibit antioxidant properties against iron in hippocampal neurons in vitro. However, there is no data available about the possible antioxidant effect of V. officinalis against other pro-oxidants in brain. In the present study, the protective effect of V. officinalis on lipid peroxidation (LPO) induced by different pro-oxidant agents with neuropathological importance was examined. Ethanolic extract of valerian (0-60 microg/ml) was tested against quinolinic acid (QA); 3-nitropropionic acid; sodium nitroprusside; iron sulfate (FeSO4) and Fe2+/EDTA induced LPO in rat brain homogenates. The effect of V. officinalis in deoxyribose degradation and reactive oxygen species (ROS) production was also investigated. In brain homogenates, V. officinalis inhibited thiobarbituric acid reactive substances induced by all pro-oxidants tested in a concentration dependent manner. Similarly, V. officinalis caused a significant decrease on the LPO in cerebral cortex and in deoxyribose degradation. QA-induced ROS production in cortical slices was also significantly reduced by V. officinalis. Our results suggest that V. officinalis extract was effective in modulating LPO induced by different pro-oxidant agents. These data may imply that V. officinalis extract, functioning as antioxidant agent, can be beneficial for reducing insomnia complications linked to oxidative stress.

A novel series of thromboxane A2 synthetase inhibitors with free radical scavenging and anti-peroxidative activities.

A novel series of indoline derivatives with imidazole and carboxyl moieties were synthesized and evaluated for their thromboxane A2 (TXA2) synthetase inhibiting, radical scavenging and anti-peroxidative activities. Among the compounds synthesized, 3-[5-substituted-3-[2-(imidazol-1-yl)ethyl]indolin-1-yl]propionic acids showed free radical scavenging activity and inhibitory effects on lipid-peroxidation of rat brain homogenate and on arachidonate-induced TXA2-dependent aggregation of rabbit platelets. The anti-platelet and anti-peroxidative activities were related to the lipophilicity of the 5-substituent. The 5-hexyloxy derivative (13) showed about 35-fold higher inhibitory activity on TXA2 synthesis than that of ozagrel and about 100-fold higher activity on lipid peroxidation than that of alpha-tocopherol. Compound 13 showed in vivo anti-thrombotic effect in mice and ex vivo anti-peroxidative activity in rats.

ChemInform Abstract: Bioavailable Acyl-CoA: Cholesterol Acyltransferase Inhibitor with Anti-peroxidative Activity: Synthesis and Biological Activity of Novel Indolinyl Amide and Urea Derivatives.

We synthesized a series of indoline derivatives with an amide or urea moiety and examined their inhibitory effects on acyl-CoA : cholesterol acyltransferase (ACAT) activity, lipid-peroxidation and serum cholesterol levels in experimental animals. Among the derivatives synthesized, a series of N-(1-alkyl-4, 6-dimethylindolin-7-yl)-2, 2-dimethylpropanamides potently inhibited rabbit intestinal ACAT activity and lipid-peroxidation of rat brain homogenate. The effect on ACAT activity was related to the length of the alkyl chain at the 1-position of indoline. N-(4, 6-Dimethyl-1-octylindolin-7-yl)-2, 2-dimethylpropanamide hydrochloride (55) showed inhibitory effects on intestinal and hepatic ACAT activity slightly weaker than those of YM-750, and an inhibitory effect on low density lipoprotein (LDL)-peroxidation similar to that of probucol. Compound 55 also reduced serum cholesterol at 10mg/kg/d in hyperlipidemic rats and 20 mg/kg/d in normolipidemic hamsters. The plasma concentration of 55 reached 716ng/ml in dogs (10mg/kg, p.o.), which is an effect concentration against hepatic ACAT activity and LDL-peroxidation. In conclusion, compound 55 is a novel bioavailable ACAT inhibitor with anti-peroxidative activity and is thus a promising anti-atherosclerotic and anti-hyperlipidemic drug. Indoline proved to be a useful pharmacophore for molecular design of new anti-peroxidative drugs.

Bioavailable acyl-CoA: cholesterol acyltransferase inhibitor with anti-peroxidative activity: synthesis and biological activity of novel indolinyl amide and urea derivatives.

We synthesized a series of indoline derivatives with an amide or urea moiety and examined their inhibitory effects on acyl-CoA:cholesterol acyltransferase (ACAT) activity, lipid-peroxidation and serum cholesterol levels in experimental animals. Among the derivatives synthesized, a series of N-(1-alkyl-4,6-dimethylindolin-7-yl)-2,2-dimethylpropanamides++ + potently inhibited rabbit intestinal ACAT activity and lipid-peroxidation of rat brain homogenate. The effect on ACAT activity was related to the length of the alkyl chain at the 1-position of indoline. N-(4,6-Dimethyl-1-octylindolindolin-7-yl)-2,2-dimethylpropanami de hydrochloride (55) showed inhibitory effects on intestinal and hepatic ACAT activity slightly weaker than those of YM-750, and an inhibitory effect on low density lipoprotein (LDL)-peroxidation similar to that of probucol. Compound 55 also reduced serum cholesterol at 10 mg/kg/d in hyperlipidemic rats and 20 mg/kg/d in normolipidemic hamsters. The plasma concentration of 55 reached 716 ng/ml in dogs (10 mg/kg, p.o.), which is an effective concentration against hepatic ACAT activity and LDL-peroxidation. In conclusion, compound 55 is a novel bioavailable ACAT inhibitor with anti-peroxidative activity and is thus a promising anti-atherosclerotic and anti-hyperlipidemic drug. Indoline proved to be a useful pharmacophore for molecular design of new anti-peroxidative drugs.

Estrogen hormones reduce lipid peroxidation in cells and tissues of the central nervous system.

Effects of estrogen hormones on lipid peroxidation (LPO) were examined in rat brain homogenates (RBHs), hippocampal HT 22 cells, rat primary neocortical cultures, and human brain homogenates (HBHs). Dose-response curves indicated half-maximal effective concentrations (EC50) of 5.5 and 5.6 mM for iron-induced LPO in RBHs and HT 22 homogenates. Incubation of living rat primary neocortical cultures with iron resulted in an EC50 of 0.5 mM, whereas culture homogenates showed an EC50 of 1.2 mM. Estrogen hormones reduced LPO in all systems: In RBHs, estrone inhibited iron-induced LPO to 74.1 +/- 5.8% of control levels (17beta-estradiol: 71.3 +/- 0.1%) at a concentration of 10 microM. In hippocampal HT 22 cell homogenates, levels of LPO were reduced to 74.8 +/- 5.5% by estrone and to 47.8 +/- 6.2% by 17beta-estradiol. In living neocortical cultures, 17beta-estradiol decreased iron-induced LPO to 79.2 +/- 4.8% and increased the survival of cultured neuronal cells. Of the other steroid compounds tested (corticosterone, progesterone, testosterone), only progesterone decreased LPO in HT 22 cell homogenates. In HBHs, LPO was dose-dependently increased by iron concentrations from 2.7 to 6.0 mM. Incubation with estrogens resulted in a dose-dependent inhibition of LPO to 53.8 +/- 8.6% with 10 microM 17beta-estradiol, whereas estrone failed to affect iron-induced LPO to a significant extent. Nonestrogenic steroids, including hydrocortisol, did not show significant effects on LPO in HBHs.

Melatonin and vitamin E limit nitric oxide-induced lipid peroxidation in rat brain homogenates

We have investigated the level of lipid peroxidation (LPO) in rat brain homogenates in the presence of nitric oxide (NO) which was released by the addition of sodium nitroprusside (SNP) and compared it with that induced by H 2O 2. We also examined the effect of melatonin and vitamin E on the NO-induced LPO. The concentration of malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HDA) was used as an index of LPO. While both H 2O 2 and SNP increased MDA+4-HDA production in brain homogenates in a concentration-dependent manner, SNP was more potent than H 2O 2 at all concentrations tested. Both melatonin or vitamin E reduced NO-induced LPO in a dose-dependent manner in concentrations ranging from 10 μM to 10 mM. Under the in vitro conditions of this experiment, vitamin E was more efficient than melatonin in limiting NO-induced LPO in rat brain homogenates.