Effect of mercury chloride on the level of lipids and products of their peroxidation in rat vital organs

The influence of mercury chloride on peroxidation processes of lipids and level of common lipids, phospholipids and spectrum of neutral lipids in liver, heart, lung and kidney of rats has been investigated. Administration of mercury chloride in a dose 0.7 mg/100 g of body weight to animals has invoked accumulation of lipids peroxide products in fractions of neutral lipids and phospholipids so it testifies the development of oxidative stress. Decrease of the most sensitive to oxidation fractions in the early stages of oxidative stress development and increase of free cholesterol and its ethers content in kidney and free cholesterol in the heart in more later terms as a result of mercury chloride administration have been revealed.     

Effect of oral methionine and vitamin E on blood lipid peroxidation in vitamin B6 deficient rats

Lipid peroxidation in blood of vitamin B6 deficient rats was significantly increased when compared to pair-fed controls. The observed increased lipid peroxidation in vitamin B6 deficiency was correlated with high levels of lipids, metal ions and low levels of antioxidants, alpha-tocopherol, ascorbic acid and reduced GSH. Supplementation of methionine or vitamin E along with the vitamin B6 deficient diet restored the levels of antioxidants to near normal and also protected against oxidative stress. However plasma TBARS level as well as total lipids were still elevated in M-B6 diet fed rats and normalized in E-B6-d rats.     

Evidence for Oxidative Stress in the Subthalamic Nucleus in Progressive Supranuclear Palsy

Increased free radical production and oxidative stress have been proposed as pathogenic mechanisms in several neurodegenerative disorders. Free radicals interact with biological macromolecules, such as lipids, which can lead to lipid peroxidation. A well-established marker of oxidative damage to lipids is malondialdehyde (MDA). We measured tissue MDA levels in the subthalamic nucleus (STN) and cerebellum from 11 progressive supranuclear palsy (PSP) cases and 11 age-matched control cases using sensitive HPLC techniques. In PSP, a significant increase in tissue MDA levels was observed in the STN when compared with the age-matched control group. By contrast, no significant difference between tissue MDA content was observed in cerebellar tissue from the same PSP and age-matched control cases. These results indicate that lipid peroxidation may play a role in the pathogenesis of PSP.     

Importance of the polyunsaturated fatty acid to vitamin E ratio in the resistance of rat lung microsomes to lipid peroxidation

Rat lung microsomes and liposomes made from isolated lung microsomal lipids were found to be much more resistant to lipid peroxidation than those from liver in both enzymatic and nonenzymatic systems. The polyunsaturated fatty acid (PUFA) content of isolated lung microsomal lipids was 28% of total fatty acids, while liver was 54%. The vitamin E (α-tocopherol) content of isolated lung microsomal lipids was 2.13 nmol/μmol lipid phosphate and that of liver was 0.43. Individually, neither the lower PUFA content nor higher vitamin E levels could account for the resistance of lung microsomal lipids to peroxidation. Distearoyl-L-a-phosphatidylcholine and/or α-tocopherol were added to liver microsomal lipids to achieve different PUFA to vitamin E ratios at PUFA contents of 28% or 54%, and the resulting liposomes were subjected to an NADPH-dependent lipid peroxidation system utilizing cytochrome P450 reductase, EDTA-Fe⁺³, and ADP-Fe⁺³. Liposomes having PUFA to vitamin E ratios less than approximately 250 nmol PUFA/nmol vitamin E were resistant to peroxidation, whereas lipid peroxidation, as evidenced by malondialdehyde production, occurred in liposomes having higher ratios. When lipid peroxidation occurred, 40%–60% of the liposomal vitamin E was irreversibly oxidized. Irreversible oxidation did not occur in the absence of lipid peroxidation. These studies indicated that the low PUFA to vitamin E ratio in lung microsomes and isolated microsomal lipids was sufficient to account for the observed resistance to lipid peroxidation.     

Catalase activity in the myocardium during stress in adult and aged rats]

The study of catalase myocardium activity at stress in adult and old rats has been performed. It has been revealed that the formation of immobilization stress is accompanied by the enzyme activity stimulation. The expression of this effects is more significant in adult animals. Experimental data concerning the possible role of peroxidation lipids in myocardium catalase stress activation and its age modulation are given.     

Molecular mechanisms of stress

Data on molecular mechanisms of stress are presented (appearance of stress-proteins in the blood, as well as products of peroxidation products of lipids, and changes of the cell ion balance in stress). Particular accent was made on appearance of endogenous inhibiting agents in the blood: Na+,K+-ATPase, in response to extremal factor actions inducing stress.     

Effect of thyroid status on lipid composition and peroxidation in the mouse liver

In order to analyze the possible relationship between metabolic rate and oxidative stress, OF1 female mice were rendered hyper- or hypothyroid for 4–5 weeks by administration of 0.0012%l-thyroxine (T₄) or 0.05% 6-n-propyl-2-thiouracil (PTU), respectively, in their drinking water. Treatment with T₄ resulted in increased basal metabolic rate measured by oxygen consumption and liver cytochrome oxidase activity without altering the glutathione redox system. Endogenous lipid peroxidation, sensitivity to lipid peroxidation and fatty acid unsaturation were decreased in the hyperthyroid group. Hypothyroidism also decreased phosphatidylcholine and cardiolipin fatty acid unsaturation but not in total lipids, and thus lipid peroxidation was not altered. Cardiolipin, a mainly mitochondrial lipid, was the most profoundly altered fraction by both hyper- and hypothyroidism. It is suggested that the lipid changes observed in hyperthyroid animals can protect them against an increased oxidative attack to tissue lipids due to their increased mitochondrial activities.     

Eicosanoids in preeclampsia

Preeclampsia is characterized by an imbalance between two cyclooxygenase metabolites of arachidonic acid, thromboxane and prostacyclin, that favors thromboxane. Because of the biologic actions of these two eicosanoids, this imbalance might explain major clinical symptoms of preeclampsia, such as hypertension, platelet aggregation and reduced uteroplacental blood flow. In the maternal circulation, this imbalance is primarily manifested by decreased production of prostacyclin by endothelial cells. Platelet thromboxane synthesis is only increased in severe preeclampsia. In the placenta and in leukocytes, the imbalance is exacerbated by increased production of thromboxane coupled with decreased production of prostacyclin in both mild and severe preeclampsia. Longitudinal measurements of urinary metabolites of thromboxane and prostacyclin reveal that the thromboxane/prostacyclin imbalance predates the onset of clinical symptoms of preeclampsia. The imbalance between thromboxane and prostacyclin is most likely caused by oxidative stress, which is manifest in preeclampsia by increased lipid peroxidation and decreased antioxidant protection. Oxidative stress may drive this imbalance because lipid peroxides activate the cyclooxygenase enzyme to increase thromboxane synthesis, but at the same time they inhibit prostacyclin synthase to decrease prostacyclin synthesis. Low-dose aspirin therapy (50-150 mg/day) has been considered for the prevention of preeclampsia because it selectively inhibits thromboxane synthesis. Several studies reported dramatic decreases in the incidence of preeclampsia with low-dose aspirin therapy. However, two large multicenter studies reported only modest decreases, which dampened enthusiasm. The two large studies were "intent to treat" studies which included patients who were noncompliant and who discontinued the use of aspirin. In one of the studies for which compliance statistics were available only 53% of the aspirin group had a compliance rate greater than 75%, which raises a question as to whether the effectiveness of aspirin was being tested. Low-dose aspirin therapy should not yet be dismissed for the prevention of preeclampsia, but be reconsidered with emphasis on compliance using doses of aspirin in the range of 100-150 mg/day combined with antioxidants.     

The effect of synthetic enkephalins on prostaglandin synthesis and lipid peroxidation in the isolated heart during the activation of free-radical processes]

The system Fe(2+)-ascorbate was used for lipid peroxidation (LPO) activation in isolated heart tissue. The stimulation of free radical processes in the myocardium caused a rise in the level of LPO products and a significant lowering of that of prostacyclin. Intravenous injection of synthetic analogues of enkephalins before LPO activation inhibited LPO and resulted in prostacyclin synthesis normalization. The addition of peptides under study into perfusion solution led to a decrease in LPO primary products level and in thromboxane synthesis.     

The role of thylakoid lipids in the photodamage of photosynthetic activity

The effect of excess light at 10 or 30°C under aerobic or low O₂ condition on peroxidation of thylakoid lipids and primary photochemistry of photoinsynthesis was studied in wheat ( Triticum aestivum L. cv. HD 2329). Photoinhibitory damage to photosythesis was directly proportional to the peroxidation of thylakoid lipids. Photoinhibitory treatment given under low O₂ conditions resulted in significantly less peroxidation of the primary photochemistry of photosythesis measured using chlorophyll fluorescence and photosythetic electron trasport. Short term recovery of F_v/F_m ratio was fast while thylakoid lipids did not show much recovry. However, recovery (of F_v/F_m ratio and thylakoid lipids) was almost complete within 12 h after photoinhibition treatment. A possible relationship between peroxidation of thylakoid lipids and photodamage to photosynthesis is discussed.     

Advantages and limitation of BODIPY as a probe for the evaluation of lipid peroxidation and its inhibition by antioxidants in plasma

Oxidative stress and the role of antioxidants are currently one of the most important subjects in the field of life science. In the present study, we assessed the oxidation of plasma lipids induced by free radicals and its inhibition by antioxidants with a fluorescence probe BODIPY. Vitamin E and C-depleted plasma was used to evaluate the inherent action of several antioxidants. BODIPY reacted with free radicals in plasma to emit fluorescence (ex. 510 nm, em. 520 nm), which was suppressed by the antioxidants in a concentration-dependent manner. However, the suppression of fluorescence emission by antioxidants did not always correlate quantitatively with the suppression of lipid peroxidation. For example, alpha-tocopherol suppressed BODIPY fluorescence but enhanced the peroxidation of plasma lipids in the absence of ascorbic acid. 2,2,5,7,8-Pentamethyl-6-chromanol, a vitamin E analogue without a phytyl side chain, almost completely suppressed both fluorescence emission and lipid peroxidation in the plasma. These results show that BODIPY can be used as a convenient probe for radical scavenging, but that care should be taken for the evaluation of antioxidant capacity.     

Radical acetoacetate oxidation by myeloperoxidase, lactoperoxidase, prostaglandin synthetase, and prostacyclin synthetase: implications for atherosclerosis

When the myeloperoxidase-catalyzed peroxidation of acetoacetate proceeds in the presence of piperidinooxy free radical, methyl glyoxal is formed, and the nitroxide group is reduced to the secondary amine. A mechanism is advanced wherein an alpha-carbon-centered acetoacetate radical, generated by the peroxidase, forms an unstable adduct with the nitroxide group, subsequently decomposing to the observed products. Formation of methyl glyoxal, detected as its bis-2,4-dinitrophenylhydrazone by radial thin-layer chromatography, represents a method of determining free radical acetoacetate peroxidation by other peroxidases. It is shown that lactoperoxidase, prostaglandin synthetase, and prostacyclin synthetase generate methyl glyoxal with requirements identical to those of myeloperoxidase. With prostaglandin synthetase, arachidonic acid could replace the supporting peroxide. Substantiation that the catalyst for the reaction in aortic microsomes was prostacyclin synthetase was obtained by showing that 15-hydroperoxyarachidonic acid strongly inhibited the activity (5). The finding that these peroxidases catalyze radical acetoacetate oxidation could have broad implications for cellular damage via lipid peroxidation (7). Specifically, radical oxidation of acetoacetate by prostacyclin synthetase is proposed to be a link between cardiovascular risk factors and the initiation of atherosclerosis.     

Age-associated changes in rat plasma lipids, platelet fatty acids and prostacyclin release

The effect of age on plasma lipids, platelet fatty acids and prostacyclin release was studied in the rat. The contents of arachidonic acid, cholesterol, bile acids and free fatty acids in the plasma of aged rats (15 months old) were higher than those of young rats (3 months old). No significant differences in fatty acid composition of platelet lipids and release of prostacyclin from aortas between young and aged rats were observed. The data suggest that plasma lipids may play a more important role in the development of cardiovascular disease with increasing age than prostaglandins do.     

The effects of La(III) on the peroxidation of membrane lipids in wheat seedling leaves under osmotic stress

The physiological effects of the rare earth ion La³⁺ on the peroxidation of membrane lipids in wheat (Triticum aestivum L.) seedling leaves under osmotic stress were determined. With the passage of time under osmotic stress, the inhibition ability of lanthanum ions to the relative membrane permeability and concentration of malondialdehyde, Superoxide radicals, and hydrogen peroxide caused by osmotic stress increased substantially, but no changes were noted in ferrous and relative water content. It indicated that lanthanum ions could not retain the water content because of osmotic stress. However, La³⁺ appears to decrease the production of OH by reducing the content of O₂ and H₂O₂ of Haber-Weiss and Fenton reactions, which efficiently alleviated peroxidation of membrane lipids under osmotic stress and, to some degree, protected the membrane from injury of free radicals. Thus, La³⁺ increased the tolerance ability of plant to osmotic stress, which could assure the function of membrane normal temporally after stressed.     

Effects of cystamine and cysteamine on the peroxidation of lipids and the release of proteins from mitochondria

1. Cystamine slightly stimulated the peroxidation of lipids in mitochondria. Maximal effects were obtained at low concentrations (0.5mm). 2. Cysteamine, when allowed to autoxidize, had much stronger effects than cystamine. 3. Cysteamine and GSH did not induce peroxidation when their autoxidation was counteracted. 4. When kept reduced, cysteamine prevented the ascorbate-induced peroxidation of lipids. GSH was less efficient. 5. Cystamine as well as cysteamine prevented the loss of proteins from mitochondria induced by ascorbate, whereas cadaverine, GSSG and GSH were inefficient.     

The effect of cyclooxygenase inhibition on the indices of the thrombocyte-vascular link in hemostasis and on the free-radical processes of lipid oxidation in experimental Salmonella intoxication]

Injection of Salmonella typhimurium endotoxin to the laboratory animals (rabbits) in dose of 1 mg/ml (LD84) induces the particular changes in the thrombocyte vessels system of hemostasis: decrease of aggregatory ability of thrombocytes, increase of thromboxane A2 and prostacyclin activation of lipid peroxidation process. Use of indomethacin--the cyclooxygenase inhibitor--leads to less progressive alterations of the studied parameters of the thrombocyte vessels hemostasis and lipid peroxidation processes.     

Interaction between prostacyclin and colchicine on the gastric mucosa of rat in different experimental ulcer models

The effect of prostacyclin and colchicine on the fundic gastric mucosa of adult female Wistar rats was investigated in stress (immobilization) and indomethacin induced ulcer models. Under prostacyclin treatment the ulcer index decreased significantly in both ulcer models. This effect was inhibited by colchicine. The nuclear volume of fundic epithelial cells increased significantly after application of either type of ulcerogenic stimulus. Prostacyclin did not influence the nuclear volume changes in stress ulcer, while it prevented this phenomenon in indomethacin-induced ulceration. Following colchicine treatment the nuclear volume decreased in both ulcer models. After combined prostacyclin and colchicine treatment the nuclear shrinkage remained unaltered in stress ulcer, while in indomethacin ulcer the nuclear volume decreasing effect of the separately administered drugs disappeared after combined treatment. The latter phenomenon was interpreted as an antagonistic interaction between prostacyclin and colchicine.     

Relative efficacies of indole antioxidants in reducing autoxidation and iron-induced lipid peroxidation in hamster testes

Increased iron stores are associated with free radical generation and carcinogenesis. Lipid peroxidation is involved in DNA damage, thus indirectly participating in the early steps of tumor initiation. Melatonin and structurally related indoles are effective in protecting against oxidative stress. The aim of the study was to compare the relative efficacies of melatonin, N-acetylserotonin (NAS), indole-3-propionic acid (IPA), and 5-hydroxy-indole-3-acetic acid (5HIAA) in altering basal and iron-induced lipid peroxidation in homogenates of hamster testes. To determine the effect of the indoles on the autoxidation of lipids, homogenates were incubated in the presence of each agent in concentrations of 0.0, 0.01, 0.05, 0.1, 0.25, 0.5, 0.75, 1.0, 2.0, 2.5, or 5.0 mM. To study their effects on induced lipid peroxidation, homogenates were incubated with FeSO(4) (30 microM + H(2)O(2) (0.1 mM) + each of the indoles in the same concentrations as above. The degree of lipid peroxidation was expressed as concentrations of malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) per mg protein. The indoles decreased both basal and iron-related lipid peroxidation in a concentration-dependent manner. Melatonin reduced basal MDA + 4-HDA levels when used at the concentrations of 0.25 mM or higher, and prevented iron-induced lipid peroxidation at concentrations of 1.0, 2.0, 2.5, or 5.0 mM. The lowest effective concentrations of NAS required to lower basal and iron-related lipid peroxidation were 0.05 mM and 0.25 mM, respectively. IPA, only when used in the highest concentrations of 2.5 mM or 5 mM inhibited basal lipid peroxidation levels and it was ineffective on the levels of MDA + 4-HDA due to iron damage. 5HIAA reduced basal lipid peroxidation when used at concentrations of 0.25 mM or higher, and it prevented iron-induced lipid peroxidation only at the highest applied concentration (5 mM). In conclusion, melatonin and related indoles at pharmacological concentrations protect against both the autoxidation of lipids as well as induced peroxidation of lipids in testes. In doing so, these agents would be expected to reduce testicular cancer that is initiated by products of lipid peroxidation.     

四种中草药抗白内障形成中晶状体脂类过氧化水平及脂类含量的变化

我们观察了中草药防治大鼠半乳糖性白内障形成中脂类含量的变化及脂类过氧化水平。结果表明,与正常晶状体相比,白内障晶状体中总脂类的含量明显降低,总胆固醇的含量及脂类过氧化水平明显升高,总脂类与总胆固醇之比明显下降。而同时分别用黄苓、石斛、菟丝子及玉蝴蝶四种中草药水煎剂灌胃的大鼠晶状体中,总胆类与总胆固醇的含量基本恢复至正常;脂类过氧化水平虽仍高于正常晶状体,但也明显低于白内障晶状体,表明脂类过氧化参与了白内障的形成,上述四种中草药具有抑制脂类过氧化的作用。     

HDL-induced cardiac prostacyclin synthesis: relative contribution of HDL apoprotein and lipid

The objective of this study was to determine if the apoprotein or lipid constituents of high density lipoproteins (HDL) mediate HDL-induced prostacyclin synthesis in the Langendorff-perfused rabbit heart. Acetylation, acetoacetylation, or partial removal by trypsin digestion of HDL apoprotein did not reduce the ability of the lipoprotein to stimulate cardiac prostacyclin synthesis. Delipidated apoproteins were less effective in stimulating cardiac prostacyclin synthesis in comparison to intact HDL. In contrast, protein-free lipid vesicles, made from HDL lipids, caused a pronounced stimulation of cardiac prostacyclin synthesis. These results suggest that HDL apoproteins, in their native state, are not essential for HDL-induced cardiac prostacyclin synthesis. The stimulation of cardiac prostacyclin synthesis by HDL may depend on the lipoprotein's lipid rather than on its apoprotein constituents.