The relationship between lipid peroxidation and life span in Drosophila melanogaster

Using Drosophila lines pre-selected for adaptive characters, studies have been made on the relationship between the intensity of lipid peroxidation and life span in flies of different genotype, age and physiological condition. It was shown that the intensity of lipid peroxidation depends mainly on different factors (sex, age, virginity) in different lines. No expected negative correlation was found between the level of lipid peroxidation and life span in hybrids between two inbred lines. The intensity of lipid peroxidation was inherited like a dominant character, the dynamics of aging--like a codominant one in females and superdominant in males. Both the level of lipid peroxidation and life span appeared to be sex-dependent characters.     

A comparative genetic analysis of interlinear differences in intensity of lipid peroxidation and life span in Drosophila melanogaster. Inbred lines and hybrids

The interrelationship between the level of peroxidation lipid and longevity was studied as based on highly inbred lines of Drosophila melanogaster, bred for adaptively important characters. The concepts of the free-radical theory proved valid for the lines and failed to be supported for the crosses. The dominant role of heterosis in the protecting against the "aging action" of free radicals is postulated.     

Phenomenon of life span instability in Drosophila melanogaster: I. Nonrandom origin of life span variations in successive generations

The dynamics of life span (LS) and fecundity in Drosophila melanogaster, strain D-32, were analyzed in a series of successive generations. Highly reliable variations in both fitness components were found. On initial inspection the variations would be characterized as random or irregular wherein mean values differed up to threefold. The variance in longevity is greater in females than in males. By use of mathematical procedures we have shown a scale regularity in LS distributions for all generations. Such regularity, in spite of considerable differences in absolute values (mean and maximum LS), suggested that the origin of LS instability is nonrandom.     

Effects of melatonin on lipid peroxidation induced by oxygen radicals

Osteoporosis is characterized by reduced bone mass and a deterioration of bone structure which results in an increased fracture risk. The purpose of this review is to evaluate structure analysis techniques in the diagnosis of osteoporosis. Several imaging techniques were applied to analyze trabecular bone, such as conventional radiography, high-resolution computed tomography (HR-CT) and high-resolution magnetic resonance imaging (HR-MRI). The best results were obtained using high-resolution tomographic techniques. The highest spatial resolutions in vivo were achieved using HR-MRI. These studies show that texture parameters and bone mineral density predict bone strength and osteoporotic fractures in a complementary fashion. Combining both techniques yields the best results in the diagnosis of osteoporosis.     

Influence of photosensitizers and light on the life span of Drosophila

The life span of adult Drosophila melanogaster fruit flies changed when they were fed two different photosensitizers. Methylene blue decreased the median life span by 49% when present in the food at a concentration of 0.001 M. Another photosensitizer, riboflavin, produced no changes in life span under the same conditions of a 12:12 h light/dark cycle at a daytime light intensity of 1000 lux. Flies exposed to constant darkness lived 43.2% longer than those exposed to constant light at a light intensity of 2000 lux. Under these conditions, riboflavin increased the life span of the flies exposed to constant light by as much as 25%. We conclude that riboflavin confers some degree of protection against the effects of constant light exposure. The completely different results obtained with riboflavin and methylene blue suggest a possible mechanism for photoageing involving photodynamic action mediated through the production of singlet oxygen.     

FLP recombinase-mediated induction of Cu/Zn-superoxide dismutase transgene expression can extend the life span of adult Drosophila melanogaster flies

Yeast FLP recombinase was used in a binary transgenic system ("FLP-OUT") to allow induced overexpression of catalase and/or Cu/Zn-superoxide dismutase (Cu/ZnSOD) in adult Drosophila melanogaster. Expression of FLP recombinase was driven by the heat-inducible hsp70 promoter. Once expressed, FLP catalyzed the rearrangement and activation of a target construct in which expression of catalase or Cu/ZnSOD cDNAs was driven by the constitutive actin5C promoter. In this way a brief heat pulse (120 or 180 min, total) of young adult flies activated transgene expression for the rest of the life span. FLP-OUT allows the effects of induced transgene expression to be analyzed in control (no heat pulse) and experimental (heat pulse) populations with identical genetic backgrounds. Under the conditions used, the heat pulse itself always had neutral or slightly negative effects on the life span. Catalase overexpression significantly increased resistance to hydrogen peroxide but had neutral or slightly negative effects on the mean life span. Cu/ZnSOD overexpression extended the mean life span up to 48%. Simultaneous overexpression of catalase with Cu/ZnSOD had no added benefit, presumably due to a preexisting excess of catalase. The data suggest that oxidative damage is one rate-limiting factor for the life span of adult Drosophila. Finally, experimental manipulation of the genetic background demonstrated that the life span is affected by epistatic interactions between the transgene and allele(s) at other loci.     

Prolongation of life in an experimental model of aging in Drosophila melanogaster

The mammalian fetus has been perceived, paradoxically, as a successful allograft, a successful tumor, and a successful parasite. Success depends on fetal trophoblast cells, which form the interface with the mother. The maternal immune system is involved in the success of pregnancy and in its failure. The discovery that maternal gammadelta T cells may recognize and react to the fetal trophoblast and the definition of a vascular mechanism whereby their Th1 and Th2/3-type cytokines may abort embryos replaces confusion and debate with a new and simple clarity that enables further research.     

Effect of L-carnitine on lipid peroxidation and lipid composition in blood serum in hemic hypoxia]

Sodium nitrite has been studied for its effect on lipid metabolism of Wistar line rats. It is shown that a single administration of sodium nitrite in account 5 mg per 100 g of the body weight results in the intensification of lipids peroxidation, hyperbetalipoproteinemia, hypertriglyceridemia, hypercholesterolemia and to the decrease of the coefficient phospholipids/cholesterin/. Prophylactic administration of carnitine chloride in account of 20 mg per 100 g of the body weight stabilizes the level of lipids peroxidation, decreases concentration of total lipids, triglycerides, total cholesterin, phospholipids, lipoproteids of low and very low density, in the rat blood serum, normalizes the coefficient phospholipids/cholesterin.     

Effect of hexachlorocyclohexane on hsp26 expression in transgenic Drosophila melanogaster

The type and amount of lipophilic antioxidants in plasma of hyperlipidemic patients are of great importance since they play a central role in preventing deleterious oxidation of blood lipids and proteins. Isolation and quantitation of lipophilic antioxidants from hyperlipidemic plasma samples meet great obstacles because of increased levels of various intermediary lipid products. This study was designed to develop a rapid and efficient extraction and separation procedure for simultaneous analysis of ubiquinone-9 and -10 as well as alpha-, delta-, and gamma-tocopherol isomers. The levels of ubiquinone-10, alpha- and gamma-tocopherol were analyzed in human plasma samples using high-performance liquid chromatography. Lipid extraction was performed by petroleum ether/methanol/water. After phase separation, ubiquinone was reduced to ubiquinol by sodium borohydride and the lipids were separated on a C18 column. A binary gradient with solvents containing lithium perchlorate was used, and an electrochemical detector was employed for quantitation. This procedure was also efficient for the analysis of antioxidant lipids in samples containing a large number of accumulated and interfering lipid intermediates. Thus, the procedure described here is useful for efficient and rapid quantitation of ubiquinones and tocopherols in human plasma samples, especially those originating from hyperlipidemic patients.     

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.     

Effect of deoxycholic acid and ursodeoxycholic acid on lipid peroxidation in cultured macrophages

BACKGROUND: Kupffer cells are essential for normal hepatic homeostasis and when stimulated, they secrete reactive oxygen species, nitric oxide, eicosanoids, and cytokines. Some of these products are cytotoxic and attack nucleic acids, thiol proteins, or membrane lipids causing lipid peroxidation. Hydrophobic bile acids, such as deoxycholic acid (DCA), can damage hepatocytes by solubilising membranes and impairing mitochondrial function, as well as increasing the generation of reactive oxygen species. OBJECTIVES: The hypothesis that hydrophobic bile acids could stimulate Kupffer cells to increase their capacity to generate reactive oxygen species by measuring cellular lipid peroxidation was tested. Because the hydrophilic bile acid, ursodeoxycholic acid (UDCA) can block hydrophobic bile acid induced cellular phenomena, it was also hypothesised that UDCA could antagonise macrophage activation by hydrophobic bile acids to blunt their capacity to generate reactive oxygen species. METHODS: J-774A.1 murine macrophages were incubated for 24 hours with either 10(-5) M and 10(-4) M (final concentration) DCA alone, or 10(-4) M UDCA alone, or a mixture of 10(-4) M 1:1 molar ratio of DCA and UDCA. At the end of the incubation period, the culture medium was collected for determination of cellular lipid peroxidation by measuring the malondialdehyde (MDA) content in the medium with the thiobarbituric acid reactive substances assay. RESULTS: 10(-5) M and 10(-4) M DCA increased MDA generation by cultured macrophages. 10(-4) M UDCA alone did not increase MDA generation but blocked the peroxidative actions of DCA. CONCLUSIONS: Hydrophobic bile acids, after their hepatic retention, can oxidatively activate Kupffer cells to generate reactive oxygen species. Because UDCA can block this action, the beneficial effect of UDCA is, in part, related to its ability to act as an antioxidant.     

Effect of alpha-tocopherol on lipid peroxidation and total antioxidant status in spontaneously hypertensive rats

The aim of this study was to determine the effects of alpha-tocopherol on lipid peroxidation and total antioxidant status of spontaneously hypertensive rats (SHR), comparing them with normal Wistar-Kyoto (WKY) rats. SHR were divided into three groups and treated with different doses of alpha-tocopherol (alpha1, 17 mg/kg diet; alpha2, 34 mg/kg diet; and alpha3, 170 mg/kg diet). Normal WKY and untreated SHR were used as normal (N) and hypertensive control (HC). Blood pressures were recorded every 10 days for 3 months. At the end of the trial, animals were killed and measurement of plasma total antioxidant status, plasma superoxide dismutase (SOD) activity, and lipid peroxide levels in plasma and blood vessels was carried out following well-established methods. From our study it was found that lipid peroxides in thoracic aorta (N, 0.47 +/- 0.17; H, 0.96 +/- 0.37; P < .0001) and plasma (N, 0.06 +/- 0.01; H, 0.13 +/- 0.01) were significantly higher in hypertensives than in normal rats. SOD activity was significantly lower in hypertensive than normal rats (N, 172.93 +/- 46.91; H, 110.08 +/- 14.38; P < .005). Total antioxidant status was significantly higher in normal than hypertensive rats (N, 0.88 +/- 0.05; H, 0.83 +/- 0.02; P < .05). After the antioxidant trial, it was found that in the treated groups rise of blood pressure was prevented significantly (P < .001) and lipid peroxides in blood vessels were significantly reduced more than in the controls (P < .001). For plasma lipid peroxide it was only significant for groups alpha2 (P < .001) and alpha3 (P < .05). Although all three treated groups showed improved total antioxidant status, only groups alpha2 (0.87 +/- 0.04, P < .005) and alpha3 (1.20 +/- 0.18, P < .001) were statistically significant. All the three groups showed significant increases in their SOD activity (P < .001). Correlation studies showed that total antioxidant status and SOD were significantly negatively correlated with blood pressure in normal rats (P = .007; P = .008). Lipid peroxides in both blood vessel and plasma showed a positive correlation. In the treated groups, lipid peroxides in blood vessels maintained a significant positive correlation with blood pressure in all groups (alpha1, P = .021; alpha2, P = .019; alpha3, P = .002), whereas for plasma lipid peroxides the correlation was in groups alpha1 (P = .005) and alpha2 (P = .009). For SOD activity, significant negative correlations were found with blood pressure in the alpha2 (P = .017) and alpha3 (P = .025) groups. Total antioxidant status maintained a significant negative correlation with blood pressure in all three groups (alpha1, P = .012; alpha2, P = .044; alpha3, P = .014). In conclusion it was found that supplement of alpha-tocopherol may prevent development of increased blood pressure, reduce lipid peroxides in plasma and blood vessels, and enhance the total antioxidant status, including SOD activity.     

Effect of hyperbaric oxygen on lipid peroxidation in free skin grafts in rats

OBJECTIVE: To document that free skin grafts treated with hyperbaric oxygen (HBO) are at greater risk for reperfusion injury, resulting in lipid peroxidation, than are free skin grafts without HBO treatment. ANIMALS: 40 Sprague-Dawley rats. PROCEDURE: Free skin grafting was performed bilaterally on each rat. The HBO-treated rats received HBO twice daily for 90 minutes at 2 ATA. Biopsy specimens were taken from each rat at the time of grafting and on days 2, 4, 7, 10, 14, 21, and 28, then were processed for tissue concentration of total glutathione (GSHt), glutathione peroxidase activity (GPx), and presence of thiobarbituric acid-reactive substances (TBARS). RESULTS: Both groups had a similar pattern of change in TBARS and GPx values--initial increase, returning to preoperative values at days 21 (control) and 28 (HBO). The GPx activity peaked later than did TBARS concentration (day 7 vs day 4). The pattern was significantly more pronounced in HBO-treated than in control rats. Both groups had a similar pattern of change in GSHt values-significant decrease from preoperative concentration at day 2, return to preoperative concentration by days 4 (HBO) and 7 (control), increase above preoperative concentration by day 21, and return to preoperative concentration by day 28. Obvious visual or histologic differences in the grafts were not detected between groups. CONCLUSIONS: Cellular effects of oxidative stress were apparent in both groups of rats; however, the degree of these effects was exacerbated by HBO. In the face of enhanced cellular lipid peroxidation, use of HBO for the treatment of free skin grafts must be questioned.     

Effect of high glucose on cellular proliferation and lipid peroxidation in cultured Vero cells

Nephropathy is common among the diabetic population. However, the molecular mechanisms by which hyperglycemia can cause alteration in kidney structure and function is not known. In this study, we examined the effect of high glucose levels on cellular growth and membrane lipid peroxidation in Vero cells, an African green monkey kidney cell line. Cell growth was assessed by a tetrazolium salt reduction test (MTT); and lipid peroxidation was measured by thiobarbituric acid reactivity. Our results show that elevated levels of glucose (25, 50 and 100 mM) can cause up to 50% reduction in cell growth in cultured Vero cells as compared with controls (8 mM). Also, we observed a significant increase in the amount of oxidative damage in Vero cells cultured with elevated glucose concentrations. This study demonstrates that hyperglycemia can cause increased lipid peroxidation and affect the cellular proliferation in a monkey kidney cell line.     

Effect of heparin on the lipid peroxidation reaction of erythrocytes and their stability

Physiological concentration (10 units/ml) of heparin activates ascorbate-dependent lipid peroxidation of erythrocytes and reduces their stability in the citrate-phosphate buffer (pH 3.0). In a concentration of 100 units/ml heparin does not influence the thermal (62 degrees) oxidation of methyloleate. It follows that heparin is not direct prooxidant.     

Effect of iron, zinc, and copper on lipid peroxidation in liver in vivo

Changes in the levels of lipid peroxides, natural antioxidants (NA), iron, zinc and copper as well as the ability of the lipid substrate to oxidize in animal liver in the presence of iron, zinc and copper have been studied. It has been found that those metals increase the amplitude of natural fluctuations in iron, zinc and copper levels in the liver (by 5-30% in comparison with control). Within the first few hours following administration of iron and copper, the concentration of lipid peroxidation (LPO) products in animal livers increases, while the NA level and lipid oxidizeability decrease, in contrast. Zinc inhibits LPO in the liver within the first few hours following the injection. The changes in the content of NA, lipid oxidizeability and the level of LPO products in animal livers following iron, zinc and copper administration are phase-dependent. Data from regression analysis indicate a direct dependence (kcor = 0.98 at p < or = 0.05) between lipid oxidizeability and NA content in the liver following administration of iron, zinc and copper which, in turn, is suggestive of the lack of disturbances in the system of NA regulation     

Geographic variations of life history strategies in Drosophila melanogaster. III. New data

A crucial assumption of evolutionary theories of aging is that age-specific differences of life history traits may have genetic causes. The present study focuses on the existence of such differences between eight freshly caught populations of Drosophila melanogaster. A highly significant differentiation of the populations is observed, yet it accounts for a relatively small part of the variance. It is also shown that large discrepancies may be found between the estimations of fitness based, on the one hand, on data for egg production and, on the other hand, on fertility data. This stresses the need for accurate measurements of fitness for the assessment of evolutionary theories. Finally, the results suggest that neither of the current evolutionary theories of aging is generally valid. Indeed, the age-specific differences that are found between the populations match either the antagonistic pleiotropy mechanism, or the concordant pleiotropy mechanism, or none of them.