Possible Involvement Of Lipid Peroxidation Research Articles

Age-related changes of the human retinal vessels: Possible involvement of lipid peroxidation

BackgroundAging of the human retina is accompanied by oxidative stress that exerts profound changes in the retinal neurons. It is unknown if oxidative stress influences the cellular components of the retinal vessels in some ways. MethodsWe examined changes in retinal vessels in human donor eyes (age: 35–94 years; N=18) by light and transmission electron microscopy, TUNEL and immunohistochemistry for biomarkers of vascular smooth muscle cells (SMC; actin), oxidative stress (4-hydroxy 2-nonenal [HNE] and nitrotyrosine), microglia (Iba-1) and vessels (isolectin B4). ResultsThe earliest changes in the endothelium and pericytes of capillaries are apparent from the seventh decade. With aging, there is clear loss of organelles and cytoplasmic filaments, and a progressive thickening of the endothelial and pericyte basal lamina. Loss of filaments, accumulation of lipofuscin and autophagic vacuoles are significant events in aging pericytes and SMC. Actin immunolabelling reveals discontinuity in arterial SMC layers during eighth decade, indicating partial degeneration of SMC. This is followed by hyalinization, with degeneration of the endothelium and SMC in arteries and arterioles of the nerve fibre layer (NFL) and ganglion cell layer in ninth decade. Iba-1 positive microglia were in close contact with the damaged vessels in inner retina, and their cytoplasm was rich in lysosomes. HNE immunoreactivity, but not of nitrotyrosine, was detected in aged vessels from seventh decade onwards, suggesting that lipid peroxidation is a major problem of aged vessels. However, TUNEL positivity seen during this period was limited to few arteries and venules of NFL. ConclusionThis study shows prominent age-related alterations of the pericytes and SMC of retinal vessels. These changes may limit the energy supply to the neurons and be responsible for age-related loss of neurons of the inner retina.

Amelorative effects of anethum graveolens (Dill) against lornoxicam toxicity in rats

Lornoxicam (LOR) is a non-steroidal anti-inflammatory drug known to induce hepato-renal toxicity. The following study aimed to investigate the adverse effect of LOR in oxidative status beside biochemical and histological examination of Liver and kidney tissue as well as the protective effect ofDill. Thirty six male Wister albino rats were randomly divided into main four groups of nine rats each were used; G(1)Control group and they were administered 0.5ml of saline orally for 21 consecutive days, G (2):they were administered 2g/kg dill orally for 21consecutive days, G (3): they were administered 1.3 mg/kg body weight/day of LORintraperitonially for 21 consecutive days, G (4): they were administered 2g/kg dill orally concurrently with 1.3 mg/kg body weight/day of LOR. The results revealed that LOR induced significant increases in liver and kidney function parameters including AST, ALT, creatinine, and urea. Disrupted lipid metabolism also was observed in LOR-treated animals. Moreover, marked an increase in malondialdehyde (MDA) and decreases in glutathione (GSH) and catalase (CAT) following LOR-insult suggested a possible involvement of lipid peroxidation in LOR-induced hepatorenal toxicity.Oral administration of dill at the dose 2g/kg for 21 days was significantly mitigating these toxic effects.So it is concluded that dill has great hepatorenal, antioxidant and antiopoptotic effect.

Rosuvastatin attenuates piroxicam-mediated gastric ulceration and hepato-renal toxicity in rats

Piroxicam (Px) is a non-steroidal anti-inflammatory drug that is widely prescribed in various inflammatory disorders. However, Px is known to induce gastric ulceration and hepato-renal toxicity. Rosuvastatin (ROSV), a member of the statin family, has anti-inflammatory and antioxidant actions independent of its anti-hyperlipidemic action. Therefore, we investigated the protective effects of ROSV against Px-induced gastric, liver, and kidney injury. Five groups of seven rats each were used; control group, ROSV group (20 mg/kg, given orally), Px group (7 mg/kg, given intraperitoneally), Px+ROSV L (7 and 10 mg/kg, respectively), and Px+ROSV H (7 and 20 mg/kg, respectively) group. The results revealed that Px induced severe gastric mucosal damage expressed by high ulcer index along with significant increases in liver and kidney function parameters including AST, ALT, creatinine, and urea. Disrupted lipid metabolism also was observed in Px-treated animals. Moreover, marked an increase in malondialdehyde (MDA) and decreases in glutathione (GSH) and catalase (CAT) levels along with enhanced activated caspase-3 expression in the gastric, hepatic, and renal tissues following Px-insult suggested a possible involvement of lipid peroxidation in Px-induced gastropathy and hepatorenal toxicity. However, in a dose-dependent manner, ROSV was able to mitigate Px-induced lipid peroxidation and apoptosis in gastric, liver, and kidney tissues.

Gastroprotective activities of Turnera diffusa Willd. ex Schult. revisited: Role of arbutin

Ethnopharmacological relevanceTurnera diffusa Willd. ex Schult. has been used for the treatment of several human disorders including peptic ulcer. Objectives of the studyThe current study is an attempt to evaluate the anti-ulcerogenic activities of arbutin, a major constituent of Turnera diffusa on two ulcer models. The possible involvement of lipid peroxidation, nitric oxide, IL-6, IL-10, TNF-α and mucus barrier mechanism has been investigated. Materials and methodsEffects of arbutin on ulcer index, gastric juice acidity, mucus content and histochemistry, gross and histological gastric lesions, nitric oxide, cytokines levels (IL-6, IL-10 and TNF-α), and thiobarbituric acid reactive substances (TBARS), were evaluated in aspirin or ethanol-induced ulcer in vivo. Acute toxicity of arbutin was also examined in rodent model. MTT assay was used to assess the cytotoxicity of the compound on normal liver cells (WRL-68). ResultsPre-treatment with arbutin or omeprazole protected the gastric mucosa as seen by reduction in ulcer area and mucosal content, reduced or absence of edema, inflammation and leucocytes infiltration on both models. Arbutin significantly (P<0.05) lowered the elevated TBARS level into gasteric homogenate. Arbutin did not produce significant inhibition of NO. This natural compound has modulated the levels of interleukin-6, interleukin-10 and TNF-α. No in vitro or in vivo toxicities for arbutin were observed. ConclusionThus it can be concluded that Turnera diffusa possesses anti-ulcer activity, which could be attributed to lipid peroxidation inhibitory, immuno modulatory and anti-oxidant mechanisms of arbutin but not to the intervention with nitric oxide inflammation pathway.

Ferrylmyoglobin impairs secretion of VLDL triacylglycerols from stored intracellular pools: Involvement of lipid peroxidation

Ferrylmyoglobin (ferrylMb) may play a major role in vivo under certain pathological conditions. Preliminary experiments showed that ferrylmyoglobin induced a mild oxidative stress in rat hepatocytes, mainly reflected by early lipid peroxidation. One of the major functions of hepatocytes is the synthesis, secretion and distribution of lipids to other cells. The aim of this work was to examine whether ferrylMb affected the synthesis and secretion of triacylglycerols (TAG), and the possible involvement of lipid peroxidation on these effects. The heme protein completely impaired VLDL secretion, affecting both the lipid and apoB components of the lipoprotein particle. The incorporation of [ 3H]-oleate into newly synthesized diacylglycerol and TAG was not altered by ferrylMb. The co-treatment of cells with α-tocopherol prevented lipid peroxidation and concomitantly reverted VLDL TAG secretion to control values. Importantly, although ferrylMb dramatically blocked prelabeled TAG secretion, newly synthesized TAG secretion was not impaired. These data indicate that lipid peroxidation elicited by ferrylMb modulates the VLDL TAG secretion process, specifically affecting the stored intracellular TAG mobilization, rather than de novo synthesis. Apart from its potential role in vivo, ferrylmyoglobin constitutes a useful model for studying the interactions between lipid peroxidation and the specific TAG pool dependence for VLDL secretion.

Gugulu ( Commiphora mukul) induces triiodothyronine production: Possible involvement of lipid peroxidation

An investigation was made to find out the importance of gugulu ( Commiphora mukul) in thyroid function of mice and to reveal the possible involvement of lipid peroxidation (LPO), if any. While no marked change in the concentrations of serum thyroxine (T 4) was observed, triiodoth yronine (T 3) concentration and T 3 T 4 ratio were enhanced following the administration of gugulu extract (0.2 g kg b. wt. /d for 15 days). A concomitant decrease in LPO was also noticed in liver, the principal site of T 3 generation, suggesting that gugulu induced increase in T 3 concentration is LPO mediated.

Possible involvement of lipid peroxidation in the inhibition of type I iodothyronine 5'-monodeiodinase activity by lead in chicken liver.

The possible involvement of lipid peroxidation (LPO) in the lead-induced inhibition of type I iodothyronine 5'-monodeiodinase activity (5'-D) has been worked out in chicken liver. Lead nitrate (1.5 mg per bird per day) for 30 days increased the lipid peroxidative process with a concomitant decrease in 5'-D activity in chicken liver. Also, a significant decrease in serum triiodothyronine (T3) concentration and an increase in serum thyroxine (T4) concentration were observed. The data suggest that lead-induced inhibition of type I 5'-D activity in chicken liver is mediated through the lipid peroxidative process.

Possible involvement of lipid peroxidation in salicylic acid-mediated induction of PR-1 gene expression

Salicylic acid (SA) is a natural signal molecule which plays an important role in plant defense responses against pathogen infection. Previous work has demonstrated that catalase may be involved in the mechanism of SA action. Recently, SA has been shown to inhibit catalase by serving as a one electron-donating substrate for its peroxidative reaction. One of the likely by-products of this interaction is a SA free radical. Since free radicals are potent inducers of lipid peroxidation, SA and its analogues were tested for their ability to induce lipid peroxidation in tobacco cell cultures. SA and its biologically active analogues, which increase PR gene expression, enhance disease resistance and also inhibit catalase, induced accumulation of lipid peroxidation products. Inactive analogues did not. Exogenous application of lipid peroxides induced PR-1 gene expression. Furthermore, the induction of PR-1 genes by SA was inhibited by diethyldithiocarbamic acid, a compound that converts lipid peroxides into their hydroxyl derivatives. We suggest that the induction of lipid peroxidation by a SA radical may be involved in the action of SA and that one or more of the lipid peroxidation products may mediate signal transduction leading to PR-1 expression.

Selective Cytotoxicity of Piperine on Cultured Rat Hippocampal Neurons in Comparison with Cultured Astrocytes: The Possible Involvement of Lipid Peroxidation.

The present study investigated the selective cytotoxicity of piperine on cultured brain cells by using lactate dehydrogenase release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium reduction, and protein content assay. Exposure to piperine induced marked injuries on cultured hippocampal neurons whereas it induced only a marginal toxicity on cultured astrocytes. The mechanism of cytotoxicity in hippocampal neurons was studied by pharmacological methods. The membrane-permeable free radical scavengers, D-alpha-tocopherol and trolox, protected neurons from piperine toxicity whereas membrane-impermeable agents, superoxide dismutase and catalase, were ineffective. A lipoxygenase inhibitor, nordihydroguaiaretic acid, but not a cyclo-oxygenase inhibitor, indomethacin, attenuated piperine toxicity. We provide the first evidence that piperine induces selective neurotoxicity in vitro. Although the exact mechanism is still unclear, pharmacological evidence indicates the possible involvement of lipid peroxidation and the generation of free radicals, at least partly, through an arachidonate-lipoxygenase pathway.

Free radical mediated membrane perturbation and inhibition of type-I iodothyronine 5'-monodeiodinase activity by lead and cadmium in rat liver homogenate.

The possible involvement of lipid peroxidation (LPO) in the lead (Pb) and cadmium (Cd) induced thyroid dysfunction with special reference to type-I iodothyronine 5'-monodeiodinase (5'-D) activity was studied in rat liver homogenate. Peroxidative reactions involving membrane components were found to be markedly stimulated by chronic administration of Pb and Cd in rats. Metal induced inhibition in 5'-D activity was also observed. Since LPO is primarily an outcome of free radical generation, we suggest metal induced free radical mediated inhibition of 5'-D activity in rat liver homogenate. In addition, serum triiodothyronine (T3) and thyroxine (T4) concentrations were also decreased by metals.

Loss of Membrane Integrity and Inhibition of Type-I Iodothyronine 5′-Monodeiodinase Activity by Fenvalerate in Female Mouse

The possible involvement of lipid peroxidation (LPO) in the fenvalerate-induced thyroid dysfunction with special reference to type I 5′-monodeiodinase (5′-D) activity has been worked out. Fenvalerate (40, 80 and 120 mg/kg body weight) enhanced LPO in biomembranes of liver and kidney leading to a decrease in membrane integrity. 5′-D activity and serum concentration of triiodothyronine (T 3) were reduced by the highest dose. Serum thyroxine (T 4) concentration was decreased in all the three fenvalerate-treated groups, indicating the sensitivity of thyroid gland to this pesticide. A marginal increase in T 4 concentration in highest dose-treated group compared to that of the lower one supports the view that the monodeiodination of the phenolic ring of T 4 is inhibited by fenvalerate. We suggest the possible inactivation of 5′-D by the generated free radicals in pesticide-treated animals.

Interaction of liposomes with cultured cells: Possible involvement of lipid peroxidation in cell growth inhibition.

Systematic analyses of the interaction between liposomes and cells were examined. Liposomes were found to affect the growth of mouse NIH 3T3 cells depending upon their size, net charge, and cholesterol content. Among the charged compounds, stearylamine was the most inhibitory and showed complete inhibition of cell growth at 100 microM. The cholesterol-rich and small unilamellar vesicles were more suppressive compared to the cholesterol-poor and multilamellar ones, respectively. The binding assay of liposomes to the cells showed a positive correlation between liposome binding and the extent of growth inhibition. Suppression of liposome uptake by inhibitors of the cytoskeletal system and energy metabolism were suggestive of an endocytotic mechanism for the cellular uptake of liposomes. The growth inhibitory effect seemed secondary to the intracellular uptake of liposomes, and peroxidation of incorporated lipids would lead to cellular damage. Therefore, it is highly recommended that potential growth inhibitory effects associated with the particular composition and other properties of liposomes should be carefully assessed in any human studies, especially for long-term use.

Plasma lipid peroxides among workers exposed to silica or asbestos dusts

Plasma malondialdehyde (MDA) (an indicator of lipid peroxidation) was determined in random samples of workers (age range 25-60 years) exposed to silica dust (n = 31, mean exposure duration 21.3 +/- 8.3 years) or asbestos dust (n = 59, mean exposure duration 15.6 +/- 4.5 years) and in 52 age-matched healthy male controls. MDA levels of both exposed groups were significantly higher than that of the controls and were significantly higher among workers exposed to asbestos than among those exposed to silica dusts. Neither age nor smoking was related to MDA levels among both controls and exposed workers; among the latter group MDA was not significantly correlated with duration of exposure. Mean MDA levels of exposed workers with radiographic signs of lung fibrosis or pleural thickening and of those without such signs were not significantly different, except in the case of asbestos-exposed workers where it was significantly less than that of those without such signs. Differences between mean durations of dust exposure of workers with radiographic signs of lung fibrosis and those without such signs were statistically insignificant. The results suggest the possible involvement of lipid peroxidation on exposure to silica or asbestos dusts in humans and possible development of antioxidant mechanism(s) on prolonged dust exposure and support the opinion that development of pneumoconiosis depends on susceptibility factor(s).

Effect of visual cortical stimulation on lipid peroxidation in the rabbit retina

Chronic experiments on rabbits have shown that visual cortex stimulation resulted in intensified lipid peroxidation in the retina with the parallel decrease of electroretinogram amplitude parameters. The transsection of the optic nerve resulting in the elimination of retinal corticofugal inputs diminished the accumulation of lipid peroxidation products in the rabbit retina during light adaptation. Preliminary insertion of antioxidants to animals (vitamin E and ionol) prevents the inhibitory effect of the cortex on the function of the retina. The data obtained are discussed in view of possible involvement of lipid peroxidation in the retina into the realization of the regulating influence of the cortex on the function of the retina.

Lipid peroxidation in alcoholic liver disease in humans.

The lipoperoxide level in liver as well as serum in alcoholic patients was measured by using the thiobarbituric acid method. Heavy drinkers with deposition of fat in liver had a significantly (p less than 0.001) higher level of hepatic lipoperoxide examined in about 7 days after abstinence than did nonalcoholic individuals with histologically normal liver. Of these heavy drinkers, cases with a remarkably high level of liver lipoperoxide showed a high incidence of hepatic cell necrosis. The hepatic lipoperoxide level was correlated with the serum lipoperoxide level in these heavy drinkers (r = 0.750, p less than 0.001). In chronic alcoholics, high levels of serum lipoperoxide were usually observed on admission, and a significant positive correlation was found between the serum lipoperoxide level and serum GOT activity (r = 0.541, p less than 0.01). After a 2-wk abstinence, the levels of serum lipoperoxide decreased, which was associated with improvement of liver function tests. These results suggest a possible involvement of lipid peroxidation in alcohol-induced liver damage in humans.

Dissociation between prostagland in and malondialdehyde formation in exudate and increased levels of malondialdehyde in plasma and liver during granulomatous inflammation in the rat

During kaolin-induced granuloma pouch inflammation in the rat the concentration of malondialdehyde (MDA) in the exudate, measured by the 2-thiobarbiturate method, steadily increased and this increase was correlated with the increase in granuloma weight. There was a complete lack of correlation between the concentrations of MDA and prostaglandin (PG)-like material in the inflammatory exudate. Whereas the concentration of PGs reached a maximum 1 day after the induction of inflammation and returned to control levels on day 4, the MDA concentration continuously increased from the initiation of inflammation up to day 16. During granuloma development the concentration of MDA in the plasma reached a maximum on day 2 in parallel with the concentration in the liver, then both plasma and liver MDA decreased to levels observed in control rats. Between day 2 and 8 of the inflammatory process homogenates of livers from inflamed rats showed an increased formation of MDA on incubation, the amount formed being maximal on day 4. The results of the present study are discussed in view of a possible involvement of lipid peroxidation in inflammation.