Effect of Spirulina on Lipid Profile, Glucose and Malondialdehyde Levels in Type 2 Diabetic Patients

Abstract The study aimed to assess possible spirulina effects on lipid profile, glucose, and malondialdehyde levels in new cases of type 2 diabetes. The subjects consisted of 30 new cases of types 2 diabetes that divided into two groups; each consisted of 15 diabetic patients. Group I did not take any functional food or supplement and received no spirulina supplementation. Group II or experimental group also did not take any functional food or supplement but received spirulina supplementation. Analysis of data was done using SPSS 16.0. The Kolmogorov-Smirnov test, paired t-test, Wilcoxon test, and Spearman correlation analysis were used to analyze the data. After eight weeks of spirulina supplementation, significant differences were shown in the serum levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, and malondialdehyde. The serum fasting blood glucose, lipid profiles, and malondialdehyde levels at baseline were negatively and positively correlated with changes in these parameters. Spirulina supplementation may have a beneficial effect on lipid profile and malondialdehyde (MDA) levels through an interventional 8 weeks. This effect may protect subjects against free radicals and the development of some diseases such as atherosclerosis. The spirulina supplementation also showed a potential lipid-lowering effect on new case type 2 diabetic patients which may help the diabetics to have control on lipid levels. In addition, spirulina may be used as a functional food for the management of lipid profiles and MDA levels.

Acute effect of a maximum incremental test until exhaustion on malondialdehyde and antioxidant vitamins in plasma and erythrocytes in athletes / Efecto agudo de un test incremental máximo hasta la extenuación sobre el malondialdehído y las vitaminas antioxidantes en plasma y eritrocitos en atletas

BACKGROUND: it is well known that moderate or vigorous physical exercise produces an increase in free radicals. AIM: the aims of this study were to observe changes in malondialdehyde and antioxidant vitamins after a maximum incremental test, and to relate malondialdehyde and antioxidant vitamin values to performance parameters. METHODS: eighty-four male athletes participated in this study. Participants performed a maximum incremental test until exhaustion on a treadmill. Malondialdehyde in plasma and antioxidant vitamins in plasma and erythrocytes were determined before and after the test. RESULTS: in plasma, there was a decrease in malondialdehyde after the test. In erythrocytes, results showed increases in vitamin C and decreases in vitamin E after the test. Maximal oxygen uptake values were associated positively with vitamin C and negatively with malondialdehyde levels before the test. On the other hand, maximal oxygen uptake, total test time, and total test distance were positively related to the malondialdehyde values obtained after the test. CONCLUSIONS: a maximum incremental test did not produce any changes in plasma vitamins in athletes. However, it increased the levels of vitamin C in erythrocytes and decreased malondialdehyde values in plasma and vitamin E in erythrocytes. The levels of malondialdehyde, vitamin C and vitamin E were related to performance parameters. These results may be linked to the adaptation of antioxidant systems due to regular training

INTRODUCCIÓN: es sabido que el ejercicio físico moderado o vigoroso produce un aumento de radicales libres. OBJETIVOS: los objetivos del estudio fueron: observar los cambios del malondialdehído y las vitaminas antioxidantes después de un test incremental máximo y relacionar los niveles de malondialdehído y vitaminas antioxidantes con parámetros de rendimiento. MÉTODOS: ochenta y cuatro atletas masculinos participaron en el estudio. Los participantes realizaron un test incremental hasta la extenuación en un tapiz rodante. El malondialdehído en plasma y las vitaminas antioxidantes en plasma y en eritrocitos se determinaron antes y después del test incremental. RESULTADOS: en el plasma hubo una disminución del malondialdehído después de la prueba incremental. En los eritrocitos, los resultados mostraron un aumento de la vitamina C y un descenso de la vitamina E después de la prueba. El consumo máximo de oxígeno se asoció positivamente con la vitamina C e inversamente con el malondialdehído antes del test. Por otro lado, el consumo máximo de oxígeno, el tiempo total del test y la distancia total durante el test se asociaron positivamente con los valores de malondialdehído obtenidos tras el test máximo. CONCLUSIÓN: un test incremental máximo hasta la extenuación no produjo cambios en las vitaminas antioxidantes del plasma. Sin embargo, sí aumentó los niveles de vitamina C en los eritrocitos y redujo los niveles de malondialdehído en el plasma y los de vitamina E en los eritrocitos. Los niveles de malondialdehído, vitamina C y vitamina E se relacionaron con los parámetros de rendimiento. Estos resultados podrían estar relacionados con la adaptación de los sistemas antioxidantes debido al entrenamiento regular

NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy.

N-methyl-D-aspartate receptors (NMDAR) play a central role in epileptogensis and NMDAR antagonists have been shown to have antiepileptic effects in animals and humans. Despite significant progress in the development of antiepileptic therapies over the previous 3 decades, a need still exists for novel therapies. We screened an in-house library of small molecules targeting the NMDA receptor. A novel indolyl compound, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, (DDBM) showed the best binding with the NMDA receptor and computational docking data showed that DDBM antagonised the binding sites of the NMDA receptor at lower docking energies compared to other molecules. Using a rat electroconvulsive shock (ECS) model of epilepsy we showed that DDBM decreased seizure duration and improved the histological outcomes. Our data show for the first time that indolyls like DDBM have robust anticonvulsive activity and have the potential to be developed as novel anticonvulsants.

Malondialdehyde induces autophagy dysfunction and VEGF secretion in the retinal pigment epithelium in age-related macular degeneration.

Age-related macular degeneration (AMD) is a major cause of blindness in developed countries and is closely related to oxidative stress, which leads to lipid peroxidation. Malondialdehyde (MDA) is a major byproduct of polyunsaturated fatty acid (PUFA) peroxidation. Increased levels of MDA have been reported in eyes of AMD patients. However, little is known about the direct relationship between MDA and AMD. Here we show the biological importance of MDA in AMD pathogenesis. We first confirmed that MDA levels were significantly increased in eyes of AMD patients. In ARPE-19 cells, a human retinal pigment epithelial cell line, MDA treatment induced vascular endothelial growth factor (VEGF) expression alternation, cell junction disruption, and autophagy dysfunction that was also observed in eyes of AMD patients. The MDA-induced VEGF increase was inhibited by autophagy-lysosomal inhibitors. Intravitreal MDA injection in mice increased laser-induced choroidal neovascularization (laser-CNV) volumes. In a mouse model fed a high-linoleic acid diet for 3 months, we found a significant increase in MDA levels, autophagic activity, and laser-CNV volumes. Our study revealed an important role of MDA, which acts not only as a marker but also as a causative factor of AMD pathogenesis-related autophagy dysfunction. Furthermore, higher dietary intake of linoleic acid promoted CNV progression in mice with increased MDA levels.

Investigation of the effect of intracolonic melatonin gel formulation on acetic acid-induced colitis.

The aims of the present study were to develop a colon-specific gel formulation of melatonin with sodium alginate and to evaluate its in vitro characteristics and intracolonic performance on oxidative stress parameters, such as nitric oxide (NOx), malondialdehyde (MDA) and glutathione (GSH) levels in rats with acetic acid-induced colitis. The melatonin-alginate gel formulations were prepared and their physico-pharmaceutical properties were determined. Formulation M5, which contained 3% of sodium alginate and 20% polyethylene glycol, was used for in vivo studies. The in vivo studies were conducted in rats with acetic acid-induced colitis. NOx, MDA and GSH levels were determined and histological investigations were performed. It was found that formulation M5 was the most suitable formulation for the colon-specific melatonin gel, in terms of pH, viscosity, drug release and mucoadhesion properties. The MDA levels in the tissues of Group 2 (treated with an intracolonic gel formulation without melatonin) were found to be significantly higher than in Group 1 (the untreated group). NOx levels decreased with the intracolonic and systemic melatonin treatment in the colitis-induced rats. Neither intracolonic nor intra-peritoneal (IP) melatonin treatment affected GSH levels. The epitelization of the colon tissues in groups administered with intracolonic melatonin, IP melatonin, and the intracolonic gel formulation without melatonin was much better than that found in the untreated group. It was concluded that melatonin participated in various defense mechanisms against the colonic inflammatory process, and that the dose, route and formulation type were the most important parameters in the effectiveness of melatonin.

Ethanol at low concentration attenuates diabetes induced lung injury in rats model.

To observe the changes of lung injury when diabetic rats were treated with low concentration of ethanol (EtOH) and analyze the related mechanisms, male Sprague-Dawley (SD) rats were divided into control, diabetic (DM), and EtOH+DM groups. Diabetic rat was mimicked by injection of streptozotocin intraperitoneally. Fasting blood glucose (FBG) level, lung weight (LW), body weight (BW), and LW/BW were measured. The changes of lung tissue and Type II alveolar cell were detected. Pulmonary malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured; meanwhile, ALDH2 mRNA and protein expressions were detected by RT-PCR and western blotting, respectively. Compared with control group, in DM group, SOD activity was decreased; FBG level, LW/BW, MDA content, ALDH2 mRNA, and protein expressions were decreased. Compared with DM group, in EtOH+DM group, SOD activity, ALDH2 mRNA, and protein expressions were increased; LW/BW and MDA content were decreased. The structures of lung tissue and lamellar bodies were collapsed in DM group; the injury was attenuated in EtOH+DM group. Our findings suggested that, in diabetic rat, pulmonary ALDH2 expression was decreased accompanying lung injury. EtOH at low concentration decreased diabetes induced lung injury through activating ALDH2 expression.

Immunization of apoE-/- mice with aldehyde-modified fibronectin inhibits the development of atherosclerosis.

AIMS: Oxidation of low-density lipoprotein in the extracellular matrix of the arterial wall results in the formation of malondialdehyde (MDA) that modifies surrounding matrix proteins. This is associated with the activation of an immune response against modified extracellular matrix proteins present in atherosclerotic plaques. Clinical studies have revealed an inverse association between antibodies to MDA-modified fibronectin and risk for development of cardiovascular events. To determine the functional role of these immune responses in atherosclerosis, we performed studies in which apoE-deficient mice were immunized with MDA-modified fibronectin. METHODS AND RESULTS: Immunization of apoE-deficient mice with MDA-modified fibronectin resulted in a 70% decrease in plaque area and a less inflammatory phenotype of remaining plaques. Immunization shifted a weak naturally occurring Th1 antibody response against MDA-fibronectin into a Th2 antibody response. Cytokine expression and flow cytometry analyses of spleen cells from immunized mice showed an activation of regulatory T cells. Immunization with MDA-fibronectin was also found to reduce plasma fibronectin levels. CONCLUSION: Immunization with MDA-fibronectin significantly reduces the development of atherosclerosis in apoE-deficient mice suggesting that the immune response observed in humans may have a protective effect. MDA-fibronectin represents a possible novel target for immunomodulatory therapy in atherosclerosis.

Avaliação dos níveis de peroxidação lipídica em células da mucosa cólica após aplicação de enemas com peróxido de hidrogênio: estudo experimental em ratos / Evaluation of lipid peroxidation levels on mucosa colonic cells afther application of hydrogen peroxide in enemas: experimental study in rats

A aplicação de clisteres contendo peróxido de hidrogênio (H2O2) determina o aparecimento de quadros graves de colite, algumas vezes de evolução fatal. É possível que a colite induzida por H2O2 possa ocorrer pela quebra da barreira funcional do epitélio cólico por estresse oxidativo. Objetivo: Avaliar os níveis de peroxidação lipídica em células da mucosa cólica após instilação de H2O2 no reto excluso de trânsito fecal. Método: Vinte seis ratos Wistar machos foram submetidos a colostomia proximal terminal no cólon descendente e fístula mucosa distal. Os animais foram randomizados em dois grupos segundo o sacrifício ter sido realizado duas ou quatro semanas após a derivação intestinal. Cada grupo experimental foi dividido e dois subgrupos segundo aplicação de clisteres, em dias alternados, contendo solução fisiológica a 0,9 por cento ou H2O2 a 3 por cento. O diagnóstico de colite foi estabelecido por estudo histopatológico e os níveis de dano oxidativo tecidual pela dosagem de malondialdeído por espectrofotometria. Os resultados foram analisados com os testes de Mann-Whitney e Kruskal-Wallis, estabelecendo-se nível de significância de 5 por cento (p menor que0,05)

Resultados: Os níveis de malondialdeído nos irrigados com SF nos cólons com e sem trânsito fecal após duas e quatro semanas de irrigação foram de: 0,05 mais ou menos 0,006; 0,06 mais ou menos 0,006 e 0,05 mais ou menos 0,03, 0,08 mais ou menos 0,02, respectivamente. Os níveis de malondialdeído nos irrigados com H2O2, nos cólons com e sem trânsito, após duas e quatro semanas de irrigação foram de 0,070 mais ou menos 0,006; 0,077 mais ou menos 0,01 e 0,052 mais ou menos 0,01, 0,08 mais ou menos 0,04, respectivamente. Após duas semanas os níveis de malondialdeído foram maiores nos animais irrigados com H2O2 em relação ao grupo controle (p= 0,007 e p= 0,01, respectivamente). Após quatro semanas não houve diferenças significantes Não ocorreu variação nos níveis de malondialdeído com o decorrer tempo de irrigação. Conclusão: Clisteres com H2O2, podem determinar o aparecimento de colite por ocasionarem estresse oxidativo nas células epiteliais da mucosa intestinal.

The use of rectal enemas with hydrogen peroxide (H2O2) determines the onset of severe colitis, sometimes with fatal evolution. It is possible that H2O2-induced colitis can occur by damage to the functional epithelial barrier of the colon by oxidative stress. Objective: The aim of present study was evaluate the levels of lipid peroxidation in cells of the colonic mucosa after instillation of H2O2 into the rectum excluded from fecal transit. Method: Twenty six male Wistar rats were undergone to proximal terminal colostomy in the descending colon and distal mucous fistula. The animals were randomized in two experimental groups according to the sacrifice was made two or four weeks after diversion of the fecal stream. Each experimental group was divided into two subgroups second application of enemas containing saline solution 0.9 percent or 3 percent H2O2 on alternate days. The diagnosis of colitis was established by histopathology study and the oxidative damage by tissue levels of malondialdehyde quantified by spectrophotometry. The results were analyzed with the Mann-Whitney and Kruskal-Wallis test, adopting a significance level of 5 percent (p less than 0.05).

Results: The levels of malondialdehyde in colon segments irrigated with saline, with and without fecal stream after two and four weeks of irrigation were: 0.05 more or less 0.006, 0.06 more or less 0.006 and 0.05 more or less 0.03, 0.08 more or less 0.02, respectively. The levels of malondialdehyde in colon segments irrigated with H2O2, in the colon with and without fecal stream, after two and four weeks of irrigation were 0.070 more or less 0.006, 0.077 and 0.052 more or less 0.01 more or less 0.01, 0.08 more or less 0.04, respectively . After two weeks the levels of malondialdehyde were higher on animals irrigated with H2O2 than control group (p = 0.007 and p = 0.01, respectively). After four weeks there were no significant differences in malondialdehyde levels related with the time of irrigation. Conclusion: Rectal enemas with H2O2, may determine the onset of colitis by oxidative stress on epithelial cells of intestinal mucosa.

Vitamin E inadequacy observed in a group of 2- to 6-year-old children living in Kwangju, Republic of Korea.

Studies on the vitamin E status of Korean children are lacking. Dietary intakes and plasma concentrations of tocopherols of healthy 2- to 6-year-olds living in Kwangju, Republic of Korea, were determined and their vitamin E status evaluated. Subjects included 66 girls and 65 boys, with 21-32 subjects per age group. Subjects' intakes were recorded by a trained interviewer for foods eaten at preschool/kindergarten; otherwise, three consecutive 24-hour food recalls were obtained from parents. Plasma tocopherol concentrations were determined using high-performance liquid chromatography. Intakes of energy and total monounsaturated and polyunsaturated fats were significantly different (p < 0.05) among age groups, not gender, with 2- and 3-year-olds having lower intakes. Alpha- and gamma-tocopherol intakes were similar by age and gender. Sixty-seven percent consumed less than the Korean Adequate Intakes for vitamin E, and 77% had Alpha-tocopherol intakes less than USA/Canadian Estimated Average Requirements. Plasma alpha-tocopherol concentrations, but not gamma-tocopherol, were significantly higher (p < 0.05) for 2-year-olds. Two-thirds of subjects had plasma alpha-tocopherol concentrations less than 12 micromol/L, which is indicative of vitamin E inadequacy in adults; guidelines for children do not exist. Many of the Korean children had inadequate intakes and likely inadequate plasma concentrations of vitamin E.

Adduction of soluble proteins with malondialdehyde-acetaldehyde (MAA) induces antibody production and enhances T-cell proliferation.

BACKGROUND: The alcohol metabolites malondialdehyde and acetaldehyde can combine to form stable adducts (MAA) which are found in the livers of humans and rats after significant alcohol ingestion. While adducted proteins induce antibody responses in the absence of adjuvants, the mechanisms by which these responses occur are unknown. Thus, it was the purpose of these studies to investigate how MAA modification stimulates antibody and T-cell responses in the absence of adjuvants. METHODS: Hen egg lysozyme (HEL) was modified with increasing levels of MAA and was used as an immunogen, and antibody and T-cell responses were determined. The role of scavenger receptors in the immunogenicity of MAA-adducted proteins was also investigated. RESULTS: Maximum antibody response was induced after immunization with 1.8 nM MAA/nM HEL, and was primarily an IgG1 response to HEL as determined by inhibition ELISAs. T-cell proliferative responses after immunization with HEL-MAA were solely to HEL. Immunization with a scavenger receptor ligand in conjunction with HEL-MAA increased the predominant IgG1 response and sharply decreased the IgG2a response by approximately 50%. Binding of HEL-MAA by splenocytes was determined by flow cytometry to be approximately 15% greater than HEL alone, showing a doubling of the geometric mean fluorescence. Also, most of the cells that bound HEL-MAA were class II positive, indicating that antigen-presenting cells can bind the MAA-adducted HEL, and potentially initiate immune responses. CONCLUSIONS: MAA modification of proteins induces antibody and T-cell proliferative responses in vivo. Initial studies suggest that these responses may be mediated by scavenger receptors that recognize MAA-adducted proteins. This suggests a mechanism by which proteins modified with oxidative products associated with chronic ethanol consumption may alter immune responses that may play an active role in the development and/or progression of alcoholic liver disease.

Mutagenicity of the malondialdehyde oligomerization products 2-(3'-oxo-1'-propenyl)-malondialdehyde and 2,4-dihydroxymethylene-3-(2,2-dimethoxyethyl)glutaraldehyde in Salmonella.

Malondialdehyde (MDA), a byproduct of non-enzymatic lipid peroxidation and prostaglandin biosynthesis, has been shown to be a weak frameshift mutagen in Salmonella mutagenicity assays. Because it is a dialdehyde, MDA can undergo self condensation to form polymeric products. It is possible that these condensation products are highly mutagenic and have contributed to previously reported estimates of MDA mutagenicity. We synthesized two major MDA polymerization products, (1) 2-(3'-oxo-1'-propenyl)-malondialdehyde [(MDA)2] and (2) 2,4-dihydroxymethylene-3-(2,2-dimethoxyethyl)glutaraldehyde [(MDA)3Me2] and tested their mutagenicity in the Salmonella frameshift tester strains hisD3052 and TA94 (hisD3052/pKM101). Analysis of the reversion rates revealed both (MDA)2 and (MDA)3Me2 to be weak mutagens, approximately equipotent to MDA. Although both (MDA)2 and (MDA)3Me2 are mutagenic, the fact that their formation is thermodynamically unfavorable under physiological conditions suggests they do not contribute significantly to the mutagenicity of MDA solutions.

Malondialdehyde modification of proteins in vitro is enhanced in the presence of acetaldehyde.

To test the hypothesis that the cardioprotective effect of alcohol is related to the inhibition of malondialdehyde (MDA) modification of proteins by acetaldehyde (AA), we studied the effect of AA on MDA modification of bovine serum albumin (BSA) in vitro. BSA was incubated simultaneously with a fixed concentration of MDA (70 mM) and different concentrations of AA (120, 60, 30, 10, or 0 mM) for 24 h at 37 degrees C. The MDA-modified or AA-modified BSA was quantitated with immunoblotting by using specific anti-MDA and specific anti-AA protein antisera, respectively. In another set of experiments, BSA was incubated sequentially, first with different concentrations of AA and then with 70 mM of MDA. In both incubation protocols, the presence of AA and AA modification of BSA enhanced MDA binding. These in vitro observations suggest that the putative cardioprotective effects of alcohol or wine cannot be ascribed to AA-mediated reduction in MDA protein formation, a possible biochemical pathway of accelerated atherosclerosis.

LDL immunization induces T-cell-dependent antibody formation and protection against atherosclerosis.

Atherosclerosis is an inflammatory disease, and the involvement of immune mechanisms in disease progression is increasingly recognized. Immunization with oxidized low density lipoprotein (LDL) decreases atherosclerosis in several animal models. To explore humoral and cellular immune reactions involved in this protection, we immunized apolipoprotein E knockout mice with either homologous plaque homogenates or homologous malondialdehyde (MDA)-LDL. Immunization with both these antigen preparations reduced lesion development. The plaques contained immunogen(s) sharing epitopes on MDA-LDL, MDA-very low density lipoprotein, and oxidized cardiolipin. This shows that a T-cell-dependent antibody response was associated with protection against atherosclerosis. The protection was associated with specific T-cell-dependent elevation of IgG antibodies against MDA-LDL and oxidized phospholipids, and the increased titers of IgG antibodies were correlated with decreased lesion formation and lower serum cholesterol levels.

The urinary excretion of thiobarbituric acid reactive substances and malondialdehyde by normal adult males after consuming a diet containing salmon.

In this study we investigated the output of thiobarbituric acid reactive substances (TBARS) and malondialdehyde (MDA), as thiobarbituric acid (TBA)-MDA adduct, in the urine from subjects eating a diet in which the only source of n-3 long-chain, polyunsaturated fatty acids was fresh salmon. Nine healthy men, ages 30-65, were confined in the United States Department of Agriculture Western Human Nutrition Research Center, San Francisco, CA, for 100 d; food intake and exercise levels were controlled. All subjects were placed on a stabilization diet (StD) for 20 d, then six were fed the salmon diet for 40 d. The others remained on the StD. The groups switched diets for the last 40 d. Both diets were isocaloric (16% protein, 54% CHO and 30% fat by energy %). The salmon diet contained 7.5% of calories from n-6 fatty acids (FAs) and 2% from n-3 FAs, primarily eicosapentaenoic acid and docosahexaenoic acid in a 50:60 ratio, while the StD contained 7.5% from n-6 FAs and < 0.3% n-3 FAs (with presumably no significant amounts of C20 or C22 n-3 FAs). Twenty-four hour urinary output was collected, and 2% 3-d pool samples prepared for analysis of urinary TBARS and the TBA-MDA adduct. The total urinary output of each individual varied considerably, and on a daily basis the concentration of autoxidation products in an individual's urine varied also.(ABSTRACT TRUNCATED AT 250 WORDS)

Lens opacity induced by lipid peroxidation products as a model of cataract associated with retinal disease.

The cataractous lenses of patients with retinitis pigmentosa have been studied by electron microscopy. The posterior subcapsular opacities showed common ultrastructural features. Large areas of disruption of the lens fibre pattern were observed which showed an increase in the number of fibre membranes per unit area. In many regions an elaborate and regular folding of membranes was noted which produced complex 'figure-of-eight' and 'tramline' patterns, as well as membranous lamellar bodies. Masses of various size globules were also identified. It has been established that injection into the vitreous body of the rabbit eye of a suspension of liposomes prepared from phospholipids containing lipid peroxidation products induces the development of posterior subcapsular cataract. Such modelling of cataract is based on a type of clouding of the crystalline lens similar to that observed in cataract resulting from diffusion of toxic lipid peroxidation products from the retina to the lens through the vitreous body on degeneration of the photoreceptors. Saturated liposomes (prepared from beta-oleoyl-gamma-palmitoyl-L-alpha-phosphatidylcholine) do not cause clouding of the lens, which demonstrates the peroxide mechanism of the genesis of this form of cataract. Clouding of the lens is accompanied by accumulation of fluorescing lipid peroxidation products in the vitreous body, aqueous humor and the lens and also by a fall in the concentration of reduced glutathione in the lens. From the results it is concluded that lipid peroxidation may initiate the development of cataract.