Publications (16)58.89 Total impact
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Article: Whey protein, as exclusively nitrogen source, controls food intake and promotes glutathione antioxidant protection in Sprague-Dawley rats
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ABSTRACT: The inclusion of whey protein concentrates (WPC) in the diet can lead to a decrease in food intake. Considering that excessive food intake and weight gain are correlated with increased oxidative stress and other risk factors, the anorectic action of WPC may have important clinical implications. The aims of the current study were to verify the effects of WPC in comparison with those of casein on food intake, weight, and oxidized glutathione (GSSG) and total glutathione (GSH) concentrations in the blood and liver with or without oxidative stress induced by oral carbon tetrachloride intoxication. Male Sprague-Dawley rats were fed a balanced liquid diet for 3 weeks. Half of the rats received WPC (group P), while the control group received casein (group C). Group P rats ate significantly less than group C rats (p < 0.0001), and their weights decreased significantly. After carbon tetrachloride intoxication, there was a significant increase in GSH in rats of group P compared with the levels in rats of group C both in the liver (GSH group P 4,994 ± 652.6, group C 2,196 ± 323.2 nmol/mg, p < 0.01) and in the blood (GSH group P 1,368 ± 69.56, group C 1,088 ± 48.35 nmol/ml, p < 0.05). These findings indicate that WPC is effective in reducing food intake and preventing weight gain, and it may also play a protective role against oxidative stress by increasing glutathione synthesis in the liver.Mediterranean Journal of Nutrition and Metabolism 04/2012; 1(2):109-116. -
Article: Oxidative stress in the animal model: the possible protective role of milk serum protein
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ABSTRACT: In the field of biology, free radicals which are derived from the incomplete reduction of oxygen take on great importance; they belong to the so called reactive oxygen species, whose production in the organism is an inevitable consequence of various external or internal factors to which it is exposed. Once free radicals are generated they are often capable of giving rise to chain reactions. A lot of biological molecules are susceptible to the attack by free radicals including lipids, proteins, carbohydrates and nucleic acids. Molecular alterations caused by the radical reactions have been frequently studied and are considered as pathogenetically main passages in the development of many diseases and ageing. In order to face a radical attack, living organisms have developed several biological defensive systems against it: the main ones are represented by anti oxidizing molecules and by enzymatic anti oxidizing systems. Among the various defence systems, glutathione stands out as the principal guarantor of homoeostatic intra-cellular oxidation–reduction. One of glutathione’s most important functions is to act as cysteine “tank”; this amino acid is extremely unstable in the extra-cellular environment and it rapidly auto-oxidates. Whey proteins (WP) are particularly rich in cysteine (cys) and in glutamine (glu) and therefore potentially capable of increasing the organism’s antioxidant defences. It is thought that the principal mechanism which allows WPs to exert their properties is through the contribution of cys and glu, which is rich in these proteins and is used intra-cellularly for the synthesis of glutathione. A diet based on milk serum proteins which supplies a superior quantity of cys, allows for a greater synthesis of hepatic glutathione in oxidative stress conditions. The use of ultra-filtrated WP could represent a useful tool in the control of oxidative stress in numerous pathological situations. KeywordsWhey proteins (WP)-Glutathione-Antioxidant defences-Oxidative stress-ROS (reactive oxygen species)-Free radicalsMediterranean Journal of Nutrition and Metabolism 04/2012; 3(2):173-178. -
Article: Human mesangial cells resist glycoxidative stress through an antioxidant response.
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ABSTRACT: The generation of advanced glycation end-products (AGE), the interaction with their receptors, the generation of reactive oxygen species, and the modulation of intracellular redox equilibrium are believed to be the main factors causing alterations of mesangial cell physiology leading to diabetic nephropathy. Normal human primary mesangial cells were exposed to glycoxidative stress by culture in high glucose (HG) or treatment with AGE for up to 6 days. In both cases only a moderate generation of reactive oxygen species and production of HNE-protein adducts were induced while protein nitrotyrosination was not affected. Moreover, HG and AGE caused a significant antioxidant response, confirmed by the induction of heme oxygenase 1 and the consumption of vitamin E. Glutathione was decreased only by HG. Mesangial cell proliferation and viability were slightly affected by HG and AGE. Furthermore, both treatments failed to influence TGF-ß1 and MCP-1 secretion and to modulate RAGE and collagen IV expression. We believe that normal human mesangial cells can resist glycoxidative stress by the observed antioxidant response. These results support the concept that mesangial cells are only partly responsible for the onset and progression of diabetic nephropathy and that the role of other cell types, such as podocytes and endothelial cells, should be taken into consideration.International Journal of Molecular Medicine 02/2011; 27(2):213-9. · 1.98 Impact Factor -
Article: HNE‐dependent molecular damage in diabetic nephropathy and its possible prevention by N‐acetyl‐cysteine and oxerutin
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ABSTRACT: Accumulation of Advanced Lipoxidation End-products (ALE), such as MDA- and HNE-protein adducts, and Advanced Glycation End-products, such as carboxymethyl-lysine (CML), are probably involved in the development of diabetic nephropathy. In this study the effect of some antioxidant treatments (oxerutin, N-acetylcysteine, taurine and N-acetylcysteine+taurine) on kidney lipoxidative damage has been evaluated by immunohistochemistry in streptozotocined rats.Diabetic rats showed marked glomerular positivity for ALE, while the samples from Control rats were negative. All treatments except taurine were able to protect the glomeruli from ALE accumulation; the failure of taurine may be due to residual oxidative properties of its derivatives. These data are consistent with those of our previous study, which showed that all the antioxidants used except taurine protected the glomeruli from diabetes-induced enlargement, increased apoptotic rate, decreased cell density and CML accumulation.These data attest to a role of glycoxidative and lipoxidative damage in diabetes-dependent damage of the kidney, and indicate that specific antioxidants can prevent or attenuate diabetic nephropathy.BioFactors 12/2008; 24(1‐4):291 - 298. · 4.93 Impact Factor -
Article: Mechanisms of BSO (L-buthionine-S,R-sulfoximine)-induced cytotoxic effects in neuroblastoma.
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ABSTRACT: Glutathione (GSH) depletion is widely used to sensitize cells to anticancer treatment inducing the progression of programmed cell death and overcoming chemoresistance. It has been reported that neuroblastoma cells with MYCN amplification are unable to start TRAIL-dependent death and MYCN, in concert with cytotoxic drugs, efficiently induces the mitochondrial pathway of apoptosis through oxidative mechanisms. In this study, we show that GSH loss induced by L-buthionine-S,R-sulfoximine (BSO), an inhibitor of GSH biosynthesis, leads to overproduction of reactive oxygen species (ROS) and triggers apoptosis of MYCN-amplified neuroblastoma cells. BSO susceptibility of SK-N-BE-2C, a representative example of MYCN-amplified cells, has been attributed to stimulation of total SOD activity in the absence of changes in the level and the activity of catalase. Therefore, the unbalanced intracellular redox milieu has been demonstrated to be critical for the progression of neuroblastoma cell death that was efficiently prevented by antioxidants and rottlerin. These results describe a novel pathway of apoptosis dependent on ROS formation and PKC-delta activation and independent of p53, bcl-2, and bax levels; the selective redox modulation of PKC-delta might be suggested as a potential strategy for sensitizing MYCN-amplified cells to therapeutic approaches.Free Radical Biology and Medicine 03/2008; 44(3):474-82. · 5.42 Impact Factor -
Article: GSH loss per se does not affect neuroblastoma survival and is not genotoxic.
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ABSTRACT: Depletion of glutathione (GSH) by buthionine sulfoximine (BSO) has been reported to be toxic against some cancer cells and to sensitize many tumours including neuroblastoma (NB) to anticancer drugs. The balance between the production rate of reactive oxygen species (ROS) and the function of GSH affects the intracellular reduction-oxidation status, which is crucial for the regulation of several cellular physiological functions. To assess the role of glutathione in neuroblastoma therapy, the effect of sublethal concentrations of BSO was studied in a panel of neuroblastoma cell lines characterized by different MYCN status. We found that GSH depletion per se not accompanied by ROS overproduction, does not affect cell survival, and is not genotoxic but induces HO-1 expression in GI-ME-N cell line, a representative example of MYCN non-amplified NB cells, having the highest basal levels of GSH among the tested NB lines. These observations might open a novel therapeutic window based on the possibility of modulating the cellular 'activity' of GSH.International Journal of Oncology 02/2008; 32(1):121-7. · 2.40 Impact Factor -
Article: Heme oxygenase 1 expression in rat liver during ageing and ethanol intoxication.
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ABSTRACT: Heme oxygenase 1 (HO-1) expression is recognized as a marker of cellular response to oxidative stress; since ageing is believed to be related to oxidative "wear and tear", HO-1 may represent a candidate biomarker of ageing. In our study, the hepatic expression of HO-1 mRNA, evaluated by RT-PCR in 2.5-24 month-old rats, was higher at 6 months than at 2.5 months of age, but thereafter increased no further: on the contrary, a declining trend was observed. However, while 2.5 month-old rats responded to acute ethanol intoxication by displaying increased expression of liver HO-1 mRNA, and 6 month-old rats exhibited a mild response, 18 month-old rats did not show any response; this phenomenon suggests that during development and ageing the transcriptional response to oxidative stress decreases. In our view, the finding that HO-1 expression did not increase progressively during ageing may be explained by a decreased transcriptional ability to respond to stress in older animals, rather than by a reduction in oxidative stress.Biogerontology 07/2007; 8(3):365-72. · 3.34 Impact Factor -
Article: Oxidative stress and antioxidant defence in a healthy nonagenarian population.
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ABSTRACT: Results on oxidative markers during ageing are not consistent throughout the scientific literature; however, successful ageing may depend on better ability to cope with oxidative stress. A previous study of ours showed that successful ageing could actually be related to enhanced response to oxidatively modified proteins. In this study, a healthy nonagenarian population (OVER-90) was examined for various blood oxidative biomarkers and compared with a healthy population of blood donors (age range, 23-66 years). Blood glutathione, both total (tGSH) and oxidised (GSSG), and total plasmatic antioxidant status were maintained in the OVER-90 at a level similar to the control population. Sulphydryl (sulfhydryl) groups and glutathione peroxidase (GPx) were instead decreased. The results are discussed in a possible unifying view: the OVER-90 population could possess a globally preserved antioxidant ability, though some signs of oxidative damage are present and some structures could be 'sacrificed' in order to keep the redox equilibrium.Redox report: communications in free radical research 02/2007; 12(1):59-62. · 1.51 Impact Factor -
Article: Oxidative stress and antioxidant defence in a healthy nonagenarian population
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ABSTRACT: Results on oxidative markers during ageing are not consistent throughout the scientific literature; however, successful ageing may depend on better ability to cope with oxidative stress. A previous study of ours showed that successful ageing could actually be related to enhanced response to oxidatively modified proteins. In this study, a healthy nonagenarian population (OVER-90) was examined for various blood oxidative biomarkers and compared with a healthy population of blood donors (age range, 23–66 years). Blood glutathione, both total (tGSH) and oxidised (GSSG), and total plasmatic antioxidant status were maintained in the OVER-90 at a level similar to the control population. Sulphydryl (sulfhydryl) groups and glutathione peroxidase (GPx) were instead decreased. The results are discussed in a possible unifying view: the OVER-90 population could possess a globally preserved antioxidant ability, though some signs of oxidative damage are present and some structures could be 'sacrificed' in order to keep the redox equilibrium.Redox Report 01/2007; 12(1-2):59-62. · 1.73 Impact Factor -
Article: The increased activity of BACE1 correlates with oxidative stress in Alzheimer's disease.
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ABSTRACT: We evaluated expression, protein levels and activity of the Beta-site cleaving enzyme (BACE1) as well as the amount of products of lipid peroxidation in frontal cortex of three groups of cases: sporadic Alzheimer's disease (AD); control subjects (CTR); cognitively normal subjects with abundant amyloid plaques (NA). We found a significant increase of BACE1 activity and products of lipid peroxidation in brain tissue of AD cases, with normal gene expression, and non-significant elevation of protein levels. CTR and NA samples showed similar levels of BACE1 activity and oxidative products. BACE1 activity and the amount of oxidative products were significantly correlated in all cases.Moreover, both BACE1 activity and the level of 4-hydroxynonenal were correlated with the amount of Beta-amyloid pyroglutamated 3-42, the more toxic Beta-amyloid peptide that is characteristic of AD. These findings suggest that BACE1 activity reflects the type of ABeta species, rather than the Beta-amyloid plaques load. Hence, the increase of BACE1 activity occurring in sporadic AD is likely the effect, rather the cause, of ABeta accumulation and oxidative stress.Neurobiology of aging 07/2006; 28(7):1009-14. · 5.94 Impact Factor -
Article: Supplementation with N-acetylcysteine and taurine failed to restore glutathione content in liver of streptozotocin-induced diabetics rats but protected from oxidative stress.
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ABSTRACT: Rats were rendered diabetic with streptozotocin and supplemented or not with N-acetylcysteine (NAC) and taurine (TAU). The liver was examined for the quantity of glutathione (GSH), both total and oxidised (GSSG), by HPLC assay. Moreover, the liver expression of gamma-glutamyl-cysteine synthetase, cysteine dioxygenase and heme oxygenase 1 was evaluated. Streptozotocin-diabetic rats showed decreased levels of liver glutathione (GSH); dietary supplementation with the antioxidants NAC and TAU failed to restore liver GSH to the level of control rats. Gamma-glutamyl-cysteine synthetase expression was not reduced in the diabetic rats, so the low hepatic GSH level in the supplemented diabetic rats cannot be ascribed to decreased expression of the biosynthetic key enzyme. Moreover, the diabetic rats showed no evidence of increased expression of cysteine dioxygenase, which could have indicated that NAC-derived cysteine was consumed in metabolic pathways different from GSH synthesis. However, NAC+TAU treatment provided partial protection from glutathione oxidation in the liver of diabetic rats; moreover, the antioxidant treatment reduced the hepatic overexpression of heme oxygenase 1 (HO-1) mRNA which was detected in the diabetic rats. In conclusion, although NAC was not able to restore liver GSH levels, the antioxidant treatment restrained GSH oxidation and HO-1 overexpression, which are markers of cellular oxidative stress: diabetic rats probably exploit NAC as an antioxidant itself rather than as a GSH precursor.Biochimica et Biophysica Acta 07/2005; 1741(1-2):48-54. · 4.66 Impact Factor -
Article: HNE-dependent molecular damage in diabetic nephropathy and its possible prevention by N-acetyl-cysteine and oxerutin.
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ABSTRACT: Accumulation of Advanced Lipoxidation End-products (ALE), such as MDA- and HNE-protein adducts, and Advanced Glycation End-products, such as carboxymethyl-lysine (CML), are probably involved in the development of diabetic nephropathy. In this study the effect of some antioxidant treatments (oxerutin, N-acetylcysteine, taurine and N-acetylcysteine+taurine) on kidney lipoxidative damage has been evaluated by immunohistochemistry in streptozotocined rats. Diabetic rats showed marked glomerular positivity for ALE, while the samples from Control rats were negative. All treatments except taurine were able to protect the glomeruli from ALE accumulation; the failure of taurine may be due to residual oxidative properties of its derivatives. These data are consistent with those of our previous study, which showed that all the antioxidants used except taurine protected the glomeruli from diabetes-induced enlargement, increased apoptotic rate, decreased cell density and CML accumulation. These data attest to a role of glycoxidative and lipoxidative damage in diabetes-dependent damage of the kidney, and indicate that specific antioxidants can prevent or attenuate diabetic nephropathy.BioFactors 02/2005; 24(1-4):291-8. · 4.93 Impact Factor -
Article: Malondialdehyde, a lipoperoxidation-derived aldehyde, can bring about secondary oxidative damage to proteins.
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ABSTRACT: Lipoperoxidation-derived aldehydes, for example malondialdehyde (MDA), can damage proteins by generating covalent adducts whose accumulation probably participates in tissue damage during aging. However, the mechanisms of adduct formation and their stability are scarcely known. This article investigates whether oxidative steps are involved in the process. As a model of the process, the interaction between MDA and bovine serum albumin (BSA) was analyzed. Incubation of BSA with MDA resulted in rapid quenching of tryptophan fluorescence and appearance of MDA protein adduct fluorescence; transition metal ion traces interfered with the latter process. MDA induced generation of peroxides in BSA, which was preventable with the antioxidant 2,6,-di-tert-butyl-4-methylphenol (BHT). MDA-exposed BSA underwent aggregation, degradation, and BHT-sensitive "gel retardation" effects. Phycoerythrin fluorescence disappearance, a marker of damage mediated by reactive oxygen species, indicated synergism between MDA and metal ions. The interaction between reactive aldehydes and proteins is likely to occur in several steps, some of them oxidative in nature, giving rise to advanced lipoperoxidation end-products, which could participate, with advanced glycation end-products, in the generation of tissue damage during aging.The Journals of Gerontology Series A Biological Sciences and Medical Sciences 10/2004; 59(9):B890-5. · 4.60 Impact Factor -
Article: Anti malondialdehyde-adduct immunological response as a possible marker of successful aging.
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ABSTRACT: Contrasting results have been obtained by various researchers about oxidative markers of aging. In this study, a healthy over-90-year-old population was examined for various plasma oxidative biomarkers and compared with a healthy population of blood donors (age range 23-66). Plasma malondialdehyde (MDA), evaluated by means of the thiobarbituric acid test, was significantly higher in the over-90-year-old population, confirming the presence of increased lipoperoxidation in old age. The antibody titre against MDA-protein adducts, considered a marker of lipoperoxidative protein damage in vivo, was evaluated in an ELISA test, completely home made and calibrated versus a concentrated pool of human plasma; this antibody titre was significantly higher in the over-90-year-old population. Plasma vitamin E, evaluated in RP-HPLC, was not significantly different between the two groups. Plasma protein-bound carbonyls, a marker of oxidative protein damage, were measured with the 2,4-dinitrophenylhydrazine assay; their level in the over-90-year-old population was lower than in the blood donors. The higher antibody titre against MDA-adducts may result in protection against accumulation of oxidatively damaged proteins by enhancing their removal, and, together with the preserved plasma vitamin E level, it may endow over-90-year-olds with an especially efficient antioxidant profile. The low level of protein carbonyl might reflect the more efficient removal of damaged proteins.Experimental Gerontology 11/2003; 38(10):1129-35. · 3.74 Impact Factor -
Article: Role of PKC-delta activity in glutathione-depleted neuroblastoma cells.
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ABSTRACT: Protein kinases C (PKCs) are a family of isoenzymes sensitive to oxidative modifications and involved in the transduction signal pathways that regulate cell growth. As such, they can act as cellular sensors able to intercept intracellular redox changes and promote the primary adaptive cell response. In this study, we have demonstrated that PKC isoforms are specifically influenced by the amount of intracellular glutathione (GSH). The greatest GSH depletion is associated with a maximal reactive oxygen species (ROS) production and accompanied by an increase in the activity of the delta isoform and a concomitant inactivation of alpha. ROS generation induced early morphological changes in GSH-depleted neuroblastoma cells characterized, at the intracellular level, by the modulation of PKC-delta activity that was involved in the pathway leading to apoptosis. When cells were pretreated with rottlerin, their survival was improved by the ability of this compound to inhibit the activity of PKC-delta and to counteract ROS production. These results define a novel role of PKC-delta in the cell signaling pathway triggered by GSH loss normally associated with many neurodegenerative diseases and clinically employed in the treatment of neuroblastoma.Free Radical Biology and Medicine 10/2003; 35(5):504-16. · 5.42 Impact Factor -
Article: Comparative trial of N-acetyl-cysteine, taurine, and oxerutin on skin and kidney damage in long-term experimental diabetes.
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ABSTRACT: This study analyzes the effect of chronic treatment with different antioxidants (N-acetyl-cysteine [NAC], taurine, a combination of NAC and taurine, and oxerutin) on long-term experimental diabetes induced by streptozotocin in rats. Glycoxidative damage was evaluated in the skin; glomerular structural changes were studied with morphometry and immunohistochemistry. Oxerutin treatment and the combined NAC plus taurine treatment resulted in reduced accumulation of collagen-linked fluorescence in skin in comparison with untreated diabetic rats. All treatments except taurine reduced glomerular accumulation of N(epsilon)-(carboxymethyl)lysine and protected against the increase in glomerular volume typical of diabetes; furthermore, the apoptosis rate was significantly decreased and the glomerular cell density was better preserved. Glycoxidative markers in the skin turned out to be good indicators of the glomerular condition. The findings that emerged from our study support the hypothesis that glomerular damage in diabetes can be prevented or at least attenuated by supplementation with specific antioxidants. Treatment with oxerutin and combined treatment with NAC plus taurine gave the most encouraging results, whereas the results of taurine-only treatment were either negligible or negative and therefore suggest caution in the use of this molecule in single-drug treatment courses.Diabetes 03/2003; 52(2):499-505. · 8.29 Impact Factor
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2005–2012
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Università degli Studi di Genova
Genova, Liguria, Italy
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