Biomedical subjects

Omidreza Firuzi

Publications and source records attributed to Omidreza Firuzi.

7 recordsLinked to original sources

PubMed2006

Coxibs and Alzheimer's disease: should they stay or should they go?

The neuropathology of Alzheimer's disease (AD) is characterized by deposits of amyloid beta (Abeta) peptides and neurofibrillary tangles, but also, among other aspects, by signs of a chronic inflammatory process. Epidemiological studies have shown that long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) reduces the risk of developing AD and delays its onset. The classic target of NSAIDs is the prevention of cyclooxygenase (COX) activation. The main mechanism of action of COXs is the synthesis of prostaglandins, some of which have potent inflammatory activity. The discovery of two isoforms of this enzyme, COX-1 and COX-2, and that the latter is inducible by inflammatory cytokines supported the hypothesis that its inhibition would result in a potent antiinflammatory effect and led to the rapid development of selective COX-2 inhibitors, collectively called coxibs. Based on this rationale, some coxibs have been used in clinical trials for AD patients, but all the results obtained so far have been negative. Here, we review our knowledge in terms of COX-2 in the central nervous system, COX-2 and Abeta formation, and finally COX-2 and AD pathogenesis to understand the reasons why these drugs have failed and whether there is any scientific support to keep them as therapeutic tools for this chronic disease.

Alzheimer Disease↗

PubMed2006

Parameters of oxidative stress status in healthy subjects: their correlations and stability after sample collection.

It has been proposed that sample storage may have some influence on the parameters of oxidative stress status (OSS) in biological fluids. We measured four important OSS parameters in plasma of 23 healthy subjects and repeated the measurements in the same samples kept at -70 degrees C after different time intervals. Hydroperoxides and total antioxidant capacity (TAC) were determined by ferrous ion oxidation in presence of xylenol orange (FOX) and ferric reducing antioxidant power (FRAP) assays, respectively. Sulfhydryls and carbonyls were measured spectrophotometrically. In fresh samples, OSS seemed to increase with age and relatively good correlations were found among different parameters. The mean values of hydroperoxides (6.08 microM), TAC (0.334 mM Trolox equivalent), and sulfhydryls (0.562 mM) in fresh samples did not show any significant change after 1, 7, and 30 days of storage. Mean carbonyl concentration determined after 1 day storage (2.0 nmol/mg protein) did not change after 30 days. However, extents of changes in hydroperoxide concentrations varied considerably from one individual to another, even after 1 day. A similar phenomenon was observed in TAC, but after 7 days. We suggest measuring hydroperoxides in fresh samples and TAC maximally after 1 week. Sulfhydryls and carbonyls showed more stability and can be measured at least 1 month after sample collection.

Adult↗

PubMed2006

Oxidative stress parameters in different systemic rheumatic diseases.

The involvement of oxidative stress in the pathogenesis of rheumatic disorders, such as systemic sclerosis (SSc) and chronic polyarthritides, has been suggested yet not thoroughly verified experimentally. We analysed 4 plasmatic parameters of oxidative stress in patients with SSc (n = 17), psoriatic arthritis (PsA) (n = 10) and rheumatoid arthritis (RA) (n = 9) compared with healthy subjects (n = 22). The biomarkers were: total antioxidant capacity (TAC) measured by ferric reducing antioxidant power (FRAP) method, hydroperoxides determined by ferrous ion oxidation in presence of xylenol orange (FOX) method and sulfhydryl and carbonyl groups assessed by spectrophotometric assays. The results showed significantly increased hydroperoxides in SSc, PsA and RA (3.97 +/- 2.25, 4.87 +/- 2.18 and 5.13 +/- 2.36 micromol L(-1), respectively) compared with the control group (2.31 +/- 1.40 micromol L(-1); P < 0.05). Sulfhydryls were significantly lower in SSc (0.466 +/- 0.081 mmol L(-1)), PsA (0.477 +/- 0.059 mmol L(-1)) and RA (0.439 +/- 0.065 mmol L(-1)) compared with the control group (0.547 +/- 0.066 mmol L(-1); P < 0.05). TAC in all three diseases showed no difference in comparison with controls. Carbonyls were significantly higher in RA than in the control group (32.1 +/- 42 vs 2.21 +/- 1.0 nmol (mg protein)(-1); P < 0.05). The obtained data indicate augmented free radical-mediated injury in these rheumatic diseases and suggest a role for the use of antioxidants in prevention and treatment of these pathologies.

Adult↗

PubMed2004

Evaluation of the antioxidant activity of flavonoids by "ferric reducing antioxidant power" assay and cyclic voltammetry.

Flavonoids, naturally occurring phenolic compounds, have recently been studied extensively for their antioxidant properties. The structure-antioxidant activity relationships (SAR) of flavonoids have been evaluated against different free radicals, but "ferric reducing antioxidant power" (FRAP) assay, which determines directly the reducing capacity of a compound, has not been used for this purpose. In this study, the antioxidant activities of 18 structurally different flavonoids were evaluated by FRAP assay modified to be used in 96-well microplates. Furthermore, their oxidation potentials were also measured, which were in the range of +0.3 V (myricetin) to +1.2 V (5-hydroxy flavone) and were in good agreement with FRAP assay results. Quercetin, fisetin and myricetin had the lowest oxidation potentials and appeared the most active compounds in FRAP assay and were 3.02, 2.52 and 2.28 times more active than Trolox, respectively. Indications were found that the o-dihydroxy structure in the B ring and the 3-hydroxy group and 2,3-double bond in the C ring give the highest contribution to the antioxidant activity.

Antioxidants↗

PubMed2004

Hypochlorite scavenging activity of flavonoids.

Scavengers of hypochlorite, a highly reactive oxidant produced by activated phagocytes, could have potential therapeutic effects in diseases in which this oxidant plays a pathogenic role. Flavonoids are polyphenolic substances present in food plants and have been extensively studied for their antioxidant properties against various free radicals. Less is known about their reactivity with hypochlorite. In this study, the hypochlorite scavenging activity of flavonoids was investigated using a microplate assay recently developed in our laboratory. This method evaluates the ability of a substance to inhibit the formation of chloramines in human serum albumin upon oxidation by hypochlorite. Thirteen flavonoids were tested. Most of them inhibited human serum albumin oxidation at micro-molar concentrations and appeared more active than Trolox, a water-soluble equivalent of vitamin E. It was observed that the greater the number of hydroxyl substitutions, the greater the scavenging activity. The 3-hydroxy substitution seemed to be particularly important for scavenging activity, whereas the presence of a 2,3-double bond in the C ring did not. Flavonoids were found to be good hypochlorite scavengers in-vitro and further information is provided about the chemical aspects important for scavenging activity. Thus, flavonoids could have beneficial effects in diseases such as atherosclerosis in which hypochlorite plays a pathogenic role.

Antioxidants↗

PubMed2003

Hypochlorite scavenging activity of hydroxycinnamic acids evaluated by a rapid microplate method based on the measurement of chloramines.

Scavengers of hypochlorite (XOCl) could have beneficial effects in diseases in which this oxidant plays a pathogenic role. It has been reported that ferulic acid and chlorogenic acid, the quinic ester of caffeic acid, are good hypochlorite scavengers, but a systematic evaluation of the naturally occurring hydroxycinnamic acids (HCAs), which these substances belong to, has not been performed yet. Thus, in this work we studied, by two different in-vitro methods, the antioxidant activity of five HCAs: p-coumaric acid, ferulic acid, sinapinic acid, caffeic acid and chlorogenic acid. The methods applied in this study were based on the oxidation of human serum albumin (HSA) by XOCl, a new microplate method based on the measurement of chloramines and a previously described carbonyl assay. Firstly, lysine-derived chloramines, in the presence or absence of the HCAs, were detected using 5-thio-2-nitrobenzoic acid (TNB), measuring the absorbance at 415 nm by a microplate reader. To remove excess XOCl, Trolox, a known XOCl scavenger, was added before TNB. Secondly, lysine-derived carbonyls, in the presence or absence of the HCAs, were detected by using 2,4-dinitrophenylhydrazine. Hydroxycinnamic acids appeared active (caffeic >/= sinapinic > chlorogenic congruent with ferulic > p-coumaric acid) by both methods, suggesting possible pharmacological applications for these compounds, which are present at high concentrations in the plant kingdom.

Chloramines↗

PubMed2002

Development of a new assay for the screening of hypochlorous acid scavengers based on reversed-phase high-performance liquid chromatography.

A new assay for the screening of hypochlorite/hypochlorous acid (XOCl) scavengers, based on the reversed-phase high performance liquid chromatographic analysis of human serum albumin (HSA, 0.2% in 100 mM sodium phosphate, pH 7), before and after oxidation by XOCl (1.6 mM), was developed. XOCl induced a significant decrease of the area under the chromatographic peak of HSA at 280 nm due to the oxidation of the aromatic amino acids tryptophan and tyrosine, as suggested by the literature and by the chromatographic analyses and the electrochemical study performed here. The assay was validated by testing known XOCl scavengers such as ascorbic acid, cysteine, glutathione, S-methylglutathione and alpha-lipoic acid and other antioxidants such as carnosine and chlorogenic acid, which inhibited the oxidation of HSA. Quantitative activities were calculated using an original formula based on the changes of the area of the albumin peak. Electrochemical data collected here in a homogeneous medium showed that the anodic potentials of the antioxidants tested are less positive (ascorbic acid, chlorogenic acid and cysteine) or similar (alpha-lipoic acid) compared with those of the aromatic residues (tryptophan and tyrosine) of HSA oxidized by XOCl. However, as expected, carnosine, glutathione and S-methylglutathione were inactive at a glassy-carbon, gold or platinum electrode.

Antioxidants↗