Desirée Bartolini

Desirée Bartolini
Università degli Studi di Perugia | UNIPG · Pharmaceutical Sciences

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82
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Publications

Publications (82)
Article
Full-text available
Cryoprotective and cytoprotective agents (Cytoprotective Agents) are fundamental components of the cryopreservation process. This review presents the essentials of the cryopreservation process by examining its drawbacks and the role of cytoprotective agents in protecting cell physiology. Natural cryoprotective and cytoprotective agents, such as ant...
Article
Full-text available
Vitamin E (alpha-tocopherol) is an essential micronutrient and fat-soluble antioxidant with proposed role in protecting tissues from uncontrolled lipid peroxidation. This vitamin has also important protein function and gene modulation effects. The metabolism of vitamin E depends on hepatic binding proteins that selectively retain food alpha-tocophe...
Article
Full-text available
Adipose tissue (AT) is a remarkably plastic and active organ with functional pleiotropism and high remodeling capacity. Although the expansion of fat mass, by definition, represents the hallmark of obesity, the dysregulation of the adipose organ emerges as the forefront of the link between adiposity and its associated metabolic and cardiovascular c...
Article
Full-text available
The aim of our study was to investigate the plasma NGF concentration and TrkA/p75NTR receptor expression on white blood cells (WBCs), in peripheral and corpus cavernosum blood isolated from patients with erectile dysfunction and metabolic syndrome (ED/MetS). This was a pilot case–control study. Inclusion criteria were as follows: men 18–65 years wi...
Article
Melatonin (MLT) is a cytoprotective agent holding potential to prevent cadmium (Cd) toxicity and its impact in testicular function and fertility. Such potential was explored for the first time in porcine pre‐pubertal Sertoli cells (SCs). Cd toxicity in SCs resulted in impaired viability and function, abnormal H2O2 generation and efflux, and inducti...
Preprint
Adipose tissue (AT) is a remarkably plastic and active organ with functional pleiot-ropism and high remodeling capacity. Although the expansion of fat mass, by defini-tion, represents the hallmark of obesity, the dysregulation of the adipose organ emerges as the forefront of the link between adiposity and its associated metabolic and cardio-vascula...
Article
Full-text available
Background: Nerve Growth Factor (NGF) plays an important role in the reproductive system through its receptor's interaction (p75NTR). This paper aims to analyze the impact of NGF p75NTR in epididymal and ejaculated rabbit semen during in vitro sperm storage. Methods: Semen samples from 10 adult rabbit bucks were collected four times (n = 40) and...
Article
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Defining optimal nutrition in animals and humans remains a main scientific challenge. The objective of the work was to develop a dynamic model of reactive oxygen species (ROS)–polyunsaturated fatty acid (PUFA)–antioxidant homeostasis using the rabbit as a model. The problem entity was to evaluate the main metabolites generated from interactions bet...
Article
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Background: Healthcare-associated infections caused by multi-drug resistant (MDR) pathogens are associated with increased mortality and morbidity among hospitalized patients. Inanimate surfaces, and in particular high-touch surfaces, have often been described as the source for outbreaks of nosocomial infections. The present work aimed to evaluate...
Article
Full-text available
In this study, the phenol loading and antioxidant activity of wool yarn prepared with the aqueous extract of onion (Allium cepa L.) skin was enhanced by implementing the dyeing process with the use of alum as a mordant. Spectrophotometric and chromatographic methods were applied for the characterization of polyphenolic substances loaded on the wool...
Article
Sample manipulation for storage and storage itself, interfere with the stability of labile lipids in human plasma, including vitamin E (α-tocopherol), polyunsaturated fatty acids (PUFAs), and their enzymatic and free radical-derived oxidation metabolites. This remains a main limit of lipidomics studies that often lack of sufficient standardization...
Article
Full-text available
Unfolded protein response (UPR) and endoplasmic reticulum (ER) stress are aspects of SARS‐CoV‐2‐host cell interaction with proposed role in the cytopathic and inflammatory pathogenesis of this viral infection. The role of the NF‐kB pathway in these cellular processes remains poorly characterized. When investigated in VERO‐E6 cells, SARS‐CoV‐2 infec...
Article
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Viral infections sustain their replication cycle promoting a pro-oxidant environment in the host cell. In this context, specific alterations of the levels and homeostatic function of the tripeptide glutathione have been reported to play a causal role in the pro-oxidant and cytopathic effects (CPE) of the virus. In this study, these aspects were inv...
Article
Full-text available
The aim of this study was to establish the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on inanimate surfaces such as plastic, stainless steel, and glass during UV-C irradiation which is a physical means commonly utilized in sanitization procedures. The viral inactivation rate, virus half-life, and percentage of titer...
Article
Full-text available
SARS–CoV-2 (COVID-19) infection can cause a severe respiratory distress syndrome. The risk of severe manifestations and mortality characteristically increase in the elderly and in the presence of non-COVID-19 comorbidity. We and others previously demonstrated that the low molecular weight (LMW) and protein thiol/disulfide ratio declines in human pl...
Article
Full-text available
The metabolism of α-tocopherol (α-TOH, vitamin E) shows marked interindividual variability, which may influence the response to nutritional and therapeutic interventions with this vitamin. Recently, new metabolomics protocols have fostered the possibility to explore such variability for the different metabolites of α-TOH so far identified in human...
Article
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Aims: Anethole dithiolethione (ADT) is a marketed drug to treat xerostomia. Its mechanism of action is still unknown, but several preclinical studies indicate that it is able to increase intracellular glutathione (GSH) and protect against oxidative stress. Here, we investigated the molecular mechanisms behind these effects. Results: Oral treatme...
Article
Full-text available
Garcinoic acid (GA or δ-T3-13’COOH), is a natural vitamin E metabolite that has preliminarily been identified as a modulator of nuclear receptors involved in β-amyloid (Aβ) metabolism and progression of Alzheimer’s disease (AD). In this study, we investigated GA’s effects on Aβ oligomer formation and deposition. Specifically, we compared them with...
Article
Full-text available
Pregnane X receptor (PXR) is a master xenobiotic-sensing transcription factor and a validated target for immune and inflammatory diseases. The identification of chemical probes to investigate the therapeutic relevance of the receptor is still highly desired. In fact, currently available PXR ligands are not highly selective and can exhibit toxicity a...
Article
Recent findings suggest a functional interaction of the drug resistance enzyme glutathione S-transferase P (GSTP) with the transcription factor Nrf2, a master regulator of the adaptive stress response to cellular electrophiles. The effect of this interaction on the metabolism and redox of cellular thiols was investigated in this study during the ex...
Preprint
Pregnane X receptor (PXR) is a master xenobiotic-sensing transcription factor with a key role in drug metabolism and disposition. Its activity regulates a number of physiological processes in the liver and intestine, and it is now a validated target for human diseases associated with inflammation and dysregulation of the immune system. The identific...
Article
The trace element selenium (Se) is an essential component of selenoproteins and plays a critical role in redox signaling via regulating the activity of selenoenzymes such as thioredoxin reductase‐1 and glutathione peroxidases. Se compounds and its metabolites possess a wide range of biological functions including anticancer and cytoprotection effec...
Article
Melatonin (MLT) plays a role in preserving bone health, a function that may depend on homeostatic effects on both mature osteoblasts and mesenchymal stem cells (MSCs) of the bone tissue. In this study, these functions of MLT have been investigated in rat bone (femur) and in human adipose MSC (hMSC) during chronic exposure to low‐grade cadmium (Cd)...
Article
Glutamate-mediated excitotoxicity, neuroinflammation, and oxidative stress are common underlying events in neurodegeneration. This pathogenic “triad” characterizes the neurobiology of epilepsy, leading to seizure-induced cell death, increased susceptibility to neuronal synchronization and network alterations. Along with other maladaptive changes, t...
Article
Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease worldwide (about 25% of the general population) and 3-5% of patients develop non-alcoholic steatohepatitis (NASH), characterized by hepatocytes damage, inflammation and fibrosis, which increase the risk of developing liver failure, cirrhosis and hepat...
Article
Full-text available
2,2'-diselenyldibenzoic acid (DSBA) is a chemical probe produced to explore the pharmacological properties of diphenyldiselenide-derived agents with seleno-hormetic activity undergoing preclinical development. The present study was designed to verify in vivo the drug’s properties and to determine mechanistically how these may mediate the protection...
Article
Full-text available
Glutathione is considered the major non‐protein low molecular weight modulator of redox processes and the most important thiol reducing agent of the cell. The biosynthesis of glutathione occurs in the cytosol from its constituent amino acids, but this tripeptide is also present in the most important cellular districts, such as mitochondria, nucleus...
Article
The role of vitamin E in both enzymatic and free radical-dependent metabolism of polyunsaturated fatty acids (PUFAs) has been well demonstrated. This study proposed a new LC-MS/MS method to quantify the main vitamin E forms, their metabolites and main PUFA species in human blood, since, at present, there are not procedures able to simultaneously de...
Article
Full-text available
Two recent randomized controlled trials demonstrated improved radiographic, histological and hepatometabolic cues of non-alcoholic steatohepatitis (NASH) in pediatric patients treated with the ω-3 fatty acid docosahexaenoic acid (DHA) in combination with vitamin D (VD) or with choline (CHO) and vitamin E (VE), the DHA-VD and DHA-CHO-VE trials, resp...
Chapter
Enzymatic and non-enzymatic (free-radical-derived) metabolites of vitamin E are objects of increasing interest as both are indicators of the metabolism and biological functions of this fat-soluble vitamin. These include bioactive long-chain metabolites of alpha-tocopherol formed by the activity of cytochrome P450, which have recently been measured...
Article
Lipid peroxidation is one of the earliest pathogenic events of non-alcoholic fatty liver disease (NAFLD). In this context, an increased oxidation of the lipoperoxyl radical scavenger α-tocopherol (α-TOH) should occur already in the subclinical phases of the disease to compensate for the increase oxidation of the lipid excess of liver and possibly o...
Article
p38α mitogen-activated protein kinase (MAPK) is an attracting pharmacological target in inflammatory diseases and cancer. Searching for new and more efficient p38-MAPK inhibitors, two recently developed pyrazolobenzothiazine-based (COXP4M12 and COXH11) compounds were investigated in this study using a cellular model of p38 activation. This consiste...
Article
Full-text available
Seizure-triggered maladaptive neural plasticity and neuroinflammation occur during the latent period as a key underlying event in epilepsy chronicization. Previously, we showed that α-tocopherol (α-T) reduces hippocampal neuroglial activation and neurodegeneration in the rat model of kainic acid (KA)-induced status epilepticus (SE). These findings...
Preprint
Full-text available
2,2'-diselenyldibenzoic acid (DSBA) is a mild thiol peroxidase agent presently in preclinical development. This study reports that the drug has novel seleno-hormetic properties in both murine bone marrow and human liver cells. According with previous in vitro findings, mechanistic aspects of such properties were confirmed to include the activation...
Article
The glutathione (GSH) S-transferase family of detoxification and signalling proteins represents a major hub for the metabolism of Selenium-derived compounds. At the same time, these compounds can be used to modulate the expression and multiple activities of GSTs and other glutathione-dependent genes, that are important aspects in both the chemoprev...
Article
Specific microRNAs (miRs), including the “angio‐miR‐126” and the “inflamma‐miR‐146a‐5p,” have been proposed as biomarkers and even therapeutic targets of obesity‐associated metabolic diseases. Physical activity, a key measure of prevention for obesity and its complications, is reported to influence the expression of these miRs. In this study, we in...
Article
Hepatic lipid peroxidation is a key pathogenic event in the progression from NAFLD to the more severe inflammatory and fibrotic lesions of non-alcoholic steatohepatitis (NASH). This more advanced stage of the disease is a major risk factor for cirrhosis and hepatocellular carcinoma. Steatosis and inflammation of the liver are associated with an imp...
Article
In two consecutive randomized placebo-control trials, DHA has been used in combination with other micronutrient vitamins (choline (CHO), vitamin E as alpha-tocopherol and vitamin D) to treat obese nonalcoholic steatohepatitis (NASH) patients along with dietary restriction and physical activity. Regardless of micronutrient vitamins combination, the...
Article
Glutathione-S-transferase P-1 (GSTP) was recently proposed to interact with Nrf2 thus regulating its transcriptional activity. The possible consequences of such functional interaction on the metabolism and redox of cellular GSH remain unexplored and were investigated for the first time in this study using both genetic and pharmacological manipulati...
Article
Full-text available
In recent years, a large number of in silico and in vitro assays have been developed for safety assessment in early drug discovery. These methods are usually validated using datasets of known drugs with large chemical diversity, while application to homologous series has been rarely explored. Here we report a case study about phospholipidosis (PLD)...
Article
Deregulation of autophagy is proposed to play a key pathogenic role in hepatocellular carcinoma (HCC), the most common primary malignancy of the liver and the third leading cause of cancer death. Autophagy is an evolutionarily conserved catabolic process activated to degrade and recycle cell's components. Under stress conditions, such as oxidative...
Article
The enzymatic metabolism of vitamin E in liver cells generates long chain metabolites (LCMs) with proposed regulatory activity on inflammatory and atherogenic genes. In this study the LCM formation kinetics was characterized in HepG2 and HepaRG human hepatic cells, supplemented with RRR-α-tocopherol (α-TOH). α-13’OH was the main product of α-TOH me...
Article
Recently we described the role of glutathione-S-transferase P-1 (GSTP) expression in regulating Nrf2 transcriptional activity by protein-protein interaction. A functional interplay between Nrf2 and GSTP to control glutathione (GSH) biosynthesis, detoxification function and signal transduction through protein Cys glutathionylation can be hypothesize...
Article
p38 MAP kinases are a class of Ser/Thr kinases that link a number of extracellular stimuli to intracellular signaling pathways with effects on cellular processes such as cell cycle regulation, cell death, differentiation, senescence, cytokine production, etc. p38 kinase activation is nvolved in the pathogenesis of several inflammatory and oxidative...
Article
Full-text available
A sensitive and selective LC-MS/MS method for the quantification of vitamin E (α- and γ-tocopherol), polyunsaturated fatty acids (arachidonic, eicosapentaenoic, docosahexaenoic and α-linolenic acids) and their metabolites in human plasma and serum was developed and validated. The sample treatment consisted of an enzymatic hydrolysis followed by a d...
Article
This study aims at investigate in in vivo and in vitro models of non-alcoholic fatty liver disease (NAFLD) the enzymatic metabolism of α-tocopherol (vitamin E) and its relationship with vitamin E-responsive genes with key role in the lipid metabolism and detoxification of the liver. The experimental models included mice feed a high-fat diet combine...
Poster
Full-text available
A sensitive and selective LC-MS/MS method for the quantification of vitamin E (α- and γ-tocopherol), polyunsaturated fatty acids (arachidonic, eicosapentaenoic, docosahexaenoic and α-linolenic acids) and their metabolites in human plasma and serum was developed and validated. The sample treatment consisted of an enzymatic hydrolysis followed by a d...
Article
The expression of CYP4F2, a form of cytochrome P-450 with proposed role in α-tocopherol and long-chain fatty acid metabolism, was explored in HepG2 and HepaRG human hepatocytes during ethanol toxicity. Cytotoxicity, ROS production, and JNK and ERK1/2 kinase signaling increased in a dose and time-dependent manner during ethanol treatments; CYP4F2 g...
Chapter
In vitro and in vivo experimental models clearly demonstrate the efficacy of Se compounds as anticancer agents, contingent upon chemical structures and concentrations of test molecules, as well as on the experimental model under investigation that together influence cellular availability of compounds, their molecular dynamics and mechanism of actio...
Article
Selenium (Se) is an essential micronutrient that functions as "redox gatekeeper" and homeostasis factor of normal and cancer cells. Epidemiology and experimental studies, in the last years suggested that both inorganic and organic forms of Se may have favorable health effects. In this regard, a protective action of Se on cellular systems that may h...
Article
Context/objective: Increased oxidative stress in adipose tissue (AT) emerges as an inducer of obesity-linked insulin resistance. Here we tested the hypothesis whether free-radical derived oxysterols are formed by, and accumulate in, human adipocytes. Moreover, we asked whether increased accumulation of oxysterols characterizes the adipose cells of...
Article
Cytochrome P-450 mediated ω-oxidation is the earliest step in the enzymatic metabolism of vitamin E (tocopherols and tocotrienols). It generates the long chain carboxychromanol metabolites (α-LCMs) α-13’-OH and its corresponding carboxylic acid α-13’-COOH. These have been demonstrated to be active derivatives of vitamin E metabolism with in vitro e...
Article
Full-text available
Medulloblastoma (MB), a neuroectodermal tumor arising in the cerebellum, represents the most frequent childhood brain malignancy. Current treatments for MB combine radiation and chemotherapy and are often associated with relevant side effects; novel therapeutic strategies are urgently needed. N-(4-Hydroxyphenyl) retinamide (4-HPR, fenretinide), a s...
Data
Effects of fenretinide (4-HPR) on MB cell line proliferation. Fenretinide (100 nM-10 μM) inhibits DAOY and ONS-76 MB cell proliferation in a time and dose dependent manner, as shown by an MTT assay. Results are showed as Mean ± SEM, *p<0.05; **p<0.001 ***p<0.001 (two-way ANOVA). Three independent experiments, using 12 replicates were performed. (TI...
Article
After more than 90 years from its discovery and thousands of papers published, the physiological roles of vitamin E (tocopherols and tocotrienols) are still not fully elucidated. In the last few decades, the enzymatic metabolism of this vitamin has represented a stimulating subject for the scientific community. Its elucidation has opened up new hor...
Article
Glutathione S-transferase P (GSTP), and possibly other members of the subfamily of cytosolic GSTs, are increasingly proposed to have roles far beyond the classical GSH-dependent enzymatic detoxification of electrophilic metabolites and xenobiotics. Emerging evidence suggests that these are essential components of the redox sensing and signaling pla...
Article
Cytochrome P450-derived long-chain metabolites are gaining increasing interest as bioactive intermediates of vitamin E. In this study we first report on the HPLC-ECD and GC-MS analysis of the earliest metabolite of this vitamin, namely α-(13'-hydroxy)-6-hydroxychroman (α-13'-OH). The two chromatographic procedure are sensitive enough (LOQ of 10nM)...
Article
Aims Oxidative stress of adipose tissue (AT) emerges as an instigator of metabolic dysfunctions in obese insulin-resistant patients. Here we test the hypothesis whether free radical-derived cholesterol oxidation products (i.e., oxysterols) are: 1) generated in the dysfunctional “diabetic” AT, 2) secreted in AT interstitial fluid, 3) and active as m...
Article
Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease worldwide in association with oxidative stress and insulin resistance. Steatosis can evolve to steatohepatitis (NASH) by lipotoxicity, inflammation, fibrosis and cell death leading to cirrhosis and hepatocellular carcinoma. No valid therapy has been developed...
Article
Glutathione S-transferase π (GSTP), a phase II gene downstream of the Nrf2-ARE/EpRE transcription pathway, plays a key role in both the signaling and detoxification response to Se-organic compounds with thiol peroxidase activity. We here investigated the role of GSTP on the Nrf2 activation response of cells challenged with a new class of diselenide...
Article
Full-text available
Antimetabolites are a class of effective anticancer drugs interfering in essential biochemical processes. 5-Fluorouracil (5-FU) and its prodrug Capecitabine are widely used in the treatment of several solid tumors (gastro-intestinal, gynecological, head and neck, breast carcinomas). Therapy with fluoropyrimidines is associated with a wide range of...