Discovery by a proteomic approach of possible early biomarkers of drug-induced nephrotoxicity in medication-overuse headache

Bellei, Elisa; Monari, Emanuela; Cuoghi, Aurora; Bergamini, Stefania; Guerzoni, Simona; Ciccarese, Michela; Özben, Tomris; Tomasi, Aldo; Pini, Luigi Alberto

doi:10.1186/1129-2377-14-6

Cited by 17 publications

(42 citation statements)

References 32 publications

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“…T h e ba nd s w ho s e mo l e c u l a r w e i g ht corresponded to vitellogenin (180 kDa) and apolipophorins (250 kDa) were cut from the gels, digested in-gel with trypsin and finally analysed by a Nano LC-CHIP-MS system (ESI-Q-TOF 6520; Agilent Technologies) as previously described (Bellei et al 2013). Raw mass spectrometry data were processed to obtain the Mascot generic files for database searching.…”

Section: Protein Identification By Mass Spectrometrymentioning

confidence: 99%

Biomarkers of nutritional status in honeybee haemolymph: effects of different biotechnical approaches for Varroa destructor treatment and wintering phase

et al. 2018

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Oxalic acid achieves its maximum efficacy against Varroa destructor during the active season only when coupled with brood manipulation techniques like brood interruption and brood removal. This study aimed to assess the impact of these manipulations on the colony nutritional status and the subsequent wintering phase, focusing on selected haemolymph biomarkers: total proteins (TP), zinc (Zn), vitellogenin (VG) and apolipophorin (APO). Twenty-five days after the manipulations (T1), colonies that underwent brood interruption (BI) stored more TP and VG than colonies in the brood removal group (BR), with a lower APO percentage, suggesting a lower metabolic effort in summer. In winter, honeybee colonies of all groups reached similar concentrations of the abovementioned parameters, but colonies in the BI group showed a higher population. TP, VG and APO are shown to be promising biomarkers of nutritional status of the colony. Basing on the results obtained, we suggest brood interruption coupled with oxalic acid as the preferred organic method for the control of V. destructor in summer.

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Section: Protein Identification By Mass Spectrometrymentioning

confidence: 99%

Biomarkers of nutritional status in honeybee haemolymph: effects of different biotechnical approaches for Varroa destructor treatment and wintering phase

et al. 2018

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“…Preclinical studies have shown that repeated or continuous treatment with antimigraine drugs result in persistent up-regulation of neurotransmitters within the orofacial division of the trigeminal ganglia and in the development of CA in response to migraine triggers, even weeks after discontinuation of the antimigraine drug [ 7 ]. In our previous study we found elevated urinary levels of Prostaglandin-H2 D-synthase (PTGDS) in 3 MOH patient groups (triptans, NSAIDs and mixture abusers) in respect to healthy non-abusers individuals as control group [ 8 ]. Prostaglandin D2 is the most abundant prostanoid produced in the central nervous system of mammals, and is implicated in the modulation of neural functions, such as sleep induction, regulation of body temperature, nociception, pain responses and allodynia [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Validation of potential candidate biomarkers of drug-induced nephrotoxicity and allodynia in medication-overuse headache

et al. 2015

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BackgroundMedication-overuse headache (MOH) is a chronic disorder that results from the overuse of analgesics drugs, triptans or other acute headache compounds. Although the exact mechanisms underlying MOH remain still unknown, several studies suggest that it may be associated with development of “central sensitization”, which may cause cutaneous allodynia (CA). Furthermore, the epidemiology of drug-induced disorders suggests that medication overuse could lead to nephrotoxicity. The aim of this work was to confirm and validate the results obtained from previous proteomics studies, in which we analyzed the urinary proteome of MOH patients in comparison with healthy non-abusers individuals.MethodsMOH patients were divided into groups on the basis of the drug abused: triptans, non-steroidal anti-inflammatory drugs (NSAIDs) and mixtures, (mainly containing indomethacin, paracetamol and, in some cases, caffeine). Healthy subjects, with a history of normal renal function, were used as controls. In this study, four proteins that were found differentially expressed in urine, and, on the basis of the literature review, resulted related to kidney diseases, were verified by Western Blot and Enzyme-linked Immunosorbent Assay (ELISA); Prostaglandin-H2 D-synthase (PTGDS), uromodulin (UROM), alpha-1-microglobulin (AMBP) and cystatin-C (CYSC).ResultsWestern blot analysis allowed to validate our previous proteomics data, confirming that all MOH patients groups show a significant over-excretion of urinary PTGDS, UROM, AMBP and CYSC (excluding triptans group for this latter), in comparison with controls. Moreover, the expression of PTGDS was further evaluated by ELISA. Also by this assay, a significant increase of PTGDS was observed in all MOH abusers, according to 2-DE and Western blot results.ConclusionsIn this study, we confirmed previous findings concerning urinary proteins alterations in MOH patients, identified and demonstrated the over-expression of PTGDS, UROM, AMBP, and CYSC, particularly in NSAIDs and mixtures abusers. Over-expression of these proteins have been related to renal dysfunction and probably, PTGDS, to the development of CA. The detection and confirmation of this proteins pattern represent a promising tool for a better understanding of potential nephrotoxicity induced by drugs overuse and may enhance awareness related to the MOH-associated risks, even in absence of clinical symptoms.

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“…L-PGDS was already found at unusually high concentrations in urine of MOH patients [13,14]. The enzyme is highly expressed in leptomeninges [30] and is physiologically eliminated via the kidney.…”

Section: Discussionmentioning

confidence: 97%

Exploration of candidate serum biomarkers potentially related to the chronic pain condition in Medication Overuse Headache

Pellesi

Bellei

Guerzoni

et al. 2019

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Background Medication Overuse Headache (MOH) is a prevalent and disabling disorder resulting from the overuse of analgesic drugs, triptans or other acute headache medications. In previous proteomic studies, several proteins have been found at high concentrations in the urine of MOH patients and in the serum of rats with neuropathic pain. The aim of this study was to compare the serum levels of lypocalin-type Prostaglandin D2 synthase (L-PGDS), Vitamin D-binding protein (VDBP), apolipoprotein E (APOE) and apolipoprotein A1 (APOA1) in MOH patients and healthy individuals, further exploring their relationship with cutaneous pain thresholds (CPTs) in the territories innervated by the trigeminal nerve. Methods 69 MOH patients and 42 age- and sex-matched healthy volunteers were enrolled in the study. Von Frey-like filaments were applied to the skin territories innervated by the trigeminal nerve, to determine the CPTs. L-PGDS, VDBP, APOE and APOA1 were quantified in the serum by Enzyme-linked Immunosorbent Assay (ELISA). Clinical and laboratory data were collected. Comparisons between MOH patients and healthy individuals were performed using independent t test or χ2 test. To correlate serum proteins with CPTs, Pearson correlation coefficient or Spearman's rank correlation coefficient were used. Results CPTs were lower among MOH patients. L-PGDS, VDBP and APOE had significantly different serum concentrations between groups (p < 0.01), but no correlation was found with CPTs. APOA1 serum concentrations did not differ between patients and healthy individuals. Conclusions L-PGDS, VDBP and APOE had abnormal serum levels in MOH patients, confirming their alteration in some conditions of chronic headache and neuropathic pain. However, they had no relationship with CPTs. The in-depth study of serum proteins represents a promising approach for a better understanding of MOH, as well as the detection of candidate biomarkers for chronic headache or the risks associated with overuse medications.

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Discovery by a proteomic approach of possible early biomarkers of drug-induced nephrotoxicity in medication-overuse headache

Cited by 17 publications

References 32 publications

Biomarkers of nutritional status in honeybee haemolymph: effects of different biotechnical approaches for Varroa destructor treatment and wintering phase

Biomarkers of nutritional status in honeybee haemolymph: effects of different biotechnical approaches for Varroa destructor treatment and wintering phase

Validation of potential candidate biomarkers of drug-induced nephrotoxicity and allodynia in medication-overuse headache

Exploration of candidate serum biomarkers potentially related to the chronic pain condition in Medication Overuse Headache

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