Preliminary Data on the Interaction between Some Biometals and Oxidative Stress Status in Mild Cognitive Impairment and Alzheimer’s Disease Patients

Increased interest regarding the biometal mechanisms of action and the pathways in which they have regulatory roles was lately observed. Particularly, it was shown that biometal homeostasis dysregulation may lead to neurodegeneration including Alzheimer’s disease, Parkinson disease, or prion protein disease, since important molecular signaling mechanisms in brain functions implicate both oxidative stress and redox active biometals. Oxidative stress could be a result of a breakdown in metal-ion homeostasis which leads to abnormal metal protein chelation. In our previous work, we reported a strong correlation between Alzheimer’s disease and oxidative stress. Consequently, the aim of the present work was to evaluate some of the biometals’ levels (magnesium, manganese, and iron), the specific activity of some antioxidant enzymes (superoxide dismutase and glutathione peroxidase), and a common lipid peroxidation marker (malondialdehyde concentration), in mild cognitive impairment (n=15) and Alzheimer’s disease (n=15) patients, compared to age-matched healthy subjects (n=15). We found increased lipid peroxidation effects, low antioxidant defense, low magnesium and iron concentrations, and high manganese levels in mild cognitive impairment and Alzheimer’s disease patients, in a gradual manner. These data could be relevant for future association studies regarding the prediction of Alzheimer’s disease development risk or circling through stages by analyzing both active redox metals, oxidative stress markers, and the correlations in between

Assessing the Neurotoxicity of a Sub-Optimal Dose of Rotenone in Zebrafish (Danio rerio) and the Possible Neuroactive Potential of Valproic Acid, Combination of Levodopa and Carbidopa, and Lactic Acid Bacteria Strains

first_page settings Order Article Reprints Open AccessArticle Assessing the Neurotoxicity of a Sub-Optimal Dose of Rotenone in Zebrafish (Danio rerio) and the Possible Neuroactive Potential of Valproic Acid, Combination of Levodopa and Carbidopa, and Lactic Acid Bacteria Strains by Ovidiu-Dumitru Ilie 1,† [ORCID] , Raluca Duta 1, Ioana-Miruna Balmus 2,3, Alexandra Savuca 4 [ORCID] , Adriana Petrovici 5 [ORCID] , Ilinca-Bianca Nita 6, Lucian-Mihai Antoci 7, Roxana Jijie 8,† [ORCID] , Cosmin-Teodor Mihai 9 [ORCID] , Alin Ciobica 1,*, Mircea Nicoara 1,4 [ORCID] , Roxana Popescu 7,10 [ORCID] , Romeo Dobrin 11,* [ORCID] , Carmen Solcan 5,* [ORCID] , Anca Trifan 12,13 [ORCID] , Carol Stanciu 12,13 and Bogdan Doroftei 6 [ORCID] 1 Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University, Carol I Avenue, no 20A, 700505 Iasi, Romania 2 Department of Exact and Natural Sciences, Institute of Interdisciplinary Research, “Alexandru Ioan Cuza” University, Carol I Avenue, no 11, 700506 Iasi, Romania 3 Doctoral School of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University, Carol I Avenue, 20A, 700506 Iasi, Romania 4 Doctoral School of Geosciences, Faculty of Geography-Geology, “Alexandru Ioan Cuza” University, Carol I Avenue, no 20A, 700505 Iasi, Romania 5 Department of Molecular Biology, Histology and Embryology, Faculty of Veterinary Medicine, University of Life Sciences “Ion Ionescu de la Brad”, Mihail Sadoveanu Street, no 3, 700490 Iasi, Romania 6 Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, no 16, 700115 Iasi, Romania 7 Department of Medical Genetics, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, no 16, 700115 Iasi, Romania 8 Research Center on Advanced Materials and Technologies, Department of Exact and Natural Sciences, Institute of Inderdisciplinary Research, “Alexandru Ioan Cuza” University, Carol I Avenue, no 11, 700506 Iasi, Romania 9 Advanced Research and Development Center for Experimental Medicine (CEMEX), University of Medicine and Pharmacy “Grigore T. Popa”, University Street, no 16, 700115 Iasi, Romania 10 Department of Medical Genetics, “Saint Mary” Emergency Children’s Hospital, Vasile Lupu Street, no 62, 700309 Iasi, Romania add Show full affiliation list * Authors to whom correspondence should be addressed. † These authors equally contributed to this work. Antioxidants 2022, 11(10), 2040; https://doi.org/10.3390/antiox11102040 Received: 2 September 2022 / Revised: 3 October 2022 / Accepted: 13 October 2022 / Published: 17 October 2022 (This article belongs to the Special Issue Oxidative Stress and Neuroinflammation in Neurological and Neurodegenerative Disorders) Download Browse Figures Review Reports Versions Notes Abstract Parkinson’s disease (PD) is an enigmatic neurodegenerative disorder that is currently the subject of extensive research approaches aiming at deepening the understanding of its etiopathophysiology. Recent data suggest that distinct compounds used either as anticonvulsants or agents usually used as dopaminergic agonists or supplements consisting of live active lactic acid bacteria strains might alleviate and improve PD-related phenotypes. This is why we aimed to elucidate how the administration of rotenone (ROT) disrupts homeostasis and the possible neuroactive potential of valproic acid (VPA), antiparkinsonian agents (levodopa and carbidopa – LEV+CARB), and a mixture of six Lactobacillus and three Bifidobacterium species (PROBIO) might re-establish the optimal internal parameters. ROT causes significant changes in the central nervous system (CNS), notably reduced neurogenesis and angiogenesis, by triggering apoptosis, reflected by the increased expression of PARKIN and PINK1 gene(s), low brain dopamine (DA) levels, and as opposed to LRRK2 and SNCA compared with healthy zebrafish. VPA, LEV/CARB, and PROBIO sustain neurogenesis and angiogenesis, manifesting a neuroprotective role in diminishing the effect of ROT in zebrafish. Interestingly, none of the tested compounds influenced oxidative stress (OS), as reflected by the level of malondialdehyde (MDA) level and superoxide dismutase (SOD) enzymatic activity revealed in non-ROT-exposed zebrafish. Overall, the selected concentrations were enough to trigger particular behavioral patterns as reflected by our parameters of interest (swimming distance (mm), velocity (mm/s), and freezing episodes (s)), but sequential testing is mandatory to decipher whether they exert an inhibitory role following ROT exposure. In this way, we further offer data into how ROT may trigger a PD-related phenotype and the possible beneficial role of VPA, LEV+CARB, and PROBIO in re-establishing homeostasis in Danio rerio

Real-World Utilization of Corticosteroids in Severe Alcoholic Hepatitis: Eligibility, Response, and Outcomes

Background and Objectives: Alcoholic hepatitis (AH) poses a medical challenge, causing moderately severe to life-threatening episodes with high short- and long-term mortality. This study aimed to explore real-world corticosteroid utilization in severe AH, response predictors, and patient outcomes. Materials and Methods: We conducted a retrospective study on patients admitted for severe AH, defined as a Maddrey Discriminant Function score equal to or above 32, at a tertiary care center. We reviewed patients’ medical observation charts to identify corticosteroid prescriptions, reasons for ineligibility, and response rates. Responders were defined based on the Lille score, and predictors of non-response were identified. Short-term (one-month) and long-term (one-year) mortality rates were calculated according to treatment and response. Results: Out of 310 patients enrolled with severe AH, 59% received corticosteroids, achieving a response rate of 75.4%. The reasons for not administering corticosteroids were as follows: uncontrolled infections (27.6%), renal dysfunction (20.4%), gastrointestinal bleeding (18.9%), acute pancreatitis (7.1%), uncontrolled diabetes (3.1%), and other or unknown causes (22.8%). The overall 1-month mortality rate was 12.2%, higher in non-responders (35.3%) and patients who did not receive corticosteroids (13.4%) compared to responders (3.6%). The overall 1-year mortality rate was 62.5%, similar between patients who did not receive corticosteroids (78.7%) and non-responders (77.7%) and higher compared to responders (42.8%). Predictive factors for non-response included older age (OR = 1.05, 95%CI: 1.01–1.08), concomitant cirrhosis (OR= 2.11, 95% CI: 1.064–4.20), MELD scores exceeding 30 (OR = 2.42, 95% CI: 1.21–4.80), severe hypoalbuminemia (OR = 2.46, 95%CI: 1.12–5.37), and increased serum creatinine (OR = 1.5, 95% CI: 1.1–2.03). Among the prognostic scores, MELD 3.0 score exhibited superior efficacy for short-term (AUC = 0.734, 95% CI 0.656–0.811) and long-term mortality (AUC = 0.777, 95% CI: 0.724–0.830) compared to alternative scoring systems. Conclusions: Low eligibility rate and poor prognosis underscore the need for effective therapies. Our findings contribute to refining risk stratification and early prediction of non-response, aiding clinicians in identifying more beneficial therapies