Ibogaine Induces Cardiotoxic Necrosis in Rats-The Role of Redox Processes.

Ibogaine is an organic indole alkaloid that is used in alternative medicine to combat addiction. Numerous cases of life-threatening complications and sudden deaths associated with ibogaine use have been reported, and it has been hypothesized that the adverse effects are related to ibogaine's tendency to induce cardiac arrhythmias. Considering that the bioavailability of ibogaine and its primary metabolite noribogaine is two to three times higher in female rats than in male rats, we here investigated the effect of a single oral dose (1 or 20 mg/kg) of ibogaine on cardiac histopathology and oxidative/antioxidant balance.

Influence of Long-Term Anti-Seizure Medications on Redox Parameters in Human Blood.

Background: Epilepsy is a chronic brain disease affecting millions of people worldwide, but little is known about the impact of anti-seizure medications on redox homeostasis.

Methods: This study aimed to compare the effects of the long-term use of oral anti-seizure medications in monotherapy (lamotrigine, carbamazepine, and valproate) on antioxidant enzymes: superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, haemoglobin, and methaemoglobin content in erythrocytes, and concentrations of total proteins and thiols, nitrites, lipid peroxides and total glutathione in the plasma of epilepsy patients and drug-naïve patients.

Results: The results showed that lamotrigine therapy led to lower superoxide dismutase activity ( < 0.

Humoral and Cellular Immune Response after Three Doses of Sinopharm [Vero Cell]-Inactivated COVID-19 Vaccine in Combination with SARS-CoV-2 Infection Leads to Hybrid Immunity.

Background: Several vaccines against COVID-19 have been developed and licensed to enhance the immune response against SARS-CoV-2. Similarly, previous infection with SARS-CoV-2 has been shown to provide significant protection against severe infection and hospitalization.

Methods: We investigated the effect of three doses of the Sinopharm vaccine and SARS-CoV-2 infection on the specific immune response in 103 volunteers, measuring neutralizing antibodies, anti-S1 IgG, anti-RBD IgM, anti-N IgM, anti-N IgG antibodies, and INF γ.

Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?

Packed with hemoglobin, an essential protein for oxygen transport, human erythrocytes are a suitable model system for testing the pleiotropic effects of lipophilic drugs. Our study investigated the interaction between antipsychotic drugs clozapine, ziprasidone, sertindole, and human hemoglobin under simulated physiological conditions. Analysis of protein fluorescence quenching at different temperatures and data obtained from the van't Hoff diagram and molecular docking indicate that the interactions are static and that the tetrameric human hemoglobin has one binding site for all drugs in the central cavity near αβ interfaces and is dominantly mediated through hydrophobic forces.

The humanised CYP2C19 transgenic mouse exhibits cerebellar atrophy and movement impairment reminiscent of ataxia.

Aims: CYP2C19 transgenic mouse expresses the human CYP2C19 gene in the liver and developing brain, and it exhibits altered neurodevelopment associated with impairments in emotionality and locomotion. Because the validation of new animal models is essential for the understanding of the aetiology and pathophysiology of movement disorders, the objective was to characterise motoric phenotype in CYP2C19 transgenic mice and to investigate its validity as a new animal model of ataxia.

Methods: The rotarod, paw-print and beam-walking tests were utilised to characterise the motoric phenotype.

Evaluation of Tick Abundance and Pyrethroid Resistance Via Determination of Glutathione-S-Transferases Activity.

Controlling the number of ticks as carriers of infectious diseases is very important. The process is sometimes compromised by activating the protective mechanisms of the tick itself. Glutathione-S-transferases activity (GSTs) was the subject of our investigation of tick abundance after pyrethroid treatment.

Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis.

Sexual dysfunction, as a noticeable adverse effect of atypical antipsychotic drugs (APDs) for the treatment of schizophrenia, has not been investigated in detail. A study was undertaken to investigate whether 28-day long treatment with clozapine, ziprasidone or sertindole (using a recommended daily dose for atypical antipsychotic therapy), induced histopathological changes both in rat testicles and prostate, changed the activity of the antioxidant defence system and altered blood testosterone and prolactin. Clozapine, ziprasidone and sertindole induced histopathological changes in rat testicular tissue, which could be attributed to a disturbed testicular antioxidant defence system in addition to an altered prolactin to testosterone ratio.

Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function.

The effects of a fructose-rich diet and chronic stress on copper metabolism in the kidneys are still understudied. We investigated whether fructose and/or chronic unpredictable stress modulate copper metabolism in a way that affects redox homeostasis, thus contributing to progression of metabolic disturbances in the kidney. We determined protein level of copper transporters, chaperones, and cuproenzymes including cytochrome c oxidase, as well as antioxidant enzymes function in the kidneys of male Wistar rats subjected to 20% liquid fructose supplementation and/or chronic stress.

Half of expectant women in Montenegro show iodine deficiency, indicating that supplementation during pregnancy is necessary.

Objective: In this study, iodine level in pregnant women of Montenegro and their needs for supplementation were investigated.

Methods: A urinary iodine concentration (UIC) study of 326 pregnant women between September and December 2017 in three regions of Montenegro was performed. UIC was related to creatinine (UI/Cr ratio).

Ibogaine Has Sex-Specific Plasma Bioavailability, Histopathological and Redox/Antioxidant Effects in Rat Liver and Kidneys: A Study on Females.

Ibogaine induces rapid changes in cellular energetics followed by the elevation of antioxidant activities. As shown earlier in male rats, ibogaine treatment with both 1 and 20 mg/kg b.w.

Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and K Channels Mediated.

Ibogaine effects are mediated by cellular receptors, ATP depletion followed by ROS production and antioxidant enzyme activity elevation in a dose and time dependent manner. Since the role of K channels and β-adrenoceptors in ROS cellular circuit was established here we explored their role in ibogaine pro-antioxidant effectiveness. Single dose of ibogaine (10 mg/L i.

Fructose-Rich Diet Attenuates Stress-Induced Metabolic Disturbances in the Liver of Adult Female Rats.

Background: Both fructose consumption and chronic stress contribute to the development of metabolic disorders. The consequences of such combination are not fully understood.

Objective: We investigated whether fructose supplementation and chronic stress synergistically disturb hepatic lipid and glucose metabolism.

Effects of several atypical antipsychotics closapine, sertindole or ziprasidone on hepatic antioxidant enzymes: Possible role in drug-induced liver dysfunction.

Chronic use of atypical antipsychotics may produce hepatic damage. Atypical antipsychotics, including clozapine, sertindole, and ziprasidone, are extensively metabolized by the liver and this process generates toxic-free radical metabolic intermediates which may contribute to liver damage. The aim of this study was to investigate whether clozapine, sertindole, or ziprasidone affected hepatic antioxidant defense enzymes which consequently led to disturbed redox homeostasis.

Fructose Consumption Affects Glucocorticoid Signaling in the Liver of Young Female Rats.

The effects of early-life fructose consumption on hepatic signaling pathways and their relation to the development of metabolic disorders in later life are not fully understood. To investigate whether fructose overconsumption at a young age induces alterations in glucocorticoid signaling that might contribute to development of metabolic disturbances, we analysed glucocorticoid receptor hormone-binding parameters and expression of its target genes involved in gluconeogenesis (phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) and lipid metabolism (lipin-1), as well as redox and inflammatory status in the liver of female rats subjected to a fructose-rich diet immediately after weaning. The fructose diet increased hepatic corticosterone concentration, 11β-hydroxysteroid dehydrogenase type 1 level, glucocorticoid receptor protein level and hormone-binding activity, as well as lipin-1 level.

Edaravone May Prevent Ferroptosis in ALS.

Radicava™ (Edaravone) was approved the Food and Drug Administration (FDA) as a new treatment for amyotrophic lateral sclerosis (ALS). Edaravone is a synthetic antioxidant that specifically targets oxidative damage interacting with lipid radicals in the cell. In ALS disease the multiple cell types are involved in devastating loss of motor neurons.

Opposite clozapine and ziprasidone effects on the reactivity of plasma albumin SH-group are the consequence of their different binding properties dependent on protein fatty acids content.

Antipsychotic drugs interfere with the antioxidant defense system provoking complex and often toxicological effects. Here we examined differences in plasma albumin reduced free thiol (SH) group content and its reactivity as a consequence of clozapine (CLZ) and ziprasidone (ZIP) binding. Chronic administration of CLZ reduced, whereas treatment with ZIP increased albumin-SH content in rats.

Association between neurological soft signs and antioxidant enzyme activity in schizophrenic patients.

To determine the relationship between alterations in the activity of the enzymes participating in antioxidative defense system and neurological soft signs (NSS) in schizophrenic patients with the first episode psychosis (S, n = 19), patients in relapse (S, n = 46), and healthy controls (HC, n = 20). NSS intensity and enzymatic plasma activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were compared between S, S and HC subjects and a follow-up correlation analyses between the enzyme activities and NSS intensity was performed. NSS intensity was increased four times in schizophrenic patients compared with healthy controls.

Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function.

Atypical antipsychotics produce severe side effects including myocarditis that may be attributed to oxidative stress. The aim of this study was to investigate the influence of clozapine, ziprasidone, and sertindole on rat heart morphology and determine whether redox imbalane plays a role in development of histopathological changes. Adult 3-month-old male Wistar rats were treated with recommended daily dose for selected drugs.

The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes.

Ibogaine is an indole alkaloid originally extracted from the root bark of the African rainforest shrub . It has been explored as a treatment for substance abuse because it interrupts drug addiction and relieves withdrawal symptoms. However, it has been shown that ibogaine treatment leads to a sharp and transient fall in cellular ATP level followed by an increase of cellular respiration and ROS production.

Apple pectin-derived oligosaccharides produce carbon dioxide radical anion in Fenton reaction and prevent growth of Escherichia coli and Staphylococcus aureus.

Pectin is the main soluble fiber in apples or citruses. It may be fermented by gut microbiota to metabolites showing local intestinal and systemic effects. A wide range of beneficial effects of dietary pectin includes impacts on the redox milieu and microbiota profile.

Redox properties of transitional milk from mothers of preterm infants.

Aim: There is a discrepancy between the amount of transitional milk produced by mothers of preterm infants and the low capacity of premature infants to consume it. This milk can be used in milk banks, but previous studies found that there are large variations in the level of host-defence proteins in individual samples of milk from mothers of premature infants, which implies that large individual variations in antioxidative defence composition are also possible.

Methods: Milk samples were collected from 20 healthy mothers of preterm infants.

Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney.

The use of atypical antipsychotic drugs (APD) was reported to be associated with adverse effects on the kidneys. Thus, the aim of this study was to examine whether APD exerted their adverse effects by interfering with the renal antioxidant defense system. Male 3-mo-old Wistar rats were treated for 28 d with ziprasidone (ZIP), clozapine (CLO), or sertindole (SER) using a daily dose recommended for antipsychotic drug therapy.

Redox imbalance in peripheral blood of type 1 myotonic dystrophy patients.

Objectives: The aim of our study was to determine if redox imbalance caused by the activities of antioxidant enzymes existed in erythrocytes of type 1 myotonic dystrophy (DM1) patients.

Methods: The activities of erythrocyte superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were measured in 30 DM1 patients and 15 healthy controls (HCs). The obtained values were correlated with the Muscular Impairment Rating Scale (MIRS) score and creatine kinase (CK).

Antioxidative Activity of Colostrum and Human Milk: Effects of Pasteurization and Storage.

Objectives: Milk banks collect, pasteurize, and freeze/store human milk. The processing may alter redox properties of milk, but the effects have not been fully examined.

Methods: We collected 10 mature milk and 10 colostrum samples and applied a battery of biochemical assays and electron paramagnetic resonance spectroscopy to inspect changes that milk undergoes with pasteurization and 30 days storage at -20°C.

Reactions of superoxide dismutases with HS(-)/H2S and superoxide radical anion: An in vitro EPR study.

Interactions of hydrogen sulfide (HS(-)/H2S), a reducing signaling species, with superoxide dimutases (SOD) are poorly understood. We applied low-T EPR spectroscopy to examine the effects of HS(-)/H2S and superoxide radical anion O2.- on metallocenters of FeSOD, MnSOD, and CuZnSOD.