Atranorin (ATR) is a secondary metabolite of lichens. While previous studies investigated the effects of this substance predominantly in an in vitro environment, in our study we investigated the basic physicochemical properties, the binding affinity to human serum albumin (HSA), basic pharmacokinetics, and, mainly, on the systematic effects of ATR in vivo. Sporadic studies describe its effects during, predominantly, cancer. This project is original in terms of testing the efficacy of ATR on a healthy organism, where we can possibly attribute negative effects directly to ATR and not to the disease. For the experiment, 24 Sprague Dawley rats (Velaz, Únetice, Czech Republic) were used. The animals were divided into four groups. The first group (n = 6) included healthy males as control intact rats (♂INT) and the second group (n = 6) included healthy females as control intact rats (♀INT). Groups three and four (♂ATR/n = 6 and ♀ATR/n = 6) consisted of animals with daily administered ATR (10mg/kg body weight) in an ethanol–water solution per os for a one-month period. Our results demonstrate that ATR binds to HSA near the binding site TRP214 and acts on a systemic level. ATR caused mild anemia during the treatment. However, based on the levels of hepatic enzymes in the blood (ALT, ALP, or bilirubin levels), thiobarbituric acid reactive substances (TBARS), or liver histology, no impact on liver was recorded. Significantly increased creatinine and lactate dehydrogenase levels together with increased defecation activity during behavioral testing may indicate the anabolic effect of ATR in skeletal muscles. Interestingly, ATR changed some forms of behavior. ATR at a dose of 10 mg/kg body weight is non-toxic and, therefore, could be used in further research.

Gyrophoric acid (GA), a lichen secondary metabolite, has attracted more attention during the last years because of its potential biological effects. Until now, its effect in vivo has not yet been demonstrated. The aim of our study was to evaluate the basic physicochemical and pharmacokinetic properties of GA, which are directly associated with its biological activities. The stability of the GA in various pH was assessed by conducting repeated UV-VIS spectral measurements. Microsomal stability in rat liver microsomes was performed using Ultra-Performance LC/MS. Binding to human serum albumin (HSA) was assessed using synchronous fluorescence spectra, and molecular docking analysis was used to reveal the binding site of GA to HSA. In the in vivo experiment, 24 Sprague-Dawley rats (Velaz, Únetice, Czech Republic) were used. The animals were divided as follows. The first group (n = 6) included healthy males as control intact rats (♂INT), and the second group (n = 6) included healthy females as controls (♀INT). Groups three and four (♂GA/n = 6 and ♀GA/n = 6) consisted of animals with daily administered GA (10 mg/kg body weight) in an ethanol-water solution per os for a one-month period. We found that GA remained stable under various pH and temperature conditions. It bonded to human serum albumin with the binding constant 1.788 × 10⁶ dm³mol⁻¹ to reach the target tissue via this mechanism. In vivo, GA did not influence body mass gain, food, or fluid intake during the experiment. No liver toxicity was observed. However, GA increased the rearing frequency in behavioral tests (p < 0.01) and center crossings in the elevated plus-maze (p < 0.01 and p < 0.001, respectively). In addition, the time spent in the open arm was prolonged (p < 0.01 and p < 0.001, respectively). Notably, GA was able to pass through the blood–brain barrier, indicating its ability to permeate into the brain and to stimulate neurogenesis in the hilus and subgranular zone of the hippocampus. These observations highlight the potential role of GA in influencing brain function and neurogenesis.

This report describes an adolescent with severe venlafaxine intoxication in whom serial therapeutic drug monitoring (TDM) was performed, enabling detailed toxicokinetic characterization throughout the clinical course. The initial plasma concentration of the active venlafaxine moiety was 7800 ng/mL, nearly 20 times the upper therapeutic reference limit. On admission, the patient presented with tachycardia, bilateral mydriasis, and generalized tonic-clonic seizures, which are typical clinical manifestations of severe venlafaxine intoxication. Due to progressive impairment of consciousness and increasing oxygen requirements, the patient underwent orotracheal intubation and remained on mechanical ventilation for nearly 120 hours. Serial measurements of venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), provided valuable information on the toxicokinetic progression and supported clinical decision-making regarding the timing of extubation. Despite the extremely elevated venlafaxine concentration, cardiotoxicity was limited to transient QTc prolongation without ventricular arrhythmias and moderate elevations of high-sensitivity troponin I (hs-troponin I) and N-terminal pro B-type natriuretic peptide (NT-proBNP). Marked elevations of creatine kinase and myoglobin concentrations were most likely attributable to rhabdomyolysis following general tonic-clonic seizures. TDM demonstrated a progressive increase in the ODV/venlafaxine metabolite-to-parent ratio from 0.30 to 4.50, reflecting the transition from the acute intoxication phase to the elimination phase. The apparent elimination half-life was prolonged to 14.4 hours for venlafaxine and 17.7 hours for ODV. Genotyping revealed the COMT rs4680 Met/Met genotype, which may theoretically influence catecholamine metabolism; however, its contribution to the clinical presentation remains uncertain.

Bile acids (BA) are increasingly recognized as signaling molecules involved in metabolic regulation and inflammatory processes, both of which are relevant to Parkinson’s disease (PD). However, their role in PD and disease progression remains unclear. In this study, plasma BA profiles were analyzed in 113 participants, including early- and advanced-stage PD patients and age- and sex-matched controls, across three time points over three years. Targeted metabolomics using LC-MS was applied to quantify 20 BA, complemented by analyses of functional ratios, including unconjugated/conjugated and hydrophobic/hydrophilic BA ratios and correlation patterns between BA species. Although most individual BA did not show consistent longitudinal changes, pooled analysis identified significant differences in the unconjugated/conjugated BA ratio between PD patients and controls. In contrast, the hydrophobic/hydrophilic ratio did not differ significantly between groups. Correlation analysis revealed differences in selected BA interrelationships, particularly involving primary and secondary BA, while the overall network structure remained largely preserved. These results indicate that BA metabolism in PD might be characterized rather by subtle, distributed alterations than pronounced changes in individual metabolites. BA profiling may therefore contribute to a broader metabolic characterization of PD, but its utility as a standalone biomarker appears limited.

Úvod: Albendazol je stále považovaný za pilier v liečbe alveolárnej echinokokózy (AE). Jeho parazitostatický účinok spolu s variabilnou individuálnou plazmatickou koncentráciou môže byť považovaný za terapeutický problém. Z tohto dôvodu je meranie plazmatickej koncentrácie jeho aktívneho metabolitu albendazol-sulfoxidu dôležitý pri optimalizácii liečby a minimalizácii toxicity. Cieľ: Cieľom štúdie je prezentovať preliminárne dáta zo Slovenska a demonštrovať realizovateľnosť a využiteľnosť stanovenia hladín albendazol--sulfoxidu (ASOX) v klinickej praxi. Metodika: Stanovenie plazmatických koncentrácií ASOX bolo vykonané u 19 pacientov s potvrdenou AE. Dáta boli hodnotené prostredníctvom základnej štatistickej analýzy. Bol realizovaný literárny prehľad podporujúci využiteľnosť monitorovania terapeutických hladín ASOX (TDM). Výsledky: Koncentrácie ASOX sa pohybovali v rozmedzí od 1,18 do 12,10 µmol/ l (priemer 4,11 µmol/ l), pričom niektoré hodnoty prekračovali odporúčaný terapeutický interval. Záver: Naše závery potvrdzujú technickú a klinickú uskutočniteľnosť realizácie TDM pre ASOX a reflektujú krok k personalizovanej liečbe AE na Slovensku.