Bożena Bukowska

Ethanol consumption can modify both drug exposure and drug response. However, the clinical relevance of these interactions depends strongly on the timing and pattern of alcohol intake, the affected pharmacological pathway, the dosage form and organ reserve. This review summarizes current evidence on ethanol–drug interactions, particularly human crossover studies, phenotyping studies, cohort analyses and appropriate case reports. It distinguishes acute ethanol–drug co-exposure, chronic alcohol exposure, drug use during early abstinence after chronic drinking, and pharmacotherapy in alcohol-associated liver disease. Key mechanisms include ADH- and ALDH-dependent ethanol oxidation, acetaldehyde formation, NADH/NAD⁺ redox shift, CYP2E1 induction, carboxylesterase 1 (CES1) modulation, altered intestinal and hepatic first-pass handling, dose dumping from susceptible modified-release products, changes in protein binding in alcohol-associated liver disease, and ALDH inhibition with acetaldehyde accumulation in disulfiram-like reactions. At the molecular level, ethanol may promote acetaldehyde adduct formation with proteins and DNA, CYP2E1-driven reactive oxygen species generation, redox stress, intestinal barrier injury, and CES1-dependent transesterification of selected ester drugs. Acute ethanol intake mainly increases pharmacodynamic toxicity and causes short-term pharmacokinetic disturbances, including enhanced central nervous system depression, delayed gastric emptying, impaired glucose and lactate handling and altered hemodynamic responses. In contrast, chronic exposure, early abstinence and alcohol-associated liver disease are more often associated with hepatic enzyme and transporter remodeling, altered protein binding, reduced hepatic or renal reserve, and greater susceptibility to drug-related organ injury. The highest-risk scenarios involve older adults, polypharmacy, alcohol-associated liver disease, dehydration or acute illness, early abstinence, and the concurrent use of central nervous system depressants, glucose-lowering drugs, NSAIDs, antihypertensives, renally eliminated drugs or warfarin. Hence, ethanol exposure should be treated as a dynamic, context-dependent modifier factor that can acutely exacerbate pharmacodynamic toxicity, alter selected pharmacokinetic pathways and lower organ tolerance to drug-related injury.

The widespread presence of polystyrene nanoparticles (PS-NPs) in the human body has raised concerns about their potential biological toxicity. When assessing the safety of nanoparticles and other xenobiotics, a key aspect is their effect on blood cells, particularly erythrocytes, which experience the most direct exposure to nanoparticles circulating in the bloodstream. The present study evaluated the impact of non-functionalized PS-NPs with diameters of ∼30 nm, ∼45 nm, and ∼70 nm on human red blood cells after 24 hours of incubation. The studied PS-NPs did not influence intracellular Ca²⁺ ion levels or caspase 3 activity, and did not induce phosphatidylserine translocation at pre-hemolytic concentrations (below 100 µg/mL). Moreover, exposure did not increase intracellular ROS levels at any of the tested concentrations, suggesting that generalized intracellular oxidative stress is likely not the primary mechanism underlying the effects induced by PS-NPs in human erythrocytes. However, the observed increase in lipid peroxidation, detected from 50 µg/ml, indicates that oxidative damage at the membrane level may contribute to the overall toxic response. The results suggest that PS-NPs interact primarily with the erythrocyte membrane, leading to membrane destabilization associated with increased calpain activity, observed already at a concentration of 1 µg/mL, and enhanced lipid peroxidation. It is noteworthy that the most pronounced changes were induced by the smallest nanoparticles (∼30 nm), suggesting a size-dependent effect on erythrocyte integrity. These findings suggest that PS-NP toxicity in erythrocytes is mediated mainly through red blood cell membrane destabilization rather than classical intracellular oxidative stress alone.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as alirocumab and evolocumab, effectively reduce LDL‐C levels, improve cardiovascular outcomes, and are well tolerated in the treatment of heterozygous familial hypercholesterolemia (HeFH). Oxidative stress, increased in HeFH, leads to DNA damage, LDL oxidation (ox‐LDL), and reduced total plasma antioxidant capacity, which promotes the development of atherosclerosis. The aim of the study was to assess whether treatment with PCSK9 inhibitors reduces ox‐LDL, anti‐ox‐LDL antibodies, oxidative stress, and DNA damage, including 8‐OH‐Gua levels. The study included 40 patients with HeFH diagnosed clinically or genetically, and 33 healthy volunteers at low cardiovascular risk as controls. Blood samples were collected from all participants for lipid profile, Lp(a), oxidative stress markers (ox‐LDL, 8‐OHdG, anti‐oxLDL antibodies), total antioxidant capacity of plasma (TAC), and DNA damage status (using the comet assay with repair enzymes). The study showed that treatment with PCSK9 inhibitors (alirocumab or evolocumab) in HeFH patients significantly improved lipid profiles and reduced levels of oxidative stress markers such as 8‐OHdG and ox‐LDL, while increasing levels of anti‐ox‐LDL and TAC. This therapy also significantly reduced purine and pyrimidine DNA damage, although not to the level observed in the control group. The efficacy of reducing DNA damage was greater with alirocumab, which could be related to higher baseline levels of Lp(a) and oxidative damage in these patients. Treatment with PCSK9 inhibitors in HeFH patients reduces oxidative stress and DNA damage, indicating additional non‐lipid benefits that support their use in preventing atherosclerotic complications.

The growing interest in functional beer production has led to the exploration of unconventional raw materials, such as hemp (Cannabis sativa L.), for brewing applications. This study aimed to evaluate the volatile organic compound (VOC) profile and the macro- and microelement composition of barley wort enriched with varying proportions (10% and 30%) of malted and unmalted hemp seeds, using solid-phase microextraction followed by gas chromatography–mass spectrometry (SPME–GC–MS) and atomic absorption spectrometry (AAS). A total of 64 VOCs were identified across four wort variants: control (barley malt only), 10% malted hemp, 30% malted hemp, and 30% unmalted hemp. The aroma profile was significantly influenced by compounds such as 2,3-butanediol, 1-hexanol, 3-methyl-1-butanol, 3-hydroxy-2-butanone, hexanoic acid, and 4-vinylguaiacol (p < 0.001). Principal component analysis (PCA) revealed clear separation between wort types based on the relative abundance of alcohols, acids, ketones, and phenols, indicating a progressive shift from sweet/malty toward acidic, green, and herbal aroma notes as hemp addition increased. Notably, unmalted hemp seeds resulted in a pronounced dominance of hexanoic acid, which may contribute to earthy and rancid sensory attributes. The evaluation of selected mineral elements showed that the key macroelements differentiating the worts were potassium, magnesium, phosphorus, and calcium, while among the microelements the distinguishing elements were manganese, iron, and sodium. These findings demonstrate the strong modulating effect of aromatic hemp-derived materials on the aroma composition and selected mineral content of brewing worts, supporting their targeted use in novel beer formulations.

Heterozygous familial hypercholesterolemia (HeFH) is a common autosomal dominant genetic disease (1:250) characterized by elevated LDL-C. Patients with HeFH are at increased risk of premature atherosclerosis and have at least a 10-fold greater chance of cardiovascular disease (CVD). The present study examines the effect of PCSK9 inhibitor treatment (iPCSK9: arilocumab or evolocumab) on DNA damage in HeFH patients. Fifty-six patients were studied, with a normolipidemic group (control; n = 20) and patients with HeFH (study group; n = 36). DNA damage was determined by alkaline comet assay and PCSK9 protein level by ELISA. PCSK9i treatment was found to be associated with lower DNA damage, Lp(a), PCSK9, and lipid profile compared to before treatment. However, 16 of 36 patients still had Lp(a) values above 125 nmol/L, and reduced Lp(a) did not correlate with reduced DNA damage. Reduced PCSK9 demonstrated a moderately positive correlation (r = 0.48) with reduced DNA damage. PCSK9i therapy reduces the level of DNA damage in HeFH patients, regardless of the type of inhibitor. While our findings confirm that PCSK9 treatment can reduce DNA damage, the mechanism remains unclear.

This study examined the profile of bioactive peptides and polysaccharides in beer wort enriched with malted and unmalted hemp seeds. The aim of this research was to evaluate the influence of different hemp processing methods (malted versus unmalted) on the concentration and characteristics of bioactive compounds—specifically (1) peptides exhibiting antioxidant, anti-inflammatory, and antihypertensive activities and (2) soluble polysaccharide fractions that affect wort viscosity and prebiotic potential. The results indicated that supplementation with 10% malted hemp seeds was most favorable. This level of addition enhanced the peptide composition of the wort without adversely affecting fermentation efficiency. Moreover, it facilitated the generation of functional peptides with antioxidant and flavor-enhancing properties and introduced non-fermentable polysaccharides that improved wort viscosity and foam stability without the negative effects observed at higher hemp seed concentrations. In contrast, a 30% addition of hemp seeds, particularly in unmalted form, led to a reduction in fermentable sugar and peptide contents and increased the likelihood of fermentation slowdown. The incorporation of 10% malted hemp seeds has the potential to enhance the sensory and functional attributes of beer, primarily due to the presence of bioactive peptides and polysaccharides, while maintaining fermentation performance and clarity. Fermentation and brewing efficiency may decline at higher hemp seed inclusion rates, warranting further investigation. The use of unmalted hemp necessitates enzymatic treatment to improve fermentable sugar availability. Additionally, high-performance size-exclusion chromatography (HPSEC) proved to be a valuable analytical tool for optimizing wort composition in the development of hemp-enriched beers.

The aim of the study was to determine the concentration- and size-dependent effects of ~30 nm, ~45 nm and ~70 nm non-functionalized polystyrene nanoparticles (PS-NPs) on human serum albumin (HSA) and human erythrocyte proteins in vitro. . HSA or human erythrocytes were exposed to PS-NPs at concentrations ranging from 0.001 to 100 µg/mL for 24 h. Any resulting changes in HSA secondary structure were investigated using circular dichroism (CD), fluorescence spectrum analysis, and fluorescence lifetime measurements. Incubation with 50 µg/mL and 100 µg/mL PS-NPs resulted in an increase in the hydrodynamic diameter of PS-NPs and caused significant alterations in HSA secondary structure for all tested nanoparticle sizes. Additionally, treatment with the ~30 nm and ~45 nm PS-NPs resulted in a more intense HSA fluorescence signal and changes in mean fluorescence lifetimes, indicating interactions between PS-NPs and HSA. Incubation with PS-NPs (0.1-1 µg/mL) also led to significant changes in relative viscosity and increased protein carbonyl content in erythrocytes (10-100 µg/mL); however, no significant changes in acetylcholinesterase (AChE) activity or methemoglobin levels were observed. The study confirms that non-functionalized polystyrene nanoparticles influence the structure and functional properties of human plasma and erythrocyte proteins under in vitro conditions, and their effects are clearly dependent on the size and concentration of the nanoparticles. It is likely that PS-NPs can modify the structure of albumin, which may indirectly potentiate plastic-related damage to erythrocytes in vivo. The potential influence of albumin modified by plastic particles on the properties of human erythrocytes in vivo was discussed.

: Early studies have shown that erythrocytes have caspase-3 and caspase-8 and are capable of dying through an apoptotic-like cell death triggered by Ca²⁺ ionophores. This cell death is associated with apoptosis-like morphological signs, including cell shrinkage, membrane blebbing, and phosphatidylserine externalization. To emphasize that mature erythrocytes don’t have the apoptotic mitochondrial machinery and distinguish this unique cell death modality from apoptosis, it was named “eryptosis”. Over recent decades, our knowledge of eryptosis has been significantly expanded, providing more insights into the uniqueness of cell death pathways in erythrocytes. In this review, we aim to summarize our current understanding of eryptosis, formulate the nomenclature and guidelines to interpret results of eryptosis studies, provide a synopsis of morphological and biochemical features of eryptosis, and highlight the role of eryptosis in health and disease, including its druggability.

Food components and herbal substances can inhibit or enhance the therapeutic effects of drugs, thus influencing their efficacy and safety. As relatively little in known of these interactions, the aim of this review is to shed further light on the potentially dangerous influences that food and herbs may have on cytochrome P450 enzyme (CYP) and monoamine oxidase (MAO) activity in the first stage of drug biotransformation. The review includes documented cases in which such interactions have led to health complications in patients. For example, fruit juices, such as grapefruit juice, cranberry juice, and pomegranate juice, have been found to interact with drugs, and to particularly inhibit CYP450 activity, and commonly used herbs are known to inhibit (e.g., Astragalus membranous) or induce (e.g., Hypericum perforatum) CYP enzymes involved in drug metabolism. CYP is also induced by polycyclic aromatic hydrocarbons (PAHs), found in grilled meat and tobacco smoke. The paper also discusses the toxic effects of tyramine, present in inter alia blue cheese, resulting from interactions with MAO-metabolised drugs. Most importantly, while the quantity of food and herbs consumed plays a significant role in the described drug interactions, it is possible for toxic effects to be observed even after the consumption of relatively small amounts. Patients are encouraged to consult a healthcare provider about any potential drug interactions that may occur when starting a new medication.