-
Chemistry (Weinheim An Der Bergstrasse,... Jun 2024Choline chloride (ChCl) based binary and ternary deep eutectic solvents (DES) were evaluated for methylene green electropolymerization with oxalic acid (OA) and ethylene...
Choline chloride (ChCl) based binary and ternary deep eutectic solvents (DES) were evaluated for methylene green electropolymerization with oxalic acid (OA) and ethylene glycol (EG) as hydrogen bond donors. Binary DES ChCl:OA in molar ratios 1:1 and 2:1 and ChCl:EG 1:2 and ternary DES (tDES) in different molar ratios and percentages of water were evaluated. The highest polymer growth was in ChCl:OA:EG-tDES with added water, that had a lower viscosity and higher ionic conductivity when associated with HCl as dopant. This enhanced the formation of more cation radicals and, consequently, more polymer formation. The PMG/MWCNT/GCE-tDES sensor was successfully applied to the simultaneous determination of 5-aminosalicylic acid (5-ASA) and acetaminophen (APAP) by differential pulse voltammetry in the concentration range 2 µM - 200 µM, with detection limits of 0.37 µM and 0.49 µM for 5-ASA and APAP, respectively. The sensor demonstrated good repeatability, reproducibility and stability, and was successfully applied in pharmaceutical formulations.
PubMed: 38900538
DOI: 10.1002/chem.202401752 -
Cureus May 2024With the continued rise of polysubstance use throughout the country, it has been shown to affect a multitude of organ systems. Drug-induced liver injury (DILI) has been...
With the continued rise of polysubstance use throughout the country, it has been shown to affect a multitude of organ systems. Drug-induced liver injury (DILI) has been widely documented in its association with salicylates or acetaminophen and the utility of using N-acetylcysteine (NAC) for its hepatoprotective effects. However, DILI caused by illicit drug use and guideline-directed management has had little research. We present the case of a 29-year-old female who presented with altered mental status. She was found to have a concomitant liver injury and was treated supportively without the use of NAC, with gradual improvement.
PubMed: 38899269
DOI: 10.7759/cureus.60649 -
Mikrochimica Acta Jun 2024The introduced work represents an implementation of the automatic benchtop electrochemical station (BES) as an effective tool for the possibilities of high-throughput...
The introduced work represents an implementation of the automatic benchtop electrochemical station (BES) as an effective tool for the possibilities of high-throughput preparation of modified sensor/biosensors, speeding up the development of the analytical method, and automation of the analytical procedure for the determination of paracetamol (PAR) and dopamine (DOP) as target analytes. Within the preparation of gold nanoparticles modified screen-printed carbon electrode (AuNPs-SPCE) by electrodeposition, the deposition potential E, the deposition time t, and the concentration of HAuCl were optimized and their influence was monitored on 1 mM [Ru(NH)] redox probe and 50 μM DOP. The morphology of the AuNPs-SPCE prepared at various modification conditions was observed by SEM. The analytical performance of the AuNPs-SPCE prepared at different modification conditions was evaluated by a construction of the calibration curves of DOP and PAR. SPCE and AuNPs-SPCE at modification condition providing the best sensitivity to PAR and DOP, were successfully used to determine PAR and DOP in tap water by "spike-recovery" approach. The BES yields better reproducibility of the preparation of AuNPs-SPCE (RSD = 3.0%) in comparison with the case when AuNPs-SPCE was prepared manually by highly skilled laboratory operator (RSD = 7.0%).
Topics: Acetaminophen; Dopamine; Gold; Metal Nanoparticles; Electrochemical Techniques; Electrodes; Biosensing Techniques; Limit of Detection; Carbon
PubMed: 38898321
DOI: 10.1007/s00604-024-06454-6 -
Mikrochimica Acta Jun 2024Amlodipine (AM) is a long active calcium channel blocker used to relax blood vessels by preventing calcium ion transport into the vascular walls and its supporting...
Binder-free and efficient voltammetric sensor based on Zn-CaCuO nanoparticles for simultaneous determination of amlodipine, acetaminophen, and ascorbic acid in hypertension patients.
Amlodipine (AM) is a long active calcium channel blocker used to relax blood vessels by preventing calcium ion transport into the vascular walls and its supporting molecules acetaminophen (AP) and ascorbic acid (AA) are recommended for hypertension control and prevention. Considering their therapeutic importance and potential side effects due to over dosage, we have fabricated a sensor for individual and simultaneous determination of AA, AP, and AM in pharmaceuticals and human urine using novel Zn-doped CaCuO nanoparticles modified glassy carbon electrode (GCE). Optimally doped CaCuO (2.5 wt% Zn at Cu site) enhanced the detection of target molecules over much wider concentration ranges of 50 to 3130 µM for AA, 0.25 to 417 µM for AP, and 0.8 to 354 µM for AM with the corresponding lowest detection limits of 14 µM, 0.05 µM, and 0.07 µM, respectively. Furthermore, the Zn-CaCuO/GCE exhibited excellent selectivity and high sensitivity even in the presence of several potential interfering agents. The usefulness of the developed electrode was tested using an amlodipine besylate tablet and urine samples of seven hypertension patients under medication. The results confirmed the presence of a significant amount of AP and AM in six patients' urine samples indicating that the personalized medication is essential and the quantum of medication need to be fixed by knowing the excess medicines excreted through urine. Thus, the Zn-CaCuO/GCE with a high recovery percentage and good sensitivity shall be useful in the pharmaceutical and biomedical sectors.
Topics: Amlodipine; Humans; Ascorbic Acid; Copper; Acetaminophen; Zinc; Hypertension; Electrodes; Electrochemical Techniques; Limit of Detection; Metal Nanoparticles; Nanoparticles; Carbon
PubMed: 38898141
DOI: 10.1007/s00604-024-06473-3 -
RSC Advances Jun 2024A supramolecular complex μ--tetra(4-pyridyl) porphyrinate nickel(ii)tetrakis[bis(bipyridine)(chloro)ruthenium(ii)] ([NiTPyP{Ru(bipy)Cl}]) was intercalated into the...
Glassy carbon electrode modified with a film of tetraruthenated nickel(ii) porphyrin located in natural smectite clay's interlayer for the simultaneous sensing of dopamine, acetaminophen and tryptophan.
A supramolecular complex μ--tetra(4-pyridyl) porphyrinate nickel(ii)tetrakis[bis(bipyridine)(chloro)ruthenium(ii)] ([NiTPyP{Ru(bipy)Cl}]) was intercalated into the interlayer space of natural smectite clay (shortened as Ba) collected in a Cameroonian deposit at Bagba hill. Physicochemical characterization of the resulting material using ultraviolet-visible spectroscopy (UV-vis), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) confirmed the intercalation of the porphyrin within the interlayer space of the clay. The intercalated clay was then used to form a stable thin film onto a glassy carbon electrode (GCE) by drop casting a suspension of the hybrid material. The GCE modified with the intercalated organoclay endowed the electrode with a larger electrochemically active surface area, good stability, high selectivity, and sensitivity toward dopamine (DA), acetaminophen (AC) and tryptophan (Trp). In addition, it was observed that the modified electrodes exhibited good and pH-dependent electrocatalytic properties toward these analytes. The simultaneous determination of DA, AC and Trp at [NiTPyP{Ru(bipy)Cl}]-Ba/GCE was thus possible without the interference of one analyte on the others, and the resulting calibration curve exhibits two segments for the three analytes. For DA, AC and Trp, the detection limits were found to be 0.8 μM, 0.3 μM and 0.3 μM, respectively. The [NiTPyP{Ru(bipy)Cl}]-Ba/GCE modified electrodes were successfully applied for the determination of AC in Paracetamol, a commercial product, and Trp in real pharmaceutical formulation samples.
PubMed: 38895529
DOI: 10.1039/d4ra03253e -
BioRxiv : the Preprint Server For... Jun 2024Hepatic endothelial cell (EC) dysfunction and centrilobular hepatocyte necrosis occur with acetaminophen (APAP) overdose. The protease thrombin, which is acutely...
BACKGROUND & AIMS
Hepatic endothelial cell (EC) dysfunction and centrilobular hepatocyte necrosis occur with acetaminophen (APAP) overdose. The protease thrombin, which is acutely generated during APAP overdose, can signal through protease-activated receptors 1 and 4 (PAR1/PAR4). PAR1 is a high-affinity thrombin receptor that is known to signal on ECs, whereas PAR4 is a low-affinity thrombin receptor, and evidence for its expression and function on ECs is mixed. This study aims to exploit the high levels of thrombin generated during APAP overdose to determine (1) if hepatic endothelial PAR4 is a functional receptor, and (2) endothelial-specific functions for PAR1 and PAR4 in a high thrombin setting.
METHODS
We generated mice with conditional deletion(s) of in ECs and overdosed them with APAP. Hepatic vascular permeability, erythrocyte congestion/bleeding, and liver function were assessed following overdose. Additionally, we investigated the expression levels of endothelial PARs and how they influence transcription in APAP-overdosed liver ECs using endothelial Translating Ribosome Affinity Purification followed by next-generation sequencing (TRAPseq).
RESULTS
We found that mice deficient in high-expressing endothelial or low-expressing had equivalent reductions in APAP-induced hepatic vascular instability but no effect on hepatocyte necrosis. Additionally, mice with loss of endothelial and had reduced permeability at an earlier time point after APAP overdose when compared to mice singly deficient in either receptor in ECs. We also found that endothelial PAR1-but not PAR4-can regulate transcription in hepatic ECs.
CONCLUSIONS
Low-expressing PAR4 can react similarly to high-expressing PAR1 in APAP-overdosed hepatic ECs, demonstrating that PAR4 is a potent thrombin receptor. Additionally, these receptors are functionally redundant but act divergently in their expression and ability to influence transcription in hepatic ECs.
PubMed: 38895465
DOI: 10.1101/2024.06.07.598028 -
International Journal of Molecular... Jun 2024Acute liver failure is an infrequent yet fatal condition marked by rapid liver function decline, leading to abnormalities in blood clotting and cognitive impairment...
Acute liver failure is an infrequent yet fatal condition marked by rapid liver function decline, leading to abnormalities in blood clotting and cognitive impairment among individuals without prior liver ailments. The primary reasons for liver failure are infection with hepatitis virus or overdose of certain medicines, such as acetaminophen. (PT), a type of microalgae known as a diatom species, has been reported to contain an active ingredient with anti-inflammatory and anti-obesity effects. In this study, we evaluated the preventive and therapeutic activities of PT extract in acute liver failure. To achieve our purpose, we used two different acute liver failure models: acetaminophen- and D-GalN/LPS-induced acute liver failure. PT extract showed protective activity against acetaminophen-induced acute liver failure through attenuation of the inflammatory response. However, we failed to demonstrate the protective effects of PT against acute liver injury in the D-GalN/LPS model. Although the PT extract did not show protective activity against two different acute liver failure animal models, this study clearly demonstrates the importance of considering the differences among animal models when selecting an acute liver failure model for evaluation.
Topics: Animals; Acetaminophen; Mice; Chemical and Drug Induced Liver Injury; Microalgae; Disease Models, Animal; Liver Failure, Acute; Male; Protective Agents; Ethanol; Diatoms; Liver; Lipopolysaccharides
PubMed: 38892435
DOI: 10.3390/ijms25116247 -
International Journal of Molecular... May 2024Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis...
Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis currently requires blood collection 24-72 h after APAP ingestion, necessitating repeated tests and hospitalization. Here, we assessed earlier ALF diagnosis using positron emission tomography (PET) imaging of translocator proteins (TSPOs), which are involved in molecular transport, oxidative stress, apoptosis, and energy metabolism, with the radiotracer [F]GE180. We intraperitoneally administered propacetamol hydrochloride to male C57BL/6 mice to induce ALF. We performed in vivo PET/CT imaging 3 h later using the TSPO-specific radiotracer [F]GE180 and quantitatively analyzed the PET images by determining the averaged standardized uptake value (SUV) in the liver parenchyma. We assessed liver TSPO expression levels via real-time polymerase chain reaction, Western blotting, and immunohistochemistry. [F]GE180 PET imaging 3 h after propacetamol administration (1500 mg/kg) significantly increased liver SUV compared to controls ( = 0.001). Analyses showed a 10-fold and 4-fold increase in TSPO gene and protein expression, respectively, in the liver, 3 h after propacetamol induction compared to controls. [F]GE180 PET visualized and quantified propacetamol-induced ALF through TSPO overexpression. These findings highlight TSPO PET's potential as a non-invasive imaging biomarker for early-stage ALF.
Topics: Animals; Liver Failure, Acute; Acetaminophen; Male; Mice; Mice, Inbred C57BL; Receptors, GABA; Positron-Emission Tomography; Liver; Positron Emission Tomography Computed Tomography; Fluorine Radioisotopes; Radiopharmaceuticals; Disease Models, Animal; Carbazoles
PubMed: 38892130
DOI: 10.3390/ijms25115942 -
Cell Communication and Signaling : CCS Jun 2024Balloon flower root-derived exosome-like nanoparticles (BDEs) have recently been proposed as physiologically active molecules with no cytotoxicity. However, the...
A novel approach to alleviate acetaminophen-induced hepatotoxicity with hybrid balloon flower root-derived exosome-like nanoparticles (BDEs) with silymarin via inhibition of hepatocyte MAPK pathway and apoptosis.
INTRODUCTION
Balloon flower root-derived exosome-like nanoparticles (BDEs) have recently been proposed as physiologically active molecules with no cytotoxicity. However, the therapeutic effects of drug-induced hepatotoxicity of BDEs have not been elucidated. BDEs contain a large amount of platycodin D, which is widely known to be effective in regulating inflammation and ameliorating systemic toxicity. Thus, the main therapeutic activity of BDEs is attributed to inhibiting the inflammatory response and alleviating toxicity. In this study, we fabricated the hybrid BDEs fused with liposomes containing silymarin (SM) to enhance the synergistic effect on inhibition of acetaminophen-induced hepatotoxicity (APAP).
OBJECTIVE
Considering the potential therapeutic effects of BDEs, and the potential to achieve synergistic effects to improve therapeutic outcomes, we constructed hybrid BDEs with a soy lecithin-based liposome loaded with SM. Since liposomes can provide higher thermal stability and have greater structural integrity, these might be more resistant to clearance and enzymatic degradation of drug molecules.
METHODS
Hybrid BDEs with liposome-loaded SM (BDEs@lipo-SM) were fabricated by thin-film hydration and extrusion. BDEs@lipo-SM were characterized using dynamic light scattering and high-performance liquid chromatography. After confirmation of the physical properties of BDEs@lipo-SM, various therapeutic properties were evaluated.
RESULTS
BDEs@lipo-SM were internalized by hepatocytes and immune cells and significantly decreased mRNA expression of apoptosis and inflammation-relevant cytokines by inhibiting the hepatocyte MAPK pathway. BDEs@lipo-SM significantly induced an increase in glutathione levels and inhibited APAP-induced hepatotoxicity.
CONCLUSION
From this study, we know that BDEs are reliable and safe nanovesicles containing natural metabolites derived from balloon flower, and they can facilitate intercellular communication. BDEs are also easily modified to enhance drug loading capacity, targeting effects, and long-term accumulation in vivo. BDEs@lipo-SM have therapeutic benefits for acute liver injury and can alleviate cell death and toxicity. They can be efficiently delivered to the liver and effectively inhibit APAP-induced hepatotoxicity by inhibiting the MAPK signaling pathway and apoptosis, which accelerates liver recovery in the APAP-induced acute liver injury model. These findings highlight that BDEs represent an attractive delivery vehicle for drug delivery.
Topics: Acetaminophen; Apoptosis; Animals; Nanoparticles; Exosomes; Hepatocytes; Silymarin; MAP Kinase Signaling System; Mice; Chemical and Drug Induced Liver Injury; Humans; Liposomes; Male; Plant Roots; Mice, Inbred C57BL
PubMed: 38890646
DOI: 10.1186/s12964-024-01700-z -
AAPS PharmSciTech Jun 2024Unexpected cross-contamination by foreign components during the manufacturing and quality control of pharmaceutical products poses a serious threat to the stable supply...
Unexpected cross-contamination by foreign components during the manufacturing and quality control of pharmaceutical products poses a serious threat to the stable supply of drugs and the safety of customers. In Japan, in 2020, a mix-up containing a sleeping drug went undetected by liquid chromatography during the final quality test because the test focused only on the main active pharmaceutical ingredient (API) and known impurities. In this study, we assessed the ability of a powder rheometer to analyze powder characteristics in detail to determine whether it can detect the influence of foreign APIs on powder flow. Aspirin, which was used as the host API, was combined with the guest APIs (acetaminophen from two manufacturers and albumin tannate) and subsequently subjected to shear and stability tests. The influence of known lubricants (magnesium stearate and leucine) on powder flow was also evaluated for standardized comparison. Using microscopic morphological analysis, the surface of the powder was observed to confirm physical interactions between the host and guest APIs. In most cases, the guest APIs were statistically detected due to characteristics such as their powder diameter, pre-milling, and cohesion properties. Furthermore, we evaluated the flowability of a formulation incorporating guest APIs for direct compression method along with additives such as microcrystalline cellulose, potato starch, and lactose. Even in the presence of several additives, the influence of the added guest APIs was successfully detected. In conclusion, powder rheometry is a promising method for ensuring stable product quality and reducing the risk of unforeseen cross-contamination by foreign APIs.
Topics: Powders; Rheology; Drug Contamination; Excipients; Acetaminophen; Cellulose; Pharmaceutical Preparations; Quality Control; Aspirin; Chemistry, Pharmaceutical; Lactose; Drug Compounding; Lubricants; Bulk Drugs
PubMed: 38890193
DOI: 10.1208/s12249-024-02856-0