Non-steroidal Anti-inflammatory Ibuprofen Research Articles

Janus Dendrimers as Nanocarriers of Ibuprofen, Chlorambucil and Their Anticancer Activity.

Janus Dendrimer represents a novel class of synthetic nanocarriers. Since it is possible to introduce multiple drugs and target moieties, this helps the designing of new biocompatible forms with pharmacological activities comprised of different drugs with tailor-made functionalities, such as anticancer and nonsteroidal anti-inflammatory, which could improve the anticancer activity with less toxicity. This study aimed to determine the anticancer activity of the Janus dendrimers formed by two dendrons. One dendron conjugates with chlorambucil, and the other dendron conjugates with Ibuprofen. The cytotoxicity of the drug carriers was determined by the sulforhodamine B (SRB) assay for three cell lines. PC-3 (human prostatic adenocarcinoma), HCT-15 (human colorectal adenocarcinoma), MFC-7 (human breast cancer) and the COS-7 African green monkey kidney (used as a control) cell lines were seeded into 96-well plates at a density of 5x103 cells/well and cultured for 24 h before use. All the obtained compounds were characterized by 1H and 13C NMR one and two dimensions, UV-vis, FTIR, MALDI-TOF, Electrospray mass, and FAB+. Microscopic images were taken in an Inverted microscope Nikon, Diaphot 300, 10x4 in culture medium. Janus dendrimers (G1 and G2) were synthesized via an azide-alkyne click-chemistry reaction attaching on one face dendrons with ibuprofen molecules and, on the other face, attached a chlorambucil-derivative. The IC50 behavior of the conjugates of the first and second generations showed anticancer activity against PC-3, HCT-15, and MFC-7 cell lines. The second generation was more active against PC-3, HCT-15 and MFC-7 with IC50 of 3.8±0.5, 3.0±0.2 and 3.7±1.1 M, respectively Conclusion: The new Janus dendrimers with anticancer chlorambucil and nonsteroidal anti-inflammatory Ibuprofen can improve the anticancer activity of chlorambucil with less toxicity.

Effects of Ibuprofen and Diclofenac Pre-Treatment on Viability and Apoptosis Processes in Human Dental Pulp Stem Cells.

Background and Objectives: Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation, often complicated by pain, which is managed by using nonsteroidal anti-inflammatory drugs (NSAIDs). However, information is limited about how NSAIDs affect the therapeutic potential of stem cells. Materials and Methods: We investigated the effects of ibuprofen and diclofenac on the characteristics, morphology, and immunophenotype of human mesenchymal stromal cells isolated from the dental pulp (DPSCs) and cultured in vitro, as well as their effects on the expression of angiogenic growth factors (VEGFA and HGF) and selected genes in apoptosis signalling pathways (BAX, BAK, CASP3, CASP9, and BCL2). Results: Ibuprofen and diclofenac significantly reduced the viability of DPSCs, while the expression of mesenchymal stem cell surface markers was unaffected. Both ibuprofen and diclofenac treatment significantly upregulated the expression of HGF, while the expression of VEGFA remained unchanged. Ibuprofen significantly altered the expression of several apoptosis-related genes, including the upregulation of CASP9 and BCL2, with decreased CASP3 expression. BAK, CASP3, CASP9, and BCL2 expressions were significantly increased in the diclofenac-treated DPSCs, while no difference was demonstrated in BAX expression. Conclusions: Our results suggest that concomitant use of the NSAIDs ibuprofen or diclofenac with stem cell therapy may negatively impact cell viability and alter the expression of apoptosis-related genes, affecting the efficacy of stem cell therapy.

Design, synthesis, and antitumor mechanism investigation of iridium(III) complexes conjugated with ibuprofen

The design and synthesis of a series of metal complexes formed by non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen (IBP) and iridium(III), with the molecular formula [Ir(C^N)2bpy(4-CH2OIBP-4’-CH2OIBP)](PF6) (Ir-IBP-1, Ir-IBP-2) (C^N = 2-phenylpyridine (ppy, Ir-IBP-1), 2-(2-thienyl)pyridine (thpy, Ir-IBP-2)) was introduced in this article. Firstly, it was found that the anti-proliferative activity of these complexes was more effective than that of cisplatin. Further research showed that Ir-IBP-1 and Ir-IBP-2 can accumulate in intracellular mitochondria, thereby disrupting mitochondrial membrane potential (MMP), increasing intracellular reactive oxygen species (ROS), blocking the G2/M phase of the cell cycle, and inducing cell apoptosis. In terms of protein expression, the expression of COX-2, MMP-9, NLRP3 and Caspase-1 proteins can be downregulated, indicating their ability to anti-inflammatory and overcome immune evasion. Furthermore, Ir-IBP-1 and Ir-IBP-2 can induce immunogenic cell death (ICD) by triggering the release of cell surface calreticulin (CRT), high mobility group box 1 (HMGB1) and adenosine triphosphate (ATP). Overall, iridium(III)-IBP conjugates exhibit various anti-tumor mechanisms, including mitochondrial damage, cell cycle arrest, inflammatory suppression, and induction of ICD.

Ibuprofen: A multi-purpose active pharmaceutical ingredient as versatile ligand for zinc(II) and copper(II). Solid state and solution studies

Two new, Zn(II) and Cu(II), complexes of the non-steroidal anti inflammatory drug (NSAID) ibuprofen (HIbu) are reported. Results from their solid state investigation are complemented by potentiometric and 1H NMR studies in view of the role that chelation of these biologically relevant metal ions might play in affecting the Active Pharmaceutical Ingredient (API) biological properties, but also of the use of metallo-ibuprofen drugs. In the solid state, the ibuprofenate anion (Ibu−) gives rise to 0- and 1-D species, [Zn(Ibu)2(H2O)2] and [Cu(Ibu)2]n, respectively. The [Zn(Ibu)2] species is also present in H2O/EtOH 50 % v/v solution (pKw = 14.41(1)) and starting from pH 4–4.5 coexists in solution with the [Zn(Ibu)]+ one. As for the copper structure, it represents, to the best of our knowledge, the first example of 1-D coordination polymer consisting of copper-ibuprofen dinuclear paddle-wheel units. Interestingly, this crystal phase is the only one obtained irrespective of the different synthetic and crystallization procedures adopted. Potentiometric titrations evidence that copper(II) gives the more stable complexes (also in this case [Cu(Ibu)2] and[Cu(Ibu)]+ coexist in solution) with respect to the zinc ones. Lastly, in light of the increasing interest around the antibacterial activities of NSAIDs and NSAIDs-containing compounds, the antimicrobial effects of ibuprofen, [Zn(Ibu)2(H2O)2] and [Cu(Ibu)2]n were preliminary evaluateted on Bacillus Subtilis, chosen as a model of Gram-positive bacteria.

Hereditary periodic fevers in children

Fevers in children is a pressing challenge in paediatrics, as they are one of the most common symptoms people seek medical help. Autoinflammatory diseases (AIDs) constitute a group of diseases, where fever is one of the main symptoms, and fever attacks have a certain frequency and duration. Autoinflammatory diseases are rooted in the systemic aseptic inflammation associated with activation of the innate immune system, without elevated levels of autoantibodies. The most common autoinflammatory diseases include hereditary periodic fevers, among which are familial Mediterranean fever (FMF), HIDS/MKD, CAPS-, TRAPS-syndromes and rarer diseases (deficiency of natural interleukin receptor antagonists). The pathogenesis of this group of diseases is based on the process of accelerated formation of a supramolecular protein complex (inflammasome), which subsequently leads to the transition of the inactive form of IL1β into its active form. The clinical presentations of these diseases may be similar and include episodes of fever, abdominal pain, arthralgia, various rashes, etc., as well as an increase in acute phase parameters. These diseases are characterized by symptoms at certain intervals; they usually have intervals without showing any symptoms. Familial Mediterranean fever is characterized by a certain ethnic background (Armenians, Turks, Arabs, Jews). Today, molecular genetic testing is the most accurate method for diagnosing familial Mediterranean fever. Current therapy aims to prevent attacks of the disease, but it is also important to use symptomatic therapy to relieve the child’s condition when an attack has already developed. Modern treatment strategies include both drugs that have long been used in paediatric practice (colchicine, non-steroidal anti-inflammatory drugs (ibuprofen), glucocorticosteroids) and novel genetically engineered biological drugs (interleukin antagonists and tumour necrosis factor inhibitors, etc.).

Long-term dietary exposure to the non-steroidal anti-inflammatory drugs diclofenac and ibuprofen can affect the physiology of common carp (Cyprinus carpio) on multiple levels, even at “environmentally relevant” concentrations

The aim of the study was to evaluate the effects of emerging environmental contaminants, the non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac (DCF) and ibuprofen (IBP), on physiological functions in juvenile common carp (Cyprinus carpio). Fish were exposed for 6 weeks, and for the first time, NSAIDs were administered through diet. Either substance was tested at two concentrations, 20 or 2000 μg/kg, resulting in four different treatments (DCF 20, DCF 2000, IBP 20, IBP 2000). The effects on haematological and biochemical profiles, the biomarkers of oxidative stress, and endocrine disruption were studied, and changes in RNA transcription were also monitored to obtain a comprehensive picture of toxicity. Fish exposure to high concentrations of NSAIDs (DCF 2000, IBP 2000) elicited numerous statistically significant changes (p < 0.05) in the endpoints investigated, with DCF being almost always more efficient than IBP. Compared to control fish, a decrease in total leukocyte count attributed to relative lymphopenia was observed. Plasma concentrations of total proteins, ammonia, and thyroxine, and enzyme activities of alanine aminotransferase (ALT), aspartate aminotransferase, and alkaline phosphatase (ALP) were significantly elevated in either group, as were the activities of certain hepatic antioxidant enzymes (superoxide dismutase, glutathione-S-transferase) in the DCF 2000 group. The transcriptomic profile of selected genes in the tissues of exposed fish was affected as well. Significant changes in plasma total proteins, ammonia, ALT, and ALP, as well as in the transcription of genes related to thyroid function and the antioxidant defense of the organism, were found even in fish exposed to the lower DCF concentration (DCF 20). As it was chosen to match DCF concentrations commonly detected in aquatic invertebrates (i.e., the potential feed source of fish), it can be considered “environmentally relevant”. Future research is necessary to shed more light on the dietary NSAID toxicity to fish.

Silver and Copper Complexes with Ibuprofen and Caffeine-Preparation and Evaluation of Their Selected Biological Effects.

Several organometallic complexes based on more than twenty different metals have already been approved for medical applications. The aim of the presented research was to obtain complexes of silver and copper with the non-steroidal anti-inflammatory drugs ibuprofen and xanthine alkaloid caffeine and evaluate selected aspects of their bioactivity and biosafety in terms of their future possible applications. The obtained complexes were characterized by Fourier-transform infrared spectroscopy, thermogravimetry, UV-VIS spectroscopy, conductometry, elemental analysis, and bioassays. Cytotoxicity for normal human cells of the CCD-Co18 cell line was evaluated by determining the IC50 value, with metabolic and morphology assessments. It was observed that complexes containing ibuprofen and caffeine exhibited lower toxicity than those with ibuprofen only. Complexes with copper showed lower toxicity towards healthy human fibroblasts compared to silver-based compounds, with an IC50 above 140 μg mL-1. However, in the silver complexes, the presence of caffeine increased the potency of COX-2 inhibition. Antimicrobial effects against different Gram-positive and Gram-negative bacterial strains were evaluated by MIC determination with values less than 20 μg mL-1.

Intergenerational effects on fertility in male and female mice after chronic exposure to environmental doses of NSAIDs and 17α-ethinylestradiol mixtures

Non-steroidal anti-inflammatory drugs (NSAIDs) and 17α-ethinylestradiol (EE2) are extensively used in human and veterinary medicine. Due to their partial removal by wastewater treatment plants, they are frequent environmental contaminants, particularly in drinking water. Here, we investigated the adverse outcomes of chronic exposure to mixtures of NSAIDs (ibuprofen, 2hydroxy-ibuprofen, diclofenac) and EE2 at two environmentally relevant doses in drinking water, on the reproductive organ development and fertility in F1-exposed male and female mice and in their F2 offspring. In male and female F1 mice, which were exposed to these mixtures, reproductive organ maturation, estrous cyclicity, and spermiogenesis were altered. These defects were observed also in F2 animals, in addition to some specific sperm parameter alterations in F2 males. Transcriptomic analysis revealed significant changes in gene expression patterns and associated pathways implicated in testis and ovarian physiology. Chronic exposure of mice to NSAID and EE2 mixtures at environmental doses intergenerationally affected male and female fertility (i.e. total number of pups and time between litters). Our study provides new insights into the adverse effects of these pharmaceuticals on the reproductive health and will facilitate the implementation of a future regulatory environmental risk assessment of NSAIDs and EE2 for human health.

Localization of the ibuprofen molecule in model lipid membranes revealed by spin-label-enhanced NMR relaxation

Non-steroidal anti-inflammatory drugs (NSAIDs) have antipyretic, anti-inflammatory and analgesic effects, and can be used in the treatment of various diseases. These drugs have also a number of side effects, which may be related to their interaction with lipid membranes. In this study, we use the spin-labeled NSAID ibuprofen (ibuprofen-SL) as a relaxation enhancer to study its interaction with model lipid membranes employing liquid-state 1H NMR at 500 MHz. The high magnetic moment of unpaired electron in the spin label made it possible to reduce the concentration of the studied drug in the membrane to tenths of a mole percent. As model membranes, unilamellar POPC liposomes and bicelles consisting of a 2:1 mixture of DHPC:DMPC or DHPC:POPC lipids were used. An increase in the rate of proton spin-lattice relaxation, T1−1, selectively detected for protons at different positions in the lipid molecule, showed that ibuprofen-SL is localized in the hydrophobic part of the lipid bilayer. As the concentration of ibuprofen-SL increases to 0.5 mol%, the distribution of positions of ibuprofen-SL across the bilayer becomes wider. In the presence of 20 mol% of cholesterol, ibuprofen-SL is displaced from the core of the membrane to a region closer to the head group of the bilayer. This displacement was also confirmed by the NMR NOESY experiment conducted with unlabeled ibuprofen. For bilayers containing unsaturated POPC lipids, the distribution of ibuprofen positions across the bilayer becomes narrower compared to the presence of saturated DMPC lipids.

Low cross-linked terpenes-based porous polymers with reduced content of divinylbenzene: synthesis, physicochemical properties and sorption abilities

The low cross-linked porous polymers were prepared using terpene compounds (citral, limonene and pinene) and divinylbenzene with a suspension method. The prepared materials were characterized by: ATR-FTIR, low temperature nitrogen adsorption–desorption, TGA, swelling ratio and solid phase extraction (SPE) experiments. ATR-FTIR verified the chemical structures of the polymers. All the materials had developed internal structure with SBET in the range of 45–190 m2/g and high thermal stability. Sorption properties of the terpene-based polymers were tested for phenolic compounds (phenol, 2-chlorophenol, 2,4-dichlorophenol and 2,4,6-trichlorophenol) and popular non-steroidal anti-inflammatory drugs (aspirin, paracetamol and ibuprofen) and an antibiotic (ampicillin) with a dynamic solid phase extraction (SPE) method. The recoveries of 2,4-dichlorophenol and 2,4,6-trichlorophenol remained at a level 80–100% for all new materials even for 10–13 concentration cycles. Very high recoveries (70–100%) were also obtained for ibuprofen and aspirin from the citral- and limonene-based polymers using one-component solutions. However, when using ternary component solutions, the maximum recoveries of ibuprofen reached 70%. Paracetamol recoveries did not exceed 20%, while these for ampicillin ranged from 40 to 80%. The performed studies have proven that the process is affected by both chemical nature of adsorbents and adsorbates. Especially in the case of multicomponent solutions, the acid—base balance of solutes in the solution and on the polymer—solution interface should be taken into account as an important factor determining obtained recoveries.

Heterologous Platelet-Rich Plasma in the Treatment of Severe Skin Damage

Accidental soft tissue injuries are a frequent injury. Platelet-rich plasma (PRP) is an interesting therapeutic option for wounds and skin damage. In this case report, we describe a 37-year-old man that presented to our ward of pain medicine for an accidental severe leg injury associated with skin and soft tissue loss, with severe pain and poor sensation. History revealed the use of recreational drugs without viral infections or systemic diseases. Wound debridement, wound dressings, systemic antibiotics (amoxicillin 1000 mg tid and azithromycin 500 mg od), and non-steroidal anti-inflammatory drugs (ibuprofen 600 mg bid) reduced pain but did not improve the skin and soft tissue. A fibrin membrane with concentrated growth factors was applied, yielding an improvement in the injury in 16 months without the need for skin grafting.

Synthesis of curcumin derivatives containing non-steroidal anti-inflammatory drugs

Synthesis and biological evaluation of hybrid molecules combining naturally occurring antioxidant active structures with anti-inflammatory agents has been a strong trend in medicinal chemistry. This study focuses on modulating the structure of curcumin derivatives or their analogues with the use of non-steroidal anti-inflammatory drugs (NSAIDs). The combinations of curcumin, its keto-blocked derivatives and monocarbonyl analogues with selected non-steroidal anti-inflammatory drugs (ibuprofen, naproxen) were obtained and characterized. The pyrazole, isoxazole, benzylidene derivatives as well as curcumin monocarbonyl analogues were used as substrates in the reactions with selected NSAIDs. As a result of the esterification of curcumin-type diphenol, the corresponding mono- and diester-type derivatives were also obtained and characterized. Moreover, the estimated values of binding affinities and the binding sites of docked derivatives were deduced from modeling studies were very favorable. Results obtained show the binding potential of curcumin and its analogs to the host-targeted proteins nucleocapsid phosphoprotein (PDB ID: 6VYO) structure. Additionally, with the use of selected methods of computational chemistry (Molinspiration Cheminformatics and Osiris Property Explorer) the molecular parameters of the relevant molecules were calculated.

Cardiovascular risks of continuing vs. initiating NSAIDs after first-time myocardial infarction or heart failure: a nationwide cohort study.

It is unknown whether the cardiovascular risks associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) shortly after first-time myocardial infarction (MI) or heart failure (HF) differ between patients continuing and initiating use. Using nationwide health registries, we conducted a cohort study of all patients with first-time MI or HF during 1996-2018 (n=273 682). NSAID users (n=97 966) were categorized as continuing (17%) and initiating (83%) users according to prescription fillings<60 days before index diagnosis. The primary outcome was a composite of new MI, HF admission, and all-cause death. Follow-up started 30 days after the index discharge date. We used Cox regression to compute hazard ratios (HRs) with 95% confidence intervals (CIs) comparing NSAID users vs. non-users. The most commonly filled NSAIDs were ibuprofen (50%), diclofenac (20%), etodolac (8.5%), and naproxen (4.3%). The composite outcome HR of 1.25 (CI: 1.23-1.27) was driven by initiators (HR=1.39, 1.36-1.41) and not continuing users (HR=1.03, 1.00-1.07). The lack of association among continuing users was also observed for individual NSAIDs (ibuprofen and naproxen), except diclofenac (HR=1.11, 95% CI: 1.05-1.18). Among initiators, the HR was 1.63 (CI: 1.57-1.69) for diclofenac, 1.31 (CI: 1.27-1.35) for ibuprofen, and 1.19 (CI: 1.08-1.31) for naproxen. The results were consistent for both MI and HF patients, the individual components of the composite outcome, and various sensitivity analyses. NSAID initiators were more susceptible to adverse cardiovascular outcomes after first-time MI or HF than continuing users.

Impact of hemoglobin A1c level on the association between non-steroidal anti-inflammatory drug use and cardiovascular events in patients with type 2 diabetes: A population-based cohort study.

Non-steroidal anti-inflammatory drugs (NSAIDs) should be used cautiously in patients with type 2 diabetes. We examined whether the cardiovascular risks associated with NSAID use depended on HbA1c level in patients with type 2 diabetes. We conducted a population-based cohort study of all adult Danes with a first-time HbA1c measurement ≥48 mmol/mol during 2012-2020 (n = 103 308). We used information on sex, age, comorbidity burden, and drug use to calculate time-varying inverse probability of treatment weights. After applying these weights in a pooled logistic regression, we estimated hazard ratios (HRs) of the association between use of NSAIDs (ibuprofen, naproxen, or diclofenac) and cardiovascular events (a composite of myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation or flutter, and all-cause death). We stratified all analyses by HbA1c level (<53 or ≥53 mmol/mol). For ibuprofen use, the HR of a cardiovascular event was 1.53 (95% confidence interval [CI]: 1.34-1.75) in patients with HbA1c <53 and 1.24 (95% CI: 1.00-1.53) in patients with HbA1c ≥53 mmol/mol. For naproxen use, the HR was 1.14 (95% CI: 0.59-2.21) in patients with HbA1c <53 and 1.30 (95% CI: 0.49-3.49) in patients with HbA1c ≥53 mmol/mol. For diclofenac use, the HR was 2.40 (95% CI: 1.62-3.56) in patients with HbA1c <53 and 2.89 (95% CI: 1.65-5.04) in patients with HbA1c ≥53 mmol/mol. In patients with type 2 diabetes, glycemic dysregulation did not affect the cardiovascular risk associated with NSAID use.

Development of an electrochemical cyclooxygenase biosensor to evaluate target–drug viability and interactions

In this research, we developed a biosensor to analyze the anti-inflammatory properties of non-steroidal anti-inflammatory drugs (NSAIDs) and potential candidate molecules. The chemical interaction between commercial NSAIDs and their target, the cyclooxygenase-2 enzyme (COX), was studied using electrochemical techniques and electronic paramagnetic resonance (EPR). The modified electrode, COX@GCE biosensor, presented two main reduction processes. We observed that the first one involves one electron and one proton related to tyrosyl radical reduction to tyrosine, and the second comprises a one-electron reduction from the Fe (IV) to Fe (III) species present in the enzyme’s active site, which in the presence of hydrogen peroxide results in a catalytical process. Based on these results, an electrochemical mechanism of the COX enzyme is proposed. Additionally, the quantitative inhibitory interaction mechanisms of six commercial NSAIDs were studied using this biosensor. The NSAIDs acetylsalicylic acid, dipyrone, and ibuprofen presented the higher COX inhibitory percentual, being, therefore, the most effective NSAIDs among the studied group. Salicylic acid also presented a significant inhibition capability in both electrochemical and EPR studies. The effect of some NSAIDs, e.g., dipyrone and acetaminophen, can be explained by the redox inhibition hypothesis and can be related to the direct interaction and inactivation of the iron present in the enzyme’s active site. Ibuprofen and naproxen presented irreversible COX inhibition. Despite that, the EPR shows that these drugs have relatively weak interactions with the COX active site, suggesting they should interact with the external structures resulting in the inhibition of its activity. Finally, the developed enzymatic sensor presented a high potential to study the anti-inflammatory properties of well-known drugs and can be a useful tool in the development of new NSAIDs, in a more efficient way, therefore presenting high applicability in drug development, pharmaceutical, and biomedical applications in both academia and industry.

In vitro anti-proliferative, and in silico ribonucleotide reductase and pharmacokinetics studies of heteroleptic silver(I), nickel(II) and copper(II) complexes of 4-methyl-3-thiosemicarbazones and ibuprofen

ObjectivesThe present research focuses on the in vitro anti-proliferative, and in silico ribonucleotide reductase and pharmacokinetics studies of twelve heteroleptic metal complexes of the general formulae [Ag(L1−4)(ibu)] (1–4) and [M(L1−4)(ibu)2] (5–12), where L1−4 = 2-(1-(4-substitutedphenyl)ethylidene)-N-methylhydrazinecarbothioamide, ibu = non-steroidal anti-inflammatory drug (ibuprofen), and M = Cu(II) and Ni(II). MethodsVarious spectroscopic techniques were used to authenticate the structure of the synthesized complexes. UV-Vis and cyclic voltammetry techniques were used to analyse the stability and the reducing ability of the complexes. In vitro anti-proliferative studies by MTT assay, apoptotic behaviour and cellular uptake studies were investigated followed by the in silico interaction with ribonucleotide reductase (RNR) enzyme. ResultsThe spectral studies predicted distorted tetrahedral geometry around silver(I) ion and distorted octahedral geometry around nickel(II) and copper(II) ions. The reducing ability of the copper(II) complexes was analysed using ascorbic acid by UV-Vis and cyclic voltammetry techniques, which authenticate the reducing ability of the complexes and the possible interactions within the cells. The in vitro anti-proliferative activity of the synthesized complexes against three cancerous (estrogen positive (MCF-7), estrogen negative (MDA-MB-231) and pancreatic (PANC-1)) and one normal (MCF-10a) cell lines by MTT assay showed enhanced activity for copper(II) complexes 11 and 12 containing the hydrophobic substituents. The apoptotic and cellular uptake studies showed that the complex 12 is readily taken up by PANC-1 cell lines and induces ROS-mediated mitochondrial and caspase-dependent apoptosis. The in silico studies indicated hydrogen bonding, hydrophobic and π-pair (π–π, π–σ and π–cation) interactions between the complexes and the ribonucleotide reductase (RNR) enzyme. The in silico pharmacokinetics studies of the complexes predicted the drug-likeness characteristics of the complexes. ConclusionThe synthesized complexes are found to be less toxic to normal cells and inhibit the growth of cancerous cells by inducing mitochondrial-mediated and caspase dependent apoptotic pathway in PANC-1 cells.

Spatial variations and ecological risks assessment of pharmaceuticals and personal care products (PPCPs) in typical lakes of Wuhan, China

Lakes are terminal sink of PPCPs, since PPCPs were transported to aquatic system from wastewater treatment plant effluent. Meanwhile, the ecological risks caused by PPCPs to the lakes have aroused wide concern. This study investigated the presence and distribution of PPCPs in 19 typical lakes in Wuhan city; the short term and long-term ecological risk were assessed. The concentration of ten typical PPCPs and the correlation between PPCPs and water quality parameters were analyzed. Ten PPCPs were widely detected, showing that these PPCPs were abundant in the research region. The total PPCPs concentrations varied from 0.44 to 2.1 * 102 ng/L in water sample and ≤ 5.3 ng/g in sediments. According to the results, two nonsteroidal anti-inflammatory drugs (ibuprofen, naproxen) were predominated compared to other PPCPs tested in the lakes of Wuhan city. The Pearson correlation analysis revealed a substantial positive correlation (p < 0.01) between NH4+-N and ibuprofen concentration, indicating that ibuprofen could be produced from the same sources of NH4+-N. Some PPCPs has shown positive correlation (p < 0.01) with suspended particles in concentrations. A negative correlation in water-sediment distribution for PPCPs was also observed. The potential ecological risks of PPCPs to the lakes were further evaluated. Results implied that ofloxacin posed the highest potential short-term risk of all the ten PPCPs. Sulfadiazine, sulfamethoxazole and roxithromycin posed a potential long-term risk in Niushan lake. This study investigated PPCPs distribution on a large spatial scale in Wuhan lakes in the post-epidemic era and revealed the importance of ofloxacin control in Wuhan. The findings of this work suggests that the long-term management for lake ecosystems is crucial.

Neonicotinoids and pharmaceuticals in hair of the Red fox (Vulpes vulpes) from the Cavallino-Treporti peninsula, Italy

Neonicotinoids (NEOs) and active pharmaceuticals ingredients (API) are contaminants widely diffused worldwide, causing increasing concern for potential adverse effects on wildlife. However, research on these contaminants have focused on target and non-target invertebrates, while information on potential effects in terrestrial mammals is lacking. We performed preliminary non-invasive monitoring of NEOs and API in a suburban and agricultural area using hair of the Red fox. The Red fox is a widely diffused mesopredator in Europe, and its plasticity in feeding habits makes it an excellent indicator for assessing exposure to environmental contamination. We observed the presence of NEOs in many Red fox hair samples (n = 11), including imidacloprid (IMI), acetamiprid (ACE), and clothianidin (CLO). The highest quantified concentrations were 6.4 ng g−1 dry weight (dw), 6.7 ng g−1 dw, and 0.9 ng g−1 dw for IMI, ACE, and CLO, respectively. The targeted APIs included non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants. APIs were less frequently detected than NEOs, and the compounds with the highest prevalence were the NSAID ketoprofen (36%), the antidepressant sertraline (36%), and its active metabolite norsertraline (27%). The presence of human pharmaceuticals such as the NSAID ibuprofen and the antidepressants sertraline, fluoxetine, and their active metabolites norsertraline and norfluoxetine suggest environmental contamination due to untreated and partially treated wastewater discharged in surface waters and soils of the study area. The detection and quantification of ketoprofen and flunixin also suggest the possible use of contaminated manure on farmland. Findings indicate that hair may be used for monitoring environmental exposure to NEOs and provide evidence that hair is a good marker of exposure for antidepressants and certain NSAIDs, including ibuprofen, ketoprofen, and flunixin.

Epipericardial fat necrosis: a case report of an underdiagnosed disease.

Epipericardial fat necrosis: a case report of an underdiagnosed disease.

Response of hepatic biochemical parameters and neurotoxicity to carbamazepine and ibuprofen in Oreochromis mossambicus.

Globally, the prevalence and pollution of pharmaceutical drugs in aquatic environments have been steadily increasing. This study sought to evaluate the effects of 14days of exposure to environmental-relevant doses (ibuprofen 0.5, 5, and 50µg/L, and carbamazepine 0.005, 1, and 10µg/L) of the nonsteroidal anti-inflammatory drugs ibuprofen and carbamazepine in the freshwater fish Oreochromis mossambicus. The results showed a significant (P < 0.05) decrease in O. mossambicus superoxide dismutase, catalase, biotransformation enzymes, glutathione-s-transferase, glutathione peroxidase, oxidative stress lipid peroxidation, protein carbonyl activity, cellular damage metallothionine, reduced glutathione, immunological activities, and respiratory burst activity. Consequently, the acquired data revealed that O. mossambicus treated with ibuprofen and carbamazepine shows more significant alterations in metabolic depression, biochemical parameters, and oxidative stress. In addition, increased neurotoxic effects were observed in ibuprofen and carbamazepine treated O. mossambicus.