Potential Toxicity Risk Research Articles

Composition, Bioactivities, Microbiome, Safety Concerns, and Impact of Essential Oils on the Health Status of Domestic Animals

Essential oils (EOs) are highly concentrated and volatile blends of nonpolar substances that are derived from aromatic plant components and comprise terpenes, terpenoids, and phenylpropanoids, exhibiting diverse biological and pharmacological properties. The burgeoning pet industry is interested in EOs as a potential solution for common health issues in domestic animals, particularly in addressing antimicrobial resistance. The present literature review summarizes the composition, properties, benefits, safety considerations, and effects of EOs on domestic animals. The applications of EOs range from antimicrobial effects to antioxidant, anti-inflammatory, and anticancer activities, etc. The chemical constituents of EOs, exemplified by eucalyptus EO and rosemary EO, highlight their distinct aromatic profiles and potential benefits. Nevertheless, understanding the chemical makeup of EOs is fundamental to assessing their potential impacts on biological systems. The gut microbiota plays a crucial role in regulating various metabolic processes in the host, including energy homeostasis, glucose metabolism, and lipid metabolism. Safety considerations, including potential toxicity risk awareness, are essential when incorporating EOs into animal care routines. The feed additives incorporating EOs have shown promise in influencing gut microbiota balance, reducing inflammation, and acting as antioxidants. However, considering the potential risks associated with high doses or multiple administrations, cautious application is paramount. Preliminary studies suggest low toxicity levels, but further research is required to evaluate the safety of EOs. Though studies have reported the beneficial effects of EOs on pets and animals, further research is needed to validate the findings in real-world conditions. The paper also discussed the regulatory considerations and future perspectives on applying EOs in veterinary medicine.

Advancing Ocular Medication Delivery with Nano-Engineered Solutions: A Comprehensive Review of Innovations, Obstacles, and Clinical Impact.

Recent advancements in ocular drug delivery have led to the introduction of a range of nanotechnology-based systems, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, inorganic nanoparticles, niosomes, liposomes, nanosuspensions, dendrimers, nanoemulsions, and microemulsions. These systems enhance drug retention, penetration, bioavailability, and targeted delivery, promising prolonged drug release, and improved patient compliance. However, their interactions with biological systems pose potential toxicity risks, necessitating a careful evaluation of nanoparticle size, shape, surface charge, and coating. Traditional ocular drug delivery methods, like topical applications and injections, face challenges due to anatomical and physiological barriers, leading to frequent dosing and systemic toxicity risks. Nanocarriers offer solutions by improving drug permeation and targeted delivery, yet translating these innovations from research to clinical practice involves overcoming hurdles related to manufacturing scale-up, quality control, regulatory approval, and cost-effectiveness. The quality by design (QbD) framework provides a systematic approach to optimize nanocarrier formulation and process design, ensuring safety and efficacy. Assessing the safety of nanocarriers through in vivo and in vitro studies is crucial for their clinical application. This review explores the use of various nanomedicines in ocular drug delivery, highlighting the current state of ocular medication delivery and considering critical aspects such as scaling up and clinical applications.

Effect of Nitrates supplementation on Muscle Hypertrophy and Athletic Performance: A Narrative Review

Background and Study Aim. The consumption of nitrate has been linked to various advantages, including aiding recovery by lessening fatigue, enhancing oxygen supply to muscles, and increasing the elimination of metabolic by-products during intense physical activity. Given the rising trend of utilizing dietary supplements for peak athletic performance, this literature review aims to explore the role and promise of nitrate supplementation in influencing muscle function and boosting physical prowess, while also shedding light on its potential perks and drawbacks. Material and Methods. Electronic databases including Web of Science (all databases), PubMed, Scopus, Google Scholar, Science Direct, were explored on June 11, 2022. The search terms were drawn from prior systematic reviews on nitrate supplementation and exercise and informed by a recent narrative review on Nitrates impact on athletic performance and muscle hypertrophy. Results. The findings of this review indicate that nitrate intake, owing to its ability to widen blood vessels, could potentially enhance blood flow and oxygen delivery to muscles during exercise. Consequently, this improved circulation might facilitate better nutrient and oxygen transportation to muscle tissue, thereby fostering muscle development through enhanced nutrient absorption and waste removal during physical exertion. However, it's crucial to note that excessive nitrate consumption might trigger adverse effects related to the formation of nitrosamines. Conclusion. In summary, investigations into the potential advantages of nitrate supplementation, whether through dietary sources or supplements, in augmenting athletic performance are promising. This is evident from the observed effects of increased muscle protein synthesis, reduced muscle soreness, and enhanced cognitive function under stressful conditions. Nonetheless, it's imperative to exercise caution against over-supplementation due to the potential risks of toxicity and associated side effects.

Narrative literature review: Effect of Branched-chain Amino Acids (BCAAs) on muscle hypertrophy and athletic performance

Background and Study Aim. Branched-chain amino acids (BCAAs) have received considerable attention in sports science due to their potential benefits in improving athletic performance and promoting muscle recovery. BCAAs including leucine, isoleucine, and valine, are essential amino acids that are important for muscle protein physiology. To date, studies have shown positive effects of BCAA supplementation on muscle recovery, muscle soreness, and cognitive function. Hence, with the growing popularity of using dietary supplements for optimal athletic performance, this narrative literature review aims to investigate the role and potential of BCAA supplementation to influence muscle function and improve physical performance, while highlighting the potential benefits and side effects associated with their supplementation. Material and Methods. The current review was conducted according to PRISMA (Preferred reporting items for systematic review and meta-analysis) guidelines. Electronic databases including Web of Science (all databases), PubMed, Scopus, Google Scholar, Science Direct, were explored on June 11, 2022. Results. Based on recent evidence, BCAAs have been shown to reduce muscle damage, improve muscle recovery and repair, increase muscle protein synthesis, and maintain muscle mass during periods of energy restriction, however may also have some potential side effects such as liver damage, kidney dysfunction and negative effects on glucose metabolism. Conclusion. In conclusion, studies investigating the potential benefits of BCAAs obtained from supplementation and diet to improve athletic performance are promising due to their demonstrated effects in increasing muscle protein synthesis, reducing muscle soreness, and improving cognitive function under stress. Nevertheless, excessive supplementation should be avoided due to the potential risk of toxicity and side effects.

IN SILICO TRIAL APPROACHES BETWEEN PHYTOCHEMICAL COMPOSITION OF VERBENA OFFICINALIS AND LIVER CANCER TARGETS

Objective: The abundance of bioactive metabolites in Verbena officinalis explains the biological benefits and folkloric use of the plant. Liver cancer is an extremely heterogeneous malignant disease compared to other defined tumors. To explore the potential therapeutic value of bioactive metabolites in Verbena officinalis, this study aimed to filter secondary metabolites, conduct ADME-Tox assessments, perform drug similarity tests, and analyze with molecular dynamic simulations. The objective was to evaluate how potential drug candidates derived from Verbena officinalis behave in biological systems and assess their potential toxicity risks. Material and Method: Ligands selected from the ADME assay were utilized in in silico molecular docking studies against Glucose-6-phosphate dehydrogenase enzyme in the oxidative part of the pentose phosphate pathway, which is crucial for liver diseases. These studies were conducted using Autodock Vina embedded in Chimera 1.16. Molecular dynamics simulations were performed with the AMBER16. Result and Discussion: When the ADME test results were evaluated, 88 secondary metabolites were identified as ligands. Among all the ligands evaluated against Glucose-6-phosphate dehydrogenase enzyme, which is the key enzyme of the pentose phosphate pathway, quercetin flavonoid was determined to be the most active ligand with a docking score of -8.1 kcal/mol and binding energy of -118.51 kcal/mol. A molecular dynamics simulation performed for 300 nanoseconds confirmed that quercetin can remain stable in its microenvironment. The activity of this metabolite is worthy of further testing in vitro and in vivo as it may highlight a therapeutic modality within the pentose phosphate pathway.

Machine learning exploring the chemical compositions characteristics and sources of PM2.5 from reduced on-road activity

Particulate nitrate pollution has emerged as a major contributor to haze events in urban environment, due to the rapid increase of vehicle emissions. However, a comprehensive formation mechanisms of PM2.5 responses to vehicle emissions control still remains high uncertainties. In our study, hourly criteria air pollutants, meteorological parameters and chemical compositions of PM2.5 were continuously measured with or without reduced on-road activity at the coastal city in southeast China. XG Boost-SHAP models analysis showed that increasing concentrations of NO3−, NH4+, and BC contribute to elevated PM2.5 levels, due to the influence of vehicle emissions. Based on PMF model results, there was a notable increase in the contributions of traffic-related emissions, industrial activities, and dust sources to PM2.5, with increments of 13%, 4%, and 7%, respectively. In addition, metal elements such as Mn emerged as the primary contributor to hazard quotient (HQ) values, originated from non-exhaust emissions of vehicles, which might cause the potential toxic risks on human health, particularly during haze events. Hence, this study improve the understanding of air quality and human health both direct and indirect responses to vehicle emissions control in future urban management.

The Role of Oxidative Stress and DNA Hydroxymethylation in the Pathogenesis of Benzo[a]pyrene-Impaired Reproductive Function in Male Mice.

Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon, is known to cause teratogenesis. Environmental exposure of BaP has led to wide public concerns due to their potential risk of reproductive toxicity. However, the exact mechanism is still not clear. We aimed to explore the alterations of oxidative stress and DNA hydroxymethylation during BaP-impaired reproductive function. BALB/c mice were intragastrically administered with different doses of BaP (0.01, 0.1, and 1 mg/kg/day, once a day), while control mice were administered with corn coil. Then, the reproductive function, alterations of oxidative stress, DNA methylation, and DNA hydroxymethylation of testis tissues were evaluated. We found that BaP caused obvious histopathological damages of testis tissues. As for sperm parameters after BaP administration, testis weight and the rate of teratosperm were increased, as well as sperm count and motility were decreased. In mechanism, BaP upregulated HO-1 and MDA levels and downregulated SOD and CAT activity and GSH content in testis tissues, indicating that oxidative stress was induced by BaP. Furthermore, a significant induction of hydroxymethylation and inhibition of methylation were observed in testis tissues after BaP exposure. Collectively, BaP-induced oxidative stress and hydroxymethylation were involved in impairing reproductive function, which may be the mechanism of the male infertility.

Perchlorate in foodstuffs from South China and its implication for human dietary exposure

Perchlorate, an aqueous-soluble compound resistant to degradation, is mainly used in the synthesis of pyrotechnics, herbicides, and other products. It serves as a pivotal component in the production of fireworks, rocket fuel, and explosives. Perchlorate was recognized as a pollutant owing to the potential toxic risk to thyroid function, which could pose a potential threat to the nervous system of infants and pregnant women. Some study had found that perchlorate existed in food, water and air. This study aimed to investigate the levels of perchlorate in six types of foods (n = 570) from South China, and evaluate potential exposure risks for residents. Vegetables were found to have the highest median levels of foods, attributed to elevated water content in leafy vegetables and facile solubility of perchlorate in water. The relatively low levels of perchlorate in food compared to other studies could attribute to the fact that the period of food we purchased in this study was during the wet season while the contaminants, such as perchlorate, were diluted. The maximum hazard quotient (HQ) values for all residents consuming different foods and water were all higher than 1 This suggested that there is a potential health risk of perchlorate to residents in South China. Those may be attributed to the high levels of perchlorate in some individual samples of meat and eggs. However, the 95th percentile of HQ values in all residents was less than 1, indicating that there is no potential health risk of perchlorate to most residents in South China.

Application of molecularly imprinted polymers in the water environmental field: A review on the detection and efficient removal of emerging contaminants

The emerging contaminants in the environment pose a threat to ecological security and human health. At present, traditional technologies are difficult to detect and remove existing trace emerging contaminants in water bodies. Therefore, efficient removal of low concentration emerging contaminants is a key issue in ensuring water safety. As an emerging technology, molecular imprinting technology (MIT) can synthesize polymers with specific recognition ability for target pollutants, providing a new approach for efficient removal of emerging contaminants. It is worth noting that combining MIT with traditional catalysts is an effective method to improve detection limits and removal efficiency. This review mainly introduced the research progress of using MIT to detect pollutants in various sensors and using advanced oxidation technology to remove pollutants in recent years, focusing on the preparation and application of MIT-based photocatalysts, electrocatalysts, and Fenton-like catalysts. In addition, possible interactions between the target analyte and MIT were discussed, as well as the reusability and stability of imprinted catalysts in water treatment, and their potential ecological toxicity risks were analyzed. Finally, the challenges of MIT based pollutant mitigation and the application prospects of molecular imprinting technology in environmental analysis were elaborated from multiple perspectives.

Chlorinated Anthracenes Induced Pulmonary Immunotoxicity in 3D Coculture Spheroids Simulating the Lung Microenvironment.

Chlorinated anthracenes (Cl-Ants), persistent organic pollutants, are widely detected in the environment, posing potential lung toxicity risks due to frequent respiratory exposure. However, direct evidence and a comprehensive understanding of their toxicity mechanisms are lacking. Building on our prior findings of Cl-Ants' immunotoxic risks, this study developed a three-dimensional coculture spheroid model mimicking the lung's immune microenvironment. The objective is to explore the pulmonary immunotoxicity and comprehend its mechanisms, taking into account the heightened immune reactivity and frequent lung exposure of Cl-Ants. The results demonstrated that Cl-Ants exposure led to reduced spheroid size, increased macrophage migration outward, lowered cell viability, elevated 8-OHdG levels, disturbed anti-infection balance, and altered cytokine production. Specifically, the chlorine substituent number correlates with the extent of disruption of spheroid indicators caused by Cl-Ants, with stronger immunotoxic effects observed in dichlorinated Ant compared to those in monochlorinated Ant. Furthermore, we identified critical regulatory genes associated with cell viability (ALDOC and ALDOA), bacterial response (TLR5 and MAP2K6), and GM-CSF production (CEBPB). Overall, this study offers initial in vitro evidence of low-dose Cl-PAHs' pulmonary immunotoxicity, advancing the understanding of Cl-Ants' structure-related toxicity and improving external toxicity assessment methods for environmental pollutants, which holds significance for future monitoring and evaluation.

#246 Understanding the impact of antiangiogenic drug-induced proteinuria on kidney function in cancer patients

Abstract Background and Aims Proteinuria is a common adverse event associated with the use of vascular endothelial growth factor (VEGF) inhibitor drugs, which are widely employed in oncology for treating various tumors. The incidence of proteinuria of all degrees ranges from 10% to 90%, with proteinuria in the nephrotic range occurring in 1-5% of cases. VEGF plays a crucial role in maintaining the integrity of the glomerular capillary wall. Podocytes, constitutively express VEGF, and VEGF receptors are present on both the surface of glomerular capillary endothelial cells and podocytes. Any disruption in the podocyte-endothelial VEGF axis can lead to the loss of endothelial fenestrations in glomerular capillaries, proliferation of glomerular endothelial cells, loss of podocytes, and subsequent proteinuria. The most common pathological findings include focal segmental glomerulosclerosis and minimal change nephropathy, typically associated with tyrosine kinase inhibitors (TKIs), as well as thrombotic microangiopathy (TMA), more frequently observed in pts treated with anti VEGF. Proteinuria is a recognized risk factor for progressive renal damage and end-stage renal disease. However, it's worth noting that the average treatment duration for patients on anti-angiogenic therapy is considerably shorter than the time indicated by clinical studies as necessary to induce renal damage from proteinuria in healthy individuals. However, the long-term impact of drug-induced proteinuria on renal function remains uncertain. The aim of the study is to investigate the association between proteinuria induced by anti-VEGF/VEGFR drugs and its long-term effects on renal function in cancer patients. Method A retrospective study was conducted on 124 patients undergoing anti-VEGF/VEGFR therapy for ≥6 months. 45% of the patients enrolled in the study were on TKI monotherapy, 36% received TKI plus immune checkpoint inhibitors (ICIs), 10% received anti- VEGF treatment, 7% received TKI + chemotherapy (CT), and 2% received anti-VEGF + ICIs. Among patients, 51% were undergoing treatment for kidney cancer, 25% for thyroid cancer, 14% for colon cancer, 7% for liver cancer, and 5% for lung cancer. The study assessed the time course of estimated glomerular filtration rate (eGFR), the influence of baseline eGFR on subsequent variations, the association between proteinuria and renal function, and the identification of risk factors for proteinuria or renal failure. Proteinuria was quantified as proteinuria/24 h. Results Among the 124 patients, 53 developed proteinuria <1 g/24 h, 41 between 1-3 g/24 h, and 30 >3 g/24 h. Specific data are outlined in Table 1. A trend toward a reduction in eGFR of −5 ml/min/1.73 m2 was observed in all patients after 2 years of treatment. The high proteinuria group exhibited a greater percentage change in eGFR compared to the other groups (−1.5% vs −8.5% vs −12.3%) as depicted in Fig. 1A, along with a time-dependent decrease in eGFR. There was no significant difference in the development of eGFR <30 ml/min/1.73 m2 between groups, and no patients permanently discontinued treatment due to nephrotoxicity. No differences in eGFR reduction were noted among the three groups categorized by baseline eGFR (Fig. 1B). Importantly, renal function after the end of therapy was found to be reversible. Conclusion The study did not find a correlation between the degree of proteinuria secondary to anti-VEGF/VEGFR and significant reductions in renal function. Therefore, treatment can be continued irrespective of the degree of proteinuria. Clinical decisions regarding the continuation of therapy with these drugs should weigh the benefits in terms of survival against the potential risks of toxicity, including a modest reduction in renal glomerular filtration rate.

Nutritional insights into broths in relation to elemental composition

Despite the popular claim that broths are a good source of essential elements, few studies have been devoted to clarifying this narrative. In fact, there is growing concern about the risk of ingesting toxic elements. This study focused on assessing the content of important elements (Ca, Cd, Cu, Fe, K, Mg, Na, and Pb) in various types of broths (beef, fish, poultry, pork, and vegetable). The samples (n = 30) included broths of different origins, including laboratory-prepared broths and broths prepared by professional cooks from Czech school canteens. The broths were evaluated as potential sources of essential elements in relation to their reference daily intake, as well as their potential toxicity risk in relation to Cd and Pb. Although significant variability was observed in the contents of the investigated elements, the results generally contradicted the popular narrative that broths are a good source of Ca, Cu, Fe, and Mg, as their contents did not achieve even 5% of the recommended daily intake. The amount of Ca in the broths was minimal even compared to the amount in tap water. The consumption of broths poses minimal risk regarding the presence of Cd and Pb.Graphic abstract

Fast tumor imaging using pH-responsive aggregation of cyanine dyes with rapid clearance

Rapid and selective tumor detection using conventional pH-activatable chemical probes as contrast agents is challenging. Moreover, a large proportion of the contrast agent is usually retained in the body long-term, which causes potential toxicity risks. In this study, we developed a fluorescent sensor, CypH2S, with a pH-sensitive cyclic substructure for detection of acidic tumor microenvironment. Upon pH variation, the sensor underwent structural changes: the closed-ring form, CypH2S-C, exhibited suppressed dye aggregation, while the open-ring form, CypH2S-O, tended to aggregate in aqueous solutions under slightly acidic conditions. Importantly, CypH2S facilitated rapid and selective tumor visualization in a living mouse model via fluorescence imaging of its pH-responsive aggregation with a 1.9-fold tumor/background ratio (< 1 h). Furthermore, prompt clearance of CypH2S from the bloodstream post-tumor detection occurred because of the relatively small size of the aggregates and cell impermeability. These properties would make CypH2S a promising candidate for clinical tumor diagnosis.

Assessment of the impact of chemical pollution on endangered migratory fish in two major rivers of France, including spawning grounds

Water pollution is a one of the most contributors to aquatic biodiversity decline. Consequently, ecological risk assessment methods have been developed to investigate the effects of existing stresses on the environment, including the toxic effects of chemicals. One of the existing approaches to quantify toxic risks is called “Potentially Affected Fraction of species” (PAF), which estimates the potential loss of species within a group of species studied. In this study, the PAF method was applied to the Garonne catchment (southwest France) due to the limited information available on the involvement of water pollution in the decline of diadromous fish populations. This approach was used to quantify the potential toxic risk associated with chemical contamination of water for fish species. The objectives were to quantify this risk (1) in the Garonne and Dordogne rivers and (2) in the spawning grounds of two endangered anadromous fish species: the allis shad and the European sturgeon during the development period of their early life stages. Environmental pollution data was provided for 21 sites within the Garonne catchment between 2007 and 2022, and toxicity data was obtained specifically from freshwater toxicity tests on fish species. Then, for each site and each year, the potential toxic risk for a single substance (ssPAF) and for a mixture of substances (msPAF) was calculated and classified as high (>5 %), moderate (>1 % and < 5 %) or low (<1 %). Potential toxic risks were mostly moderate and mainly associated with: metals > other industrial pollutants and hygiene and care products > agrochemicals. In summary, this study highlights the probable involvement of water contamination on the decline, fate and restoration of diadromous fish populations in the Garonne catchment, focusing notably on the toxic effects on early life stages, a previously understudied topic.

Commercially available mouthguards: Unearthing trace elements for the first time

The use of mouthguards is advocated by the American Dental Association for orofacial injury prevention and teeth protection. However, the chemical environment in the mouth may cause harmful substances within the mouthguard's polymer material to leach out and be absorbed by the user. Considering this, the present study for the first time analyzed commercially available mouthguards and disclosed the presence of trace elements. Specifically, an analytical method was developed based on closed-vessel microwave-assisted digestion and plasma-based atomic spectrometry for determining toxic trace elements in mouthguard samples. Initially, 75 elements were assessed and, thereafter, quantified cadmium (Cd), copper (Cu) and lead (Pb) in each sample by inductively coupled plasma mass spectrometry (ICP-MS). Method validation was carried out by analyzing a certified reference material of Low-Density Polyethylene, and by addition and recovery experiments. Results for copper were further validated by ICP optical emission spectrometry (ICP-OES). While most samples exhibited elemental levels beneath the method's limit of quantification, Cd, Cu and Pb were detected in four samples. Remarkably, one sample had Cu levels exceeding safe limits by 109 times, highlighting potential toxicity risks. This initial research underscores the need for stricter contamination control in mouthguard materials to minimize potentially health hazards.

Differential inhibition of sildenafil and macitentan on saxagliptin metabolism

The development of diabetes mellitus (DM) is generally accompanied by erectile dysfunction (ED) and pulmonary arterial hypertension (PAH), which increases the use of combination drug therapy and the risk of drug-drug interactions. Saxagliptin for the treatment of DM, sildenafil for the treatment of ED and PAH, and macitentan for the treatment of PAH are all substrates of CYP3A4, which indicates their potential involvement in drug-drug interactions. Therefore, we investigated potential pharmacokinetic interactions between saxagliptin and sildenafil/macitentan. We investigated this speculation both in vitro and in vivo, and explored the underlying mechanism using in vitro hepatic metabolic models and molecular docking assays. The results showed that sildenafil substantially inhibited the metabolism of saxagliptin by occupying the catalytic site of CYP3A4 in a competitive manner, leading to the alterations in the pharmacokinetic properties of saxagliptin in terms of increased maximum plasma concentration (Cmax), area under the plasma concentration–time curve from time 0 to 24 h (AUC(0-t)), area under the plasma concentration–time curve from time 0 extrapolated to infinite time (AUC(0-∞)), decreased clearance rate (CLz/F), and prolonged terminal half-life (t1/2). In contrast, a slight inhibition was observed in saxagliptin metabolism when concomitantly used with macitentan, as no pharmacokinetic parameters were altered, except for CLz/F. Thus, dosage adjustment of saxagliptin may be required in combination with sildenafil to achieve safe therapeutic plasma concentrations and reduce the risk of potential toxicity, but it is not necessary for co-administration with macitentan.

N-methyl-D-aspartate receptors and thymoquinone induce apoptosis and alteration in mitochondria in colorectal cancer cells.

Colon cancer is on the rise in both men and women. In addition to traditional treatment methods, herbal treatments from complementary and alternative medicine are actively followed. Naturally derived from plants, thymoquinone (TQ) has drawn a lot of attention in the field of cancer treatment. MK-801, an N-methyl-D-aspartate agonist, is used to improve memory and plasticity, but it has also lately been explored as a potential cancer treatment. This study aimed to determine the roles of N-Methyl-D-Aspartate agonists and Thymoquinone on mitochondria and apoptosis. HT-29 cells were treated with different TQ and MK-801 concentrations. We analyzed cell viability, apoptosis, and alteration of mitochondria. Cell viability significantly decreased depending on doses of TQ and MK-801. Apoptosis and mitochondrial dysfunctions induced by low and high doses of TQ and MK-801. Our study emphasizes the need for further safety evaluation of MK-801 due to the potential toxicity risk of TQ and MK-801. Optimal and toxic doses of TQ and MK-801 were determined for the treatment of colon cancer. It should be considered as a possibility that colon cancer can be treated with TQ and MK-801.

Potential Toxic Metal Concentration and Risk Assessment in Agricultural Soil and Lentil Crop (Lens culinaris Medik) in Dawunt Woreda, Northwest Wollo, Ethiopia.

Health implications for the population due to consuming contaminated crops have been a great concern worldwide. This study aimed to measure the levels of potential toxic elements in lentils and their growing soil in Dawunt Woreda, Ethiopia. Accordingly, 15 soil samples along with the lentil samples were collected to measure the level of potential toxic elements, including chromium (Cr), manganese (Mn), iron (Fe), lead (Pb), cadmium (Cd), copper (Cu), and cobalt (Co), by using an inductively coupled plasma optical emission spectrometer and for assessing the potential ecological and human health risk. The wet digestion method using aqua regia (HCl/HNO3 3 : 1) was employed for soil and lentil sample preparation. The mean concentrations of Fe, Mn, Co, Cu, Cd, Pb, and Cr in the lentil sample were 60.4, 9.68, 0.75, 5.7, 0.25, 0.9, and 1.15 mg/kg, respectively. In soil, the mean concentrations of Fe, Mn, Co, Cu, Cd, Pb, and Cr were 649, 19.9, 3.32, 40.0, 15.2, 1.83, and 69.1 mg/kg, respectively. All of the potential toxic metals in agricultural soil and lentil samples were found to be below the reference level set by the World Health Organization, except Cd, in the soil samples. Five single metal and three cumulative pollution index parameters were employed for the data and results showed that Fe, Cu, and Cr moderately pollute the soil and are highly contaminated by Cd. The cumulative pollution indices also confirmed that the extent of soil pollution varied from highly contaminated to moderate contamination. The possible health risks at various exposure routes have also been estimated. The single-metal and cumulative-metals health risks (cancer and noncancer) of adults and children due to chronic exposure to soil and consumption of lentils were estimated using the health quotient and health index values as per the United States Environmental Protection Agency guidelines. Thus, the results revealed no significant adverse health risks (cancer and noncancer) for adults and children. Therefore, the inhabitants in the study area have no significant health impacts due to either the consumption of lentil crops or exposure to agricultural soil particles.

Assessment of drug utilization and potentially inappropriate medications in hemodialysis patients with end-stage renal dysfunction: A study in a tertiary care hospital in Bahrain.

Patients undergoing dialysis pose therapeutic challenges in terms of polypharmacy, administration of potentially inappropriate drugs, and drugs with the potential risk of toxicity. This study evaluated the use of drugs, potentially inappropriate medicines (PIM), drugs with risk of Torsades de Pointes (TdP), and the complexity of the prescribed regimen using the medication regimen complexity index scale in patients undergoing hemodialysis. A retrospective cohort study was carried out amongst patients receiving hemodialysis. Drugs were classified into one of four classes: (i) drugs used in managing renal complications, (ii) cardiovascular drugs, (iii) anti-diabetic drugs, (iv) drugs for symptomatic management, and (v) others. Drugs were considered as PIM according to the Can-SOLVE CKD working group from a network of Canadian nephrology health professionals. The study adhered to the CredibleMeds classification of drugs with known, possible, and conditional risk of TdP and the complexity of prescribed medicines was evaluated based on the pre-validated medication regimen complexity index scale based on form/route, frequency of dosing, and requirement of special instructions. Sixty-three participants were included in the study (49 males and 14 females) with the median (range) age of 45 (21-66) years. Cardiovascular drugs followed by drugs used for managing renal complications were the most common classes administered. Notably, 12 (19.1%) patients received one of the non-steroidal anti-inflammatory drugs, 21 (33.3%) received a proton pump inhibitor, three (4.8%) received pregabalin, two (3.2%) received opioid drugs, and one (1.6%) was administered celecoxib. Atorvastatin, furosemide, omeprazole, and allopurinol were the most common PIM drugs administered to the study participants followed by others. Drugs used for symptomatic management had significantly more PIM compared to other classes (p <0.0001). Six (9.5%) patients received drugs with known TdP risk, one with possible TdP risk, and 61 with conditional risk. Median (range) medical regimen complexity index score was 26.5 (2-62.5). A huge burden of drug therapy was observed in the hemodialysis patients in terms of higher proportions of PIM, complex medical regimen, and prescription of drugs with risk of TdP. Implementation of clinical decision support tools enhancing rational prescription and identification of drugs with TdP risk, introducing antimicrobial stewardship, and stepwise deprescription of the drugs with the least benefit-risk ratio are warranted.

Sustained release local anesthetics for pain management: relevance and formulation approaches.

This review attempted to ascertain the rationale for the formulation of sustained-release local anesthetics and summarize the various formulation approaches designed to date to achieve sustained and localized local analgesic effects. The incidence of pain, which is the concern of patients as well as health care professionals, is increasing due to accidents, surgical procedures, and other diseases. Local anesthetics can be used for the management of moderate to severe acute and chronic pain. They also allow regional analgesia, in situations where the cause and source of the pain are limited to a particular site or region, without the need for loss of consciousness or systemic administration of other analgesics thereby decreasing the risk of potential toxicities. Though they have an interesting antipain efficacy, the short duration of action of local anesthetics makes the need for their multiple injections or opioid adjuvants mandatory. To overcome this problem, different formulations are being designed that help achieve prolonged analgesia with a single dose of administration. Combination with adjuvants, liposomal formulations, lipid-based nanoparticles, thermo-responsive nanogels, microspheres, microcapsules, complexation with multivalent counterions and HP-β-CD, lipid-based nanoparticles, and bio-adhesive films, and polymeric matrices are among the approaches. Further safety studies are required to ensure the safe and effective utilization of sustained-release local anesthetics. Moreover, the release kinetics of the various formulations should be adequately established.