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Volume 12, September
 
 

J. Xenobiot., Volume 12, Issue 4 (December 2022) – 9 articles

Cover Story (view full-size image): Xenobiotics and their metabolism in the human body have been researched for many years already. Especially in pharmacotherapy, there is great interest in gaining knowledge about metabolism and elimination of drugs. Drugs can cause inhibition or induction of the metabolizing enzymes leading to a change in serum concentrations of victim drugs. Therefore, the knowledge of the pharmacokinetic properties of the drugs is important to be able to avoid drug interactions. In recent years, new lessons have been learned: the pharmacogenetic profile of the patients in regard to the liver enzymes has a large impact on pharmacokinetics and drug interactions. With the knowledge of pharmacokinetic profiles of the drugs and the pharmacogenetic profile of the patient, healthcare providers can individualize drug therapy. View this paper
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28 pages, 11714 KiB  
Review
Chemotherapeutic Potential of Saikosaponin D: Experimental Evidence
by Suryaa Manoharan, Bhuvaneshwari Deivendran and Ekambaram Perumal
J. Xenobiot. 2022, 12(4), 378-405; https://doi.org/10.3390/jox12040027 - 17 Dec 2022
Cited by 6 | Viewed by 2783
Abstract
Saikosaponin D (SSD), an active compound derived from the traditional plant Radix bupleuri, showcases potential in disease management owing to its antioxidant, antipyretic, and anti-inflammatory properties. The toxicological effects of SSD mainly include hepatotoxicity, neurotoxicity, hemolysis, and cardiotoxicity. SSD exhibits antitumor effects [...] Read more.
Saikosaponin D (SSD), an active compound derived from the traditional plant Radix bupleuri, showcases potential in disease management owing to its antioxidant, antipyretic, and anti-inflammatory properties. The toxicological effects of SSD mainly include hepatotoxicity, neurotoxicity, hemolysis, and cardiotoxicity. SSD exhibits antitumor effects on multiple targets and has been witnessed in diverse cancer types by articulating various cell signaling pathways. As a result, carcinogenic processes such as proliferation, invasion, metastasis, and angiogenesis are inhibited, whereas apoptosis, autophagy, and differentiation are induced in several cancer cells. Since it reduces side effects and strengthens anti-cancerous benefits, SSD has been shown to have an additive or synergistic impact with chemo-preventive medicines. Regardless of its efficacy and benefits, the considerations of SSD in cancer prevention are absolutely under-researched due to its penurious bioavailability. Diverse studies have overcome the impediments of inadequate bioavailability using nanotechnology-based methods such as nanoparticle encapsulation, liposomes, and several other formulations. In this review, we emphasize the association of SSD in cancer therapeutics and the discussion of the mechanisms of action with the significance of experimental evidence. Full article
(This article belongs to the Section Natural Products/Herbal Medicines)
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13 pages, 590 KiB  
Communication
Uses of Antibiotics in Ornamental Fish in Hong Kong and the Antibiotic Resistance in the Associated Zoonotic Pathogens
by Chun Au-Yeung, Kit-Ling Lam, Ka-Wai Chan and Wing-Yin Mo
J. Xenobiot. 2022, 12(4), 365-377; https://doi.org/10.3390/jox12040026 - 04 Dec 2022
Viewed by 2636
Abstract
The use of antibiotics in ornamental fish is not regulated, as they are not intended for human consumption. Although antibiotic resistant bacteria have been detected in ornamental fish worldwide, there have been no studies to look at the situation in Hong Kong. Therefore, [...] Read more.
The use of antibiotics in ornamental fish is not regulated, as they are not intended for human consumption. Although antibiotic resistant bacteria have been detected in ornamental fish worldwide, there have been no studies to look at the situation in Hong Kong. Therefore, the present study was conducted to investigate the use of antibiotics in ornamental fish. Ornamental fish were purchased from five local pet fish shops and the antibiotics in carriage water were quantified using liquid chromatography tandem mass spectrometry. Moreover, Aeromonas and Pseudomonas spp. present in carriage water were isolated and their minimum inhibitory concentrations against selected antibiotics were determined. Results indicated that among the twenty antibiotics screened, doxycycline (0.0155–0.0836 µg L−1), oxytetracycline (0.0102–29.0 µg L−1), tetracycline (0.0350–0.244 µg L−1), enrofloxacin (0.00107–0.247 µg L−1), and oxalinic acid (n.d.−0.514 µg L−1) were detected in all sampled shops. Additionally, MIC results revealed that some of the Aeromonas and Pseudomonas spp. isolates were highly resistant to all antibiotics selected. Our findings confirmed that multiple antibiotics are being used in ornamental fish and the associated bacteria are resistant to selected antibiotics, suggesting that this could be a significant transmission route of antibiotic resistant bacteria to household indoor environments. Full article
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9 pages, 1184 KiB  
Article
Application of Fabric Phase Sorptive Extraction (FPSE) Engaged to Tandem LC-MS/MS for Quantification of Brorphine in Oral Fluid
by Dimitra Florou, Thalia Vlachou, Vasilios Sakkas and Vassiliki Boumba
J. Xenobiot. 2022, 12(4), 356-364; https://doi.org/10.3390/jox12040025 - 25 Nov 2022
Cited by 1 | Viewed by 1731
Abstract
Brorphine (1-[1-[1-(4-bromophenyl) ethyl]-piperidin-4-yl]-1,3-dihydro-2H-benzo [d]imidazol-2-one) is one of the most recent novel synthetic opioids (NSOs) on the novel psychoactive substances (NPSs) market, involved in over 100 deaths in 2020. Brorphine is a substituted piperidine-benzimidazolone analogue that retains structural similarities to fentanyl, acting as a [...] Read more.
Brorphine (1-[1-[1-(4-bromophenyl) ethyl]-piperidin-4-yl]-1,3-dihydro-2H-benzo [d]imidazol-2-one) is one of the most recent novel synthetic opioids (NSOs) on the novel psychoactive substances (NPSs) market, involved in over 100 deaths in 2020. Brorphine is a substituted piperidine-benzimidazolone analogue that retains structural similarities to fentanyl, acting as a full agonist at the μ-opioid receptor. Oral Fluid (OF) is an alternative matrix, frequently analyzed for the detection of NPS. Fabric phase sorptive extraction (FPSE) is a superior, green-sample -preparation technology recently applied for drug analysis. This contribution presents the development and validation of a method, based on the application of FPSE and liquid chromatography–tandem mass spectrometry (LC-MS/MS), to determine/quantitate brorphine in OF. The method’s linearity ranged between 0.05 and 50 ng/mL (R2 = 0.9993), the bias ranged between 12.0 and 16.8%, and inter- and intra-day precisions ranged between 6.4 and 9.9%. Accuracy and extraction efficiency lied between 65 and 75%. LOD/LOQ were 0.015 ng/mL/0.05 ng/mL. Analyte’s post-preparative stability was higher than 95%, while no matrix interferences and carryover between runs were observed. This is the first report introducing the application of FPSE for NPS determination, specifically, the quantification of brorphine in OF, thereby presenting a simple, rapid, sensitive, specific, effective, and reliable procedure engaged to LC-MS/MS that is suitable for routine application and the analysis of more NPSs. Full article
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12 pages, 797 KiB  
Review
Xeno-Estrogenic Pesticides and the Risk of Related Human Cancers
by Vivek Kumar, Chandra Shekhar Yadav and Basu Dev Banerjee
J. Xenobiot. 2022, 12(4), 344-355; https://doi.org/10.3390/jox12040024 - 21 Nov 2022
Cited by 2 | Viewed by 3877
Abstract
In recent decades, “environmental xenobiotic-mediated endocrine disruption”, especially by xeno-estrogens, has gained a lot of interest from toxicologists and environmental researchers. These estrogen-mimicking chemicals are known to cause various human disorders. Pesticides are the most heavily used harmful xenobiotic chemicals around the world. [...] Read more.
In recent decades, “environmental xenobiotic-mediated endocrine disruption”, especially by xeno-estrogens, has gained a lot of interest from toxicologists and environmental researchers. These estrogen-mimicking chemicals are known to cause various human disorders. Pesticides are the most heavily used harmful xenobiotic chemicals around the world. The estrogen-mimicking potential of the most widely used organochlorine pesticides is well established. However, their effect is not as clearly understood among the plethora of effects these persistent xenobiotics are known to pose on our physiological system. Estrogens are one of the principal risk modifiers of various disorders, including cancer, not only in women but in men as well. Despite the ban on these xenobiotics in some parts of the world, humans are still at apparent risk of exposure to these harmful chemicals as they are still widely persistent and likely to stay in our environment for a long time owing to their high chemical stability. The present work intends to understand how these harmful chemicals may affect the risk of the development of estrogen-mediated human cancer. Full article
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15 pages, 2581 KiB  
Article
An Ecological Approach to Control Pathogens of Lycopersicon esculentum L. by Slow Release of Mancozeb from Biopolymeric Conjugated Nanoparticles
by Ravinder Kumar, Vikash Nain and Joginder Singh Duhan
J. Xenobiot. 2022, 12(4), 329-343; https://doi.org/10.3390/jox12040023 - 09 Nov 2022
Cited by 3 | Viewed by 1886
Abstract
To control insects, weeds, and infections in crops, old-fashioned pesticide formulations (with massive quantities of heavy metals and a variety of chemicals) are used. By biological amplification via the food chain, many of these established pesticide formulations have accumulated in living systems and [...] Read more.
To control insects, weeds, and infections in crops, old-fashioned pesticide formulations (with massive quantities of heavy metals and a variety of chemicals) are used. By biological amplification via the food chain, many of these established pesticide formulations have accumulated in living systems and caused environmental pollution. To form a nanoparticulate matrix with a diameter ranging from 322.2 ± 0.9 to 403.7 ± 0.7 nm, mancozeb was embedded in chitosan–gum acacia (CSGA) biopolymers and loadings were confirmed via TEM and FTIR. Differential scanning calorimetry analyses were carried out as part of the investigation. Inhibition of Alternaria alternata by nanoparticles (NPs) with 1.0 mg/mL mancozeb (CSGA-1.0) was 85.2 ± 0.7 % at 0.5 ppm, whereas for Stemphylium lycopersici it was 62.1 ± 0.7% in the mycelium inhibition method. NPs demonstrated antimicrobial action in pot house environments. After ten hours, the mancozeb was liberated from the nanoformulations due to polymer matrix diffusion and relaxation, compared to 2 h for commercial mancozeb. Even while drug-loaded conjugated nanoparticles have equivalent antifungal activities, they have a lower release rate and, hence, reduced toxicology compared to commercial mancozeb. Therefore, this method can be employed to implement sustainable farming techniques in the future. Full article
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12 pages, 1399 KiB  
Article
Rates of Divergent Pharmacogenes in a Psychiatric Cohort of Inpatients with Depression—Arguments for Preemptive Testing
by Sibylle Christine Roll and Martina Hahn
J. Xenobiot. 2022, 12(4), 317-328; https://doi.org/10.3390/jox12040022 - 28 Oct 2022
Cited by 2 | Viewed by 1800
Abstract
Background: The international drug agencies annotate pharmacogenes for many years. Pharmacogenetic testing is thus far only established in few settings, assuming that only few patients are actually affected by drug-gene interactions. Methods: 108 hospitalized patients with major depressive disorder were genotyped for CYP1A2 [...] Read more.
Background: The international drug agencies annotate pharmacogenes for many years. Pharmacogenetic testing is thus far only established in few settings, assuming that only few patients are actually affected by drug-gene interactions. Methods: 108 hospitalized patients with major depressive disorder were genotyped for CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, NAT2, DPYD; VKORC1 and TMTP. Results: We found 583 (mean 5.4, median 5) divergent phenotypes (i.e., divergent from the common phenotypes considered normal, e.g., extensive metabolizer) in the 12 analyzed pharmacokinetic genes. The rate for at least one divergent phenotype was 100% in our cohort for CYP, but also for all 12 important pharmacogenes: patients had at least two divergent phenotypes. Compared to a large Danish cohort, CYP2C9 NM and IM status, CYP2C19 UM, CYP2D6 UM and DYPD (GAS 0, 1, 2) genotypes differed statistical significantly. For CYP2D6 and CYP2C19, 13% of the patients were normal metabolizers for both enzymes in our cohort, but this value was 27.3% in the Danish cohort, which is a highly significant difference (p < 0.0001). Conclusion: Divergent phenotypes in pharmacogenes are not the exception, but the rule. Patients with divergent phenotypes seem more prone for hospitalization, emphasizing the need for pre-emptive testing to avoid inefficacy and adverse drug effects in all patients. Full article
(This article belongs to the Topic Hazard Assessment of Endocrine Disrupting Chemicals)
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10 pages, 894 KiB  
Article
The Effects of Chromium and Vanadium on Biomarkers of Carbohydrate and Lipid Metabolism in Workers Exposed to Coal Fly Ash
by Lulzim Zeneli, Majlinda Daci-Ajvazi, Ankica Sekovanić, Jasna Jurasović and Demush Bajraktari
J. Xenobiot. 2022, 12(4), 307-316; https://doi.org/10.3390/jox12040021 - 19 Oct 2022
Viewed by 2146
Abstract
Chromium (Cr) and vanadium (V) are micronutrients playing a role in carbohydrate and lipid metabolism but can be toxic at high concentrations, especially in specific forms. The study documents the effect of Cr and V concentrations on glucose and lipid metabolism in workers [...] Read more.
Chromium (Cr) and vanadium (V) are micronutrients playing a role in carbohydrate and lipid metabolism but can be toxic at high concentrations, especially in specific forms. The study documents the effect of Cr and V concentrations on glucose and lipid metabolism in workers exposed to coal fly ash. We quantified selected metals (Cr, V) in the blood and serum of workers from a thermal power plant in Kosovo and compared them with the reference biological values. We determined fasting serum glucose and lipid profiles using a biochemical analyzer Synchron CX7 (Beckman Coulter). We quantified blood and serum Cr and V by inductively coupled plasma mass spectrometry. We also evaluated the association between carbohydrate and lipid metabolism biomarkers (glucose, cholesterol, and triglycerides) and co-exposure to coal fly ash. Power plant workers had significantly higher blood Cr and V levels (p < 0.0001) and significantly lower serum Cr and V levels (p < 0.0001) than the controls. We also found statistically significant (p < 0.0001) correlations between high blood Cr levels and low glucose/blood Cr ratios as well as between high serum Cr levels and low glucose/serum Cr ratios. Finally, in power plant workers, high blood V levels significantly correlated with low triglycerides/blood V and cholesterol/blood V ratios (p < 0.0001), while high serum V levels correlated with low cholesterol/serum V ratios (p = 0.005). Based on these findings, we concluded that the glucose/Cr, triglycerides/V and cholesterol/V ratios should be considered when evaluating carbohydrate and lipid metabolism disorders in occupationally-exposed workers. Full article
(This article belongs to the Section Ecotoxicology)
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18 pages, 2373 KiB  
Review
Antiviral and Anti-Inflammatory Plant-Derived Bioactive Compounds and Their Potential Use in the Treatment of COVID-19-Related Pathologies
by Purvi Trivedi, Amna Abbas, Christian Lehmann and H. P. Vasantha Rupasinghe
J. Xenobiot. 2022, 12(4), 289-306; https://doi.org/10.3390/jox12040020 - 08 Oct 2022
Cited by 9 | Viewed by 3956
Abstract
The highly contagious coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic and public health emergency as it has taken the lives of over 5.7 million in more than 180 different countries. This disease [...] Read more.
The highly contagious coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic and public health emergency as it has taken the lives of over 5.7 million in more than 180 different countries. This disease is characterized by respiratory tract symptoms, such as dry cough and shortness of breath, as well as other symptoms, including fever, chills, and fatigue. COVID-19 is also characterized by the excessive release of cytokines causing inflammatory injury to the lungs and other organs. It is advised to undergo precautionary measures, such as vaccination, social distancing, use of masks, hygiene, and a healthy diet. This review is aimed at summarizing the pathophysiology of COVID-19 and potential biologically active compounds (bioactive) found in plants and plant food. We conclude that many plant food bioactive compounds exhibit antiviral and anti-inflammatory properties and support in attenuating organ damage due to reduced cytokine release and improving the recovery process from COVID-19 infection. Full article
(This article belongs to the Section Natural Products/Herbal Medicines)
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23 pages, 1593 KiB  
Review
Narrative Review: Glucocorticoids in Alcoholic Hepatitis—Benefits, Side Effects, and Mechanisms
by Hong Lu
J. Xenobiot. 2022, 12(4), 266-288; https://doi.org/10.3390/jox12040019 - 21 Sep 2022
Cited by 5 | Viewed by 2853
Abstract
Alcoholic hepatitis is a major health and economic burden worldwide. Glucocorticoids (GCs) are the only first-line drugs recommended to treat severe alcoholic hepatitis (sAH), with limited short-term efficacy and significant side effects. In this review, I summarize the major benefits and side effects [...] Read more.
Alcoholic hepatitis is a major health and economic burden worldwide. Glucocorticoids (GCs) are the only first-line drugs recommended to treat severe alcoholic hepatitis (sAH), with limited short-term efficacy and significant side effects. In this review, I summarize the major benefits and side effects of GC therapy in sAH and the potential underlying mechanisms. The review of the literature and data mining clearly indicate that the hepatic signaling of glucocorticoid receptor (GR) is markedly impaired in sAH patients. The impaired GR signaling causes hepatic down-regulation of genes essential for gluconeogenesis, lipid catabolism, cytoprotection, and anti-inflammation in sAH patients. The efficacy of GCs in sAH may be compromised by GC resistance and/or GC’s extrahepatic side effects, particularly the side effects of intestinal epithelial GR on gut permeability and inflammation in AH. Prednisolone, a major GC used for sAH, activates both the GR and mineralocorticoid receptor (MR). When GC non-responsiveness occurs in sAH patients, the activation of MR by prednisolone might increase the risk of alcohol abuse, liver fibrosis, and acute kidney injury. To improve the GC therapy of sAH, the effort should be focused on developing the biomarker(s) for GC responsiveness, liver-targeting GR agonists, and strategies to overcome GC non-responsiveness and prevent alcohol relapse in sAH patients. Full article
(This article belongs to the Section Drug Therapeutics)
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