Journal of Xenobiotics

14 pages, 2482 KiB

Open AccessArticle

Development of a Dynamic Network Model to Identify Temporal Patterns of Structural Malformations in Zebrafish Embryos Exposed to a Model Toxicant, Tris(4-chlorophenyl)methanol

by Ashley V. Schwartz, Karilyn E. Sant and Uduak Z. George

J. Xenobiot. 2023, 13(2), 284-297; https://doi.org/10.3390/jox13020021 - 16 Jun 2023

Viewed by 1511

Abstract

Embryogenesis is a well-coordinated process relying on precise cues and environmental signals that direct spatiotemporal embryonic patterning. Quite often, when one error in this process occurs, others tend to co-occur. We posit that investigating the co-occurrence of these abnormalities over time would yield [...] Read more.

Embryogenesis is a well-coordinated process relying on precise cues and environmental signals that direct spatiotemporal embryonic patterning. Quite often, when one error in this process occurs, others tend to co-occur. We posit that investigating the co-occurrence of these abnormalities over time would yield additional information about the mode of toxicity for chemicals. Here, we use the environmental contaminant tris(4-chlorophenyl)methanol (TCPMOH) as a model toxicant to assess the relationship between exposures and co-occurrence of developmental abnormalities in zebrafish embryos. We propose a dynamic network modeling approach to study the co-occurrence of abnormalities, including pericardial edema, yolk sac edema, cranial malformation, spinal deformity, delayed/failed swim bladder inflation, and mortality induced by TCPMOH exposure. TCPMOH-exposed samples revealed increased abnormality co-occurrence when compared to controls. The abnormalities were represented as nodes in the dynamic network model. Abnormalities with high co-occurrence over time were identified using network centrality scores. We found that the temporal patterns of abnormality co-occurrence varied between exposure groups. In particular, the high TCPMOH exposure group experienced abnormality co-occurrence earlier than the low exposure group. The network model also revealed that pericardial and yolk sac edema are the most common critical nodes among all TCPMOH exposure levels, preceding further abnormalities. Overall, this study introduces a dynamic network model as a tool for assessing developmental toxicology, integrating structural and temporal features with a concentration response. Full article

(This article belongs to the Section Emerging Chemicals)

► Show Figures

Figure 1

14 pages, 3334 KiB

Open AccessArticle

Evaluation of Cytotoxicity, Release Behavior and Phytopathogens Control by Mancozeb-Loaded Guar Gum Nanoemulsions for Sustainable Agriculture

by Ravinder Kumar, Manju Nehra, Dharmender Kumar, Baljeet Singh Saharan, Prince Chawla, Pardeep Kumar Sadh, Anju Manuja and Joginder Singh Duhan

J. Xenobiot. 2023, 13(2), 270-283; https://doi.org/10.3390/jox13020020 - 05 Jun 2023

Cited by 1 | Viewed by 1871

Abstract

Chemical fungicides are the backbone of modern agriculture, but an alternative formulation is necessary for sustainable crop production to address human health issues and soil/water environmental pollution. So, a green chemistry approach was used to form guar gum nanoemulsions (NEs) of 186.5–394.1 nm [...] Read more.

Chemical fungicides are the backbone of modern agriculture, but an alternative formulation is necessary for sustainable crop production to address human health issues and soil/water environmental pollution. So, a green chemistry approach was used to form guar gum nanoemulsions (NEs) of 186.5–394.1 nm containing the chemical fungicide mancozeb and was characterized using various physio-chemical techniques. An 84.5% inhibition was shown by 1.5 mg/mL mancozeb-loaded NEs (GG-1.5) against A. alternata, comparable to commercial mancozeb (86.5 ± 0.7%). The highest mycelial inhibition was exhibited against S. lycopersici and S. sclerotiorum. In tomatoes and potatoes, NEs showed superior antifungal efficacy in pot conditions besides plant growth parameters (germination percentage, root/shoot ratio and dry biomass). About 98% of the commercial mancozeb was released in just two h, while only about 43% of mancozeb was released from nanoemulsions (0.5, 1.0 and 1.5) for the same time. The most significant results for cell viability were seen at 1.0 mg/mL concentration of treatment, where wide gaps in cell viability were observed for commercial mancozeb (21.67%) and NEs treatments (63.83–71.88%). Thus, this study may help to combat the soil and water pollution menace of harmful chemical pesticides besides protecting vegetable crops. Full article

(This article belongs to the Section Nanotoxicology and Nanopharmacology)

► Show Figures

Figure 1

18 pages, 1537 KiB

Open AccessReview

Microbe-Plant Interactions Targeting Metal Stress: New Dimensions for Bioremediation Applications

by Baljeet Singh Saharan, Twinkle Chaudhary, Balwan Singh Mandal, Dharmender Kumar, Ravinder Kumar, Pardeep Kumar Sadh and Joginder Singh Duhan

J. Xenobiot. 2023, 13(2), 252-269; https://doi.org/10.3390/jox13020019 - 01 Jun 2023

Cited by 1 | Viewed by 2052

Abstract

In the age of industrialization, numerous non-biodegradable pollutants like plastics, HMs, polychlorinated biphenyls, and various agrochemicals are a serious concern. These harmful toxic compounds pose a serious threat to food security because they enter the food chain through agricultural land and water. Physical [...] Read more.

In the age of industrialization, numerous non-biodegradable pollutants like plastics, HMs, polychlorinated biphenyls, and various agrochemicals are a serious concern. These harmful toxic compounds pose a serious threat to food security because they enter the food chain through agricultural land and water. Physical and chemical techniques are used to remove HMs from contaminated soil. Microbial-metal interaction, a novel but underutilized strategy, might be used to lessen the stress caused by metals on plants. For reclaiming areas with high levels of heavy metal contamination, bioremediation is effective and environmentally friendly. In this study, the mechanism of action of endophytic bacteria that promote plant growth and survival in polluted soils—known as heavy metal-tolerant plant growth-promoting (HMT-PGP) microorganisms—and their function in the control of plant metal stress are examined. Numerous bacterial species, such as Arthrobacter, Bacillus, Burkholderia, Pseudomonas, and Stenotrophomonas, as well as a few fungi, such as Mucor, Talaromyces, Trichoderma, and Archaea, such as Natrialba and Haloferax, have also been identified as potent bioresources for biological clean-up. In this study, we additionally emphasize the role of plant growth-promoting bacteria (PGPB) in supporting the economical and environmentally friendly bioremediation of heavy hazardous metals. This study also emphasizes future potential and constraints, integrated metabolomics approaches, and the use of nanoparticles in microbial bioremediation for HMs. Full article

► Show Figures

Figure 1

15 pages, 4562 KiB

Open AccessArticle

Transcriptional Alterations Induced by Delta-9 Tetrahydrocannabinol in the Brain and Gonads of Adult Medaka

by Marlee Vassall, Sourav Chakraborty, Yashi Feng, Mehwish Faheem, Xuegeng Wang and Ramji Kumar Bhandari

J. Xenobiot. 2023, 13(2), 237-251; https://doi.org/10.3390/jox13020018 - 30 May 2023

Viewed by 1457

Abstract

With the legalization of marijuana smoking in several states of the United States and many other countries for medicinal and recreational use, the possibility of its release into the environment cannot be overruled. Currently, the environmental levels of marijuana metabolites are not monitored [...] Read more.

With the legalization of marijuana smoking in several states of the United States and many other countries for medicinal and recreational use, the possibility of its release into the environment cannot be overruled. Currently, the environmental levels of marijuana metabolites are not monitored on a regular basis, and their stability in the environment is not well understood. Laboratory studies have linked delta 9-tetrahydrocannabinol (Δ⁹-THC) exposure with behavioral abnormalities in some fish species; however, their effects on endocrine organs are less understood. To understand the effects of THC on the brain and gonads, we exposed adult medaka (Oryzias latipes, Hd-rR strain, both male and female) to 50 ug/L THC for 21 days spanning their complete spermatogenic and oogenic cycles. We examined transcriptional responses of the brain and gonads (testis and ovary) to Δ⁹-THC, particularly molecular pathways associated with behavioral and reproductive functions. The Δ⁹-THC effects were more profound in males than females. The Δ⁹-THC-induced differential expression pattern of genes in the brain of the male fish suggested pathways to neurodegenerative diseases and pathways to reproductive impairment in the testis. The present results provide insights into endocrine disruption in aquatic organisms due to environmental cannabinoid compounds. Full article

(This article belongs to the Special Issue Environmental Toxicology and Animal Health)

► Show Figures

Figure 1

19 pages, 769 KiB

Open AccessEditor’s ChoiceSystematic Review

Systematic Review of Safety of Selective Androgen Receptor Modulators in Healthy Adults: Implications for Recreational Users

by Jonathan D. Vignali, Kevin C. Pak, Holly R. Beverley, Jesse P. DeLuca, John W. Downs, Adrian T. Kress, Brett W. Sadowski and Daniel J. Selig

J. Xenobiot. 2023, 13(2), 218-236; https://doi.org/10.3390/jox13020017 - 10 May 2023

Cited by 13 | Viewed by 6986

Abstract

Selective Androgen Receptor Modulators (SARMs) are not FDA approved, and obtaining SARMs for personal use is illegal. Nevertheless, SARM use is increasingly popular amongst recreational athletes. Recent case reports of drug-induced liver injury (DILI) and tendon rupture raise serious concerns for the safety [...] Read more.

Selective Androgen Receptor Modulators (SARMs) are not FDA approved, and obtaining SARMs for personal use is illegal. Nevertheless, SARM use is increasingly popular amongst recreational athletes. Recent case reports of drug-induced liver injury (DILI) and tendon rupture raise serious concerns for the safety of recreational SARM users. On 10 November 2022 PubMed, Scopus, Web of Science, and ClinicalTrials.gov were searched for studies that reported safety data of SARMs. A multi-tiered screening approach was utilized, and any study or case report of generally healthy individuals exposed to any SARM was included. Thirty-three studies were included in the review with 15 case reports or case series and 18 clinical trials (total patients N = 2136 patients, exposed to SARM N = 1447). There were case reports of drug-induced liver injury (DILI) (N = 15), Achilles tendon rupture (N = 1), rhabdomyolysis (N = 1), and mild reversible liver enzyme elevation (N = 1). Elevated alanine aminotransferase (ALT) was commonly reported in clinical trials in patients exposed to SARM (mean 7.1% across trials). Two individuals exposed to GSK2881078 in a clinical trial were reported to have rhabdomyolysis. Recreational SARM use should be strongly discouraged, and the risks of DILI, rhabdomyolysis, and tendon rupture should be emphasized. However, despite warnings, if a patient refuses to discontinue SARM use, ALT monitoring or dose reduction may improve early detection and prevention of DILI. Full article

(This article belongs to the Section Drug Therapeutics)

► Show Figures

Figure 1

13 pages, 1173 KiB

Open AccessArticle

Incubation Time Influences Organic Anion Transporter 1 Kinetics and Renal Clearance Predictions

by Aaron O. Buaben and Ryan M. Pelis

J. Xenobiot. 2023, 13(2), 205-217; https://doi.org/10.3390/jox13020016 - 10 May 2023

Viewed by 1626

Abstract

Accurate predictions of drug uptake transporter involvement in renal excretion of xenobiotics require determination of in vitro transport kinetic parameters under initial-rate conditions. The purpose of the present study was to determine how changing the incubation time from initial rate to steady state [...] Read more.

Accurate predictions of drug uptake transporter involvement in renal excretion of xenobiotics require determination of in vitro transport kinetic parameters under initial-rate conditions. The purpose of the present study was to determine how changing the incubation time from initial rate to steady state influences ligand interactions with the renal organic anion transporter 1 (OAT1), and the impact of the different experimental conditions on pharmacokinetic predictions. Transport studies were performed with Chinese hamster ovary cells expressing OAT1 (CHO-OAT1) and the Simcyp Simulator was used for physiological-based pharmacokinetic predictions. Maximal transport rate and intrinsic uptake clearance (CL_int) for PAH decreased with increasing incubation time. The CL_int values ranged 11-fold with incubation times spanning from 15 s (CL_int,15s, initial rate) to 45 min (CL_int,45min, steady state). The Michaelis constant (K_m) was also influenced by the incubation time with an apparent increase in the Km value at longer incubation times. Inhibition potency of five drugs against PAH transport was tested using incubation times of either 15 s or 10 min. There was no effect of time on inhibition potency for omeprazole or furosemide, whereas indomethacin was less potent, and probenecid (~2-fold) and telmisartan (~7-fold) more potent with the longer incubation time. Notably, the inhibitory effect of telmisartan was reversible, albeit slowly. A pharmacokinetic model was developed for PAH using the CL_int,15s value. The simulated plasma concentration-time profile, renal clearance, and cumulative urinary excretion-time profile of PAH agreed well with reported clinical data, and the PK parameters were sensitive to the time-associated CL_int value used in the model. Full article

(This article belongs to the Section Drug Therapeutics)

► Show Figures

Figure 1

12 pages, 295 KiB

Open AccessArticle

Correlation of Vitamin 25(OH)D, Liver Enzymes, Potassium, and Oxidative Stress Markers with Lipid Profile and Atheromatic Index: A Pilot Study

by Stavroula Ioannidou, Konstantina Kazeli, Hristos Ventouris, Dionysia Amanatidou, Argyrios Gkinoudis and Evgenia Lymperaki

J. Xenobiot. 2023, 13(2), 193-204; https://doi.org/10.3390/jox13020015 - 01 Apr 2023

Viewed by 2063

Abstract

According to recent literature, there is a limited amount of data about the correlation of vitamin 25(OH)D, potassium (K), oxidative stress parameters, and other biomarkers with dyslipidemia, which is an established risk factor for cardiovascular diseases (CVDs). This study aims to investigate the [...] Read more.

According to recent literature, there is a limited amount of data about the correlation of vitamin 25(OH)D, potassium (K), oxidative stress parameters, and other biomarkers with dyslipidemia, which is an established risk factor for cardiovascular diseases (CVDs). This study aims to investigate the correlation of lipid profile and atheromatic index TC/HDL with several biomarkers and oxidative stress parameters. A total of 102 volunteers, 67 with atheromatic index TC/HDL > 3.5 (Group A) and 35 with TC/HDL < 3.5 (Group B), aged from 26 to 78 years, participated in this study. Serum levels of triglycerides (TG), total cholesterol (TC), low- and high-density lipoproteins (LDL and HDL), vitamin 25(OH)D [25(OH)D], potassium (K), sodium (Na), lactose dehydrogenase (LDH), liver enzymes including serum glutamic oxaloacetic and glutamic pyruvic transaminases (SGOT and SGPT), gamma-glutamyl transferase (γ-GT), and alkaline phosphatase (ALP) were analyzed using standard photometric methods. Oxidative stress parameters such as reactive oxygen species (ROS) were detected with fluorometric methods, whereas total oxidative (TOS) and antioxidative status (TAS) were measured with spectrophotometric methods. According to the results, negative correlations of HDL (r = −0.593) and 25(OH)D (r = −0.340) and K (r = −0.220) were found, and positive expected correlations of LDL (r = 0.731), TC (r = 0.663), and TG (r = 0.584) with atheromatic index in the total studied sample were found. In conclusion, patients with a dyslipidemic profile should frequently check not only their lipid profile but also other biomarkers such as 25(OH)D, potassium, and oxidative stress markers to predict dyslipidemia and avoid subsequent disorders. Full article

(This article belongs to the Special Issue Journal of Xenobiotics: Feature Papers)

21 pages, 1838 KiB

Open AccessReview

Natural Products as a Tool to Modulate the Activity and Expression of Multidrug Resistance Proteins of Intestinal Barrier

by Carlos Martins-Gomes and Amélia M. Silva

J. Xenobiot. 2023, 13(2), 172-192; https://doi.org/10.3390/jox13020014 - 25 Mar 2023

Cited by 5 | Viewed by 2685

Abstract

The role of intestinal barrier homeostasis in an individual’s general well-being has been widely addressed by the scientific community. Colorectal cancer is among the illnesses that most affect this biological barrier. While chemotherapy is the first choice to treat this type of cancer, [...] Read more.

The role of intestinal barrier homeostasis in an individual’s general well-being has been widely addressed by the scientific community. Colorectal cancer is among the illnesses that most affect this biological barrier. While chemotherapy is the first choice to treat this type of cancer, multidrug resistance (MDR) is the major setback against the commonly used drugs, with the ATP-binding cassette transporters (ABC transporters) being the major players. The role of P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), or breast cancer resistance protein (ABCG2) in the efflux of chemotherapeutic drugs is well described in cancer cells, highlighting these proteins as interesting druggable targets to reverse MDR, decrease drug dosage, and consequently undesired toxicity. Natural products, especially phytochemicals, have a wide diversity of chemical structures, and some particular classes, such as phenolic acids, flavonoids, or pentacyclic triterpenoids, have been reported as inhibitors of P-gp, MRP1, and ABCG2, being able to sensitize cancer cells to chemotherapy drugs. Nevertheless, ABC transporters play a vital role in the cell’s defense against xenobiotics, and some phytochemicals have also been shown to induce the transporters’ activity. A balance must be obtained between xenobiotic efflux in non-tumor cells and bioaccumulation of chemotherapy drugs in cancer cells, in which ABC transporters are essential and natural products play a pivotal role that must be further analyzed. This review summarizes the knowledge concerning the nomenclature and function of ABC-transporters, emphasizing their role in the intestinal barrier cells. In addition, it also focuses on the role of natural products commonly found in food products, e.g., phytochemicals, as modulators of ABC-transporter activity and expression, which are promising nutraceutical molecules to formulate new drug combinations to overcome multidrug resistance. Full article

(This article belongs to the Special Issue Journal of Xenobiotics: Feature Papers)

► Show Figures

Figure 1

Journal Menu

Journal Browser

J. Xenobiot., Volume 13, Issue 2 (June 2023) – 8 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI