Xenobiotic Agents Research Articles

An Updated Review on the Role of Phytoconstituents in Modulating Signalling Pathways to Combat Skin Ageing: Nature’s Own Weapons and Approaches

Abstract: Various geographical areas exhibit varying degrees of prevalence and severity of dermatological issues. The most commonly observed skin issues among adolescents during their growth period on a global scale encompass dry skin, dyspigmentation, wrinkles, fungal infections, as well as benign and malignant tumors. These conditions arise as a consequence of diminished functional capacity and heightened skin susceptibility. The primary manifestation of the whole process of skin ageing is its visual presentation, which encompasses changes in both the structure and function of the skin. The look and function of human skin exhibit particular variations as individuals age, representing a time-dependent phenomenon. This review article primarily examines the discussion surrounding the diverse phytoconstituents and their impact on signalling pathways in cellular metabolism, as well as their interaction with environmental factors and xenobiotic agents that contribute to skin aging. Ultraviolet (UV) light induces the rapid formation and subsequent accumulation of reactive oxygen species (ROS) within skin cells, hence accelerating oxidative stress and the ageing process of the skin. One effective approach to addressing age-related skin disorders entails the utilization of exogenous supplementation through the consumption of dietary antioxidants, as well as the application of antioxidant-based lotions to the skin prior to sun exposure. Several plant species include phenolic components, including ascorbic acid, ellagitannins, and carotenoids, which have the ability to protect the skin from harmful UV radiation, reduce inflammation and oxidative stress, and influence several survival signalling pathways. This comprehensive study elucidated multiple processes by which phytoconstituents exert their effects for intervention purposes. Additionally, it highlighted the ability of these phytoconstituents to modulate the NF-κB signalling pathway, MAPK signalling, Nrf2 signalling, and other pathways, hence demonstrating their potential anti-aging properties.

The use of the micronucleus test and comet assay in wild rodents: a historical review and future perspectives.

Rodents are considered good models for investigating genotoxic damage and mutagenic alterations caused by xenobiotic agents, due to their occupation of a wide variety of habitats. However, relatively few in situ studies have focused on DNA damage in wild rodents associated with environmental exposure. In this review, we investigate trends in the application of the micronucleus test and comet assay in in situ studies of wild rodents. A total of 33 papers were identified, distributed across 14 different countries. Brazil and Spain had the most published studies (six each), followed by Bulgaria (n = 5), Mexico (n = 4) and Italy (n = 3). Only 24 of the 2,652 recognized rodent species have been the subject of in situ studies, which have most frequently focus on species of the genus Mus. The protocols used for the micronucleus test and comet assay varied widely, although blood and bone marrow were the primary types of tissue used. Given the paucity of studies on wild rodents, we recommend further research, particularly focusing on the use of this group as bioindicators of environmental quality and the standardization of protocols.

Endoplasmic reticulum transporter OAT2 regulates drug metabolism and interaction

Xenobiotic metabolic reactions in the hepatocyte endoplasmic reticulum (ER) including UDP-glucuronosyltransferase and carboxylesterase play central roles in the detoxification of medical agents with small- and medium-sized molecules. Although the catalytic sites of these enzymes exist inside of ER, the molecular mechanism for membrane permeation in the ER remains enigmatic. Here, we investigated that organic anion transporter 2 (OAT2) regulates the detoxification reactions of xenobiotic agents including anti-cancer capecitabine and antiviral zidovudine, via the permeation process across the ER membrane in the liver. Pharmacokinetic studies in patients with colorectal cancer revealed that the half-lives of capecitabine in rs2270860 (1324C > T) variants was 1.4 times higher than that in the C/C variants. Moreover, the hydrolysis of capecitabine to 5′-deoxy-5-fluorocytidine in primary cultured human hepatocytes was reduced by OAT2 inhibitor ketoprofen, whereas capecitabine hydrolysis directly assessed in human liver microsomes were not affected. The immunostaining of OAT2 was merged with ER marker calnexin in human liver periportal zone. These results suggested that OAT2 is involved in distribution of capecitabine into ER. Furthermore, we clarified that OAT2 plays an essential role in drug-drug interactions between zidovudine and valproic acid, leading to the alteration in zidovudine exposure to the body. Our findings contribute to mechanistically understanding medical agent detoxification, shedding light on the ER membrane permeation process as xenobiotic metabolic machinery to improve chemical changes in hydrophilic compounds.

Toll-Like Receptors and Contact Dermatitis.

Contact dermatitis (CD) is a common cutaneous inflammatory condition that affects millions of people worldwide. Xenobiotic agents are frequently encountered in substances used in everyday life, making it difficult to avoid personal and occupational exposure. Toll-like receptors (TLRs) are transmembrane receptors that modulate the innate immune system in response to tissue injury or infection. TLRs play a key role in the pathophysiology of contact dermatitis. TLR signaling is involved in three major forms of CD: protein CD, allergic contact dermatitis (ACD), and irritant CD. Of the 10 TLRs found in humans, three play an important role in ACD. This makes TLRs a useful potential therapeutic target to consider against CD. In this review, we discuss the role of TLRs in CD and summarize current and emerging treatments for CD that target TLRs.

Exceptionally High Perfluorooctanoic Acid Uptake in Water by a Zirconium-Based Metal-Organic Framework through Synergistic Chemical and Physical Adsorption.

Perfluorooctanoic acid (PFOA) is an environmental contaminant ubiquitous in water resources, which as a xenobiotic and carcinogenic agent, severely endangers human health. The development of techniques for its efficient removal is therefore highly sought after. Herein, we demonstrate an unprecedented zirconium-based MOF (PCN-999) possessing Zr6 and biformate-bridged (Zr6)2 clusters simultaneously, which exhibits an exceptional PFOA uptake of 1089 mg/g (2.63 mmol/g), representing a ca. 50% increase over the previous record for MOFs. Single-crystal X-ray diffraction studies and computational analysis revealed that the (Zr6)2 clusters offer additional open coordination sites for hosting PFOA. The coordinated PFOAs further enhance the interaction between coordinated and free PFOAs for physical adsorption, boosting the adsorption capacity to an unparalleled high standard. Our findings represent a major step forward in the fundamental understanding of the MOF-based PFOA removal mechanism, paving the way toward the rational design of next-generation adsorbents for per- and polyfluoroalkyl substance (PFAS) removal.

Exosomes released by environmental pollutant-stimulated Keratinocytes/PBMCs can trigger psoriatic inflammation in recipient cells via the AhR signaling pathway.

Introduction: Exosomes, pivotal in intercellular communication during skin disease pathogenesis, have garnered substantial attention. However, the impact of environmental pollutants, such as benzo[a]pyrene (BaP) and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), on exosome release amid inflammatory skin diseases remains unexplored. This study addresses this gap by examining the influence of BaP and TCDD on exosome function, specifically focusing on immune-related pathway alterations in normal recipient keratinocytes and peripheral blood mononuclear cells (PBMCs). Methods: HaCaT cells were treated with exosomes from BaP- or TCDD-treated keratinocytes. Proinflammatory cytokines and chemokines, including TNF-α, IL-1β, IL-6, IL-8, CXCL1, and CXCL5, were assessed. The involvement of the p65NF-κB/p38MAPK/ERK signaling pathway in recipient keratinocytes was investigated. Aryl hydrocarbon receptor (AhR) silencing was employed to elucidate its role in mediating the proinflammatory response induced by exosomes from BaP- or TCDD-treated keratinocytes. Results and discussion: Treatment with exosomes from BaP- or TCDD-treated keratinocytes induced a significant increase in proinflammatory cytokines and chemokines in HaCaT cells. The upregulation implicated the p65NF-κB/p38MAPK/ERK signaling pathway. AhR silencing attenuated this response, suggesting a role for AhR in mediating this response. In PBMCs from healthy controls, exosomes from BaP-stimulated PBMCs of psoriatic patients led to increased expression of proinflammatory cytokines and modulation of Th1/Th17 cell distribution via AhR activation. These findings unveil a novel dimension in the interplay between environmental xenobiotic agents (BaP and TCDD) and exosomal functions. The study establishes their influence on psoriatic inflammatory responses, shedding light on the underlying mechanisms mediated through the AhR signaling pathway in recipient keratinocytes and PBMCs.

New insights in animal models of neurotoxicity-induced neurodegeneration.

The high prevalence of neurodegenerative diseases is an unintended consequence of the high longevity of the population, together with the lack of effective preventive and therapeutic options. There is great pressure on preclinical research, and both old and new models of neurodegenerative diseases are required to increase the pipeline of new drugs for clinical testing. We review here the main models of neurotoxicity-based animal models leading to central neurodegeneration. Our main focus was on studying how changes in neurotransmission and neuroinflammation, mainly in rodent models, contribute to harmful processes linked to neurodegeneration. The majority of the models currently in use mimic Parkinson's disease (PD) and Alzheimer's disease (AD), which are the most common neurodegenerative conditions in older adults. AD is the most common age-related dementia, whereas PD is the most common movement disorder with also cases of dementia. Several natural toxins and xenobiotic agents induce dopaminergic neurodegeneration and can reproduce neuropathological traits of PD. The literature analysis of MPTP, 6-OH-dopamine, and rotenone models suggested the latter as a useful model when specific doses of rotenone were administrated systemically to C57BL/6 mice. Cholinergic neurodegeneration is mainly modelled with the toxin scopolamine, which is a useful rodent model for the screening of protective drugs against cognitive decline and AD. Several agents have been used to model neuroinflammation-based neurodegeneration and dementia in AD, including lipopolysaccharide (LPS), streptozotocin, and monomeric C-reactive protein. The bacterial agent LPS makes a useful rodent model for testing anti-inflammatory therapies to halt the development and severity of AD. However, neurotoxin models might be more useful than genetic models for drug discovery in PD but that is not the case in AD where they cannot beat the new developments in transgenic mouse models. Overall, we should work using all available models, either in vivo, in vitro, or in silico, considering the seriousness of the moment and urgency of developing effective drugs.

Abstract 4424: Immunoregulatory role of club cell secretory proteins in non-small cell lung cancer

Abstract Introduction. Immune checkpoint inhibitors (ICI) particularly those targeting the PD-1/PD-L1 axis are approved for NSCLC patients. However, most patients experience little clinical benefit due to immunosuppressive barriers in the tumor microenvironment. Our goal to identify immunomodulatory agents that may overcome these barriers, led to the finding that low dose stereotactic body radiation therapy (SBRT) in combination with ICI resulted in marked tumor regression and improved survival by generating durable anti-tumor immunity (Ban et al., Nature Cancer, 2021). Unexpectedly, we uncovered that the immune-modulating functions of SBRT was acutely dependent on the secretory function of lung resident Scgb1a1+ club cells that protect the bronchioles from xenobiotic agents. Blocking club cell secretome in vivo blunted the efficacy of the combination treatment and altered myeloid cell phenotypes. These findings led to the hypothesis that radiation-induced club cell factors may synergize with ICI to attenuate immunosuppressive barriers by reducing myeloid suppressive cells. Methods and Data. Expression of 8 highest expressed club cells secretory factors (CC10, SP-A, SP-B, SP-D, Hp, Secretoglobin 3A1, 3A 2, and 1C 1) in combination with PD-1 blockade elicited significant tumor control and improved survival of NSCLC mice. Mechanistically, the 8 club cell factors inhibit myeloid suppressor cell phenotypes as determined by reduced pSTAT3, pERK and concomitant inhibition of immunosuppressive mediators Arg1, iNOS, etc. Further screening of individual club cell factors showed that CC10 alone effectively blunted myeloid suppression activity as determined by flow cytometry for Arg1 and iNOS. Hence, CC10 can functionally alter the immunosuppressive nature of myeloid suppressor cells. The ability of CC10 in improving the efficacy of ICI in impairing tumor growth and improving survival is currently being examined. Conclusions. Myeloid suppressor cells inhibit immune cells like T cells or NK cells leading to poor prognosis in cancer treatment. Increase in their numbers has been linked to tumor aggressiveness and low efficacy of immunotherapy. Hence, there is an unmet clinical need to specifically target these cells. Agents targeting myeloid suppressor cell accumulation and differentiation (e.g., ATRA, Vitamin D, Sunitinib, Gemcitabine, Bevacizumab, Tadalafil), are being tested in human clinical trials. However, these agents lack specificity and selectivity for myeloid suppressor cells in vivo. Therefore, our work provides the rationale for the development of CC10 as selective inhibitor of myeloid suppressor cells and has the potential for achieving a robust and durable anti-tumor immunity in NSCLC. Citation Format: Aakanksha Rajiv Kapoor, Vivek Mittal. Immunoregulatory role of club cell secretory proteins in non-small cell lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4424.

Innovative Strategies to Overcome Antimicrobial Resistance and Tolerance.

Antimicrobial resistance and tolerance are natural phenomena that arose due to evolutionary adaptation of microorganisms against various xenobiotic agents. These adaptation mechanisms make the current treatment options challenging as it is increasingly difficult to treat a broad range of infections, associated biofilm formation, intracellular and host adapted microbes, as well as persister cells and microbes in protected niches. Therefore, novel strategies are needed to identify the most promising drug targets to overcome the existing hurdles in the treatment of infectious diseases. Furthermore, discovery of novel drug candidates is also much needed, as few novel antimicrobial drugs have been introduced in the last two decades. In this review, we focus on the strategies that may help in the development of innovative small molecules which can interfere with microbial resistance mechanisms. We also highlight the recent advances in optimization of growth media which mimic host conditions and genome scale molecular analyses of microbial response against antimicrobial agents. Furthermore, we discuss the identification of antibiofilm molecules and their mechanisms of action in the light of the distinct physiology and metabolism of biofilm cells. This review thus provides the most recent advances in host mimicking growth media for effective drug discovery and development of antimicrobial and antibiofilm agents.

Hepatoprotective effect of a Novel Functional Drink based on Ecuadorian Plant Species

Liver diseases are considered a severe public health problem involving disorders that alter liver function. Since the liver plays an essential role in the metabolism and detoxification of substances that enter the organism, it is susceptible to damage caused by xenobiotic agents such as viruses, alcohol, and drugs. Acetaminophen is an over‐the‐counter drug widely used as an antipyretic and analgesic. It is safe at therapeutic doses, but it is easily overused, causing severe liver diseases. In a previous study, our investigation group developed a functional drink from the aqueous extracts of Ilex guayusa, Vernonanthura patens, and cocoa husks. This combination presented various bioactive compounds with antioxidant properties that could help reduce oxidative stress in pathologic conditions. For the above mentioned, the study's objective was to evaluate the hepatoprotective effect of the beverage through an in vivo test. Male mice were treated with two formulations (pre‐formulated and microencapsulated) of the functional drink in three concentrations for seven days as a preventive oral treatment. After that, mice were induced to liver damage at a single intraperitoneal dose of acetaminophen (250 mg/kg of body weight). The evaluation was based on the liver damage biomarkers, ALT, and AST; anatomopathological studies were also evaluated. The results showed that the best formulation as an oral pre‐treatment was the pre‐formulated. The pre‐formulated beverage attenuated the injury caused by the acetaminophen by inhibiting serum ALT and AST activities and reducing liver macro and microscopic liver alterations. The successful doses were at 250 and 1000 mg/kg b.w. The microencapsulated did not present adequate liver protection at any doses evaluated because it has no statistical difference with the toxic model group.In conclusion, the present study demonstrated for the first time that the functional drink effectively prevented acetaminophen‐induced liver injury in vivo. Our data indicated that the pre‐formulated was the most effective pre‐treatment to attenuate the hepatic injury. These results suggested that this beverage possessed antioxidative activity that likely contributed to its protective effect against acetaminophen liver damage.*Corresponding Author: Orellana‐Manzano Andrea, email: akorella@espol.edu.ec

Klebsiella oxytoca: an efficient pyrene-degrading bacterial strain isolated from petroleum-contaminated soil.

Polycyclic aromatic hydrocarbons (PAHs) are the hazardous xenobiotic agents of oil production. One of the methods to eliminate hazardous compounds is bioremediation, which is the most efficient and cost-effective method to eliminate the harmful byproducts of crude petroleum processing. In this study, five pure bacterial isolates were isolated from petroleum-contaminated soil, four of which showed a robust growth on the PAH pyrene, as a sole carbon source. Various methods viz mass spectroscopy, biochemical assays, and 16S RNA sequencing employed to identify the isolates ascertained the consistent identification of Klebsiella oxytoca by all three methods. Scanning electron microscopy and Gram staining further demonstrated the characterization of the K. oxytoca. High-performance liquid chromatography of the culture supernatant of K. oxytoca grown in pyrene containing media showed that the cells started utilizing pyrene from the 6th day onwards and by the 12th day of growth, 70% of the pyrene was completely degraded. A genome search for the genes predicted to be involved in pyrene degradation using Kyoto Encyclopedia of Genes and Genomes (KEGG) confirmed their presence in the genome of K. oxytoca. These results suggest that K. oxytoca would be a suitable candidate for removing soil aromatic hydrocarbons.

Responses of Escherichia coli and Listeria monocytogenes to ozone treatment on non-host tomato: Efficacy of intervention and evidence of induced acclimation.

Because of the continuous rise of foodborne illnesses caused by the consumption of raw fruits and vegetables, effective post-harvest anti-microbial strategies are necessary. The aim of this study was to evaluate the anti-microbial efficacy of ozone (O3) against two common causes of fresh produce contamination, the Gram-negative Escherichia coli O157:H7 and Gram-positive Listeria monocytogenes, and to relate its effects to potential mechanisms of xenobiosis by transcriptional network modeling. The study on non-host tomato environment correlated the dose × time aspects of xenobiosis by examining the correlation between bacterial survival in terms of log-reduction and defense responses at the level of gene expression. In E. coli, low (1 μg O3/g of fruit) and moderate (2 μg O3/g of fruit) doses caused insignificant reduction in survival, while high dose (3 μg/g of fruit) caused significant reduction in survival in a time-dependent manner. In L. monocytogenes, moderate dose caused significant reduction even with short-duration exposure. Distinct responses to O3 xenobiosis between E. coli and L. monocytogenes are likely related to differences in membrane and cytoplasmic structure and components. Transcriptome profiling by RNA-Seq showed that primary defenses in E. coli were attenuated after exposure to a low dose, while the responses at moderate dose were characterized by massive upregulation of pathogenesis and stress-related genes, which implied the activation of defense responses. More genes were downregulated during the first hour at high dose, with a large number of such genes getting significantly upregulated after 2 hr and 3 hr. This trend suggests that prolonged exposure led to potential adaptation. In contrast, massive downregulation of genes was observed in L. monocytogenes regardless of dose and exposure duration, implying a mechanism of defense distinct from that of E. coli. The nature of bacterial responses revealed by this study should guide the selection of xenobiotic agents for eliminating bacterial contamination on fresh produce without overlooking the potential risks of adaptation.

MiR-27b-3p a Negative Regulator of DSB-DNA Repair.

Understanding the regulation of DNA repair mechanisms is of utmost importance to identify altered cellular processes that lead to diseases such as cancer through genomic instability. In this sense, miRNAs have shown a crucial role. Specifically, miR-27b-3 biogenesis has been shown to be induced in response to DNA damage, suggesting that this microRNA has a role in DNA repair. In this work, we show that the overexpression of miR-27b-3p reduces the ability of cells to repair DNA lesions, mainly double-stranded breaks (DSB), and causes the deregulation of genes involved in homologous recombination repair (HRR), base excision repair (BER), and the cell cycle. DNA damage was induced in BALB/c-3T3 cells, which overexpress miR-27b-3p, using xenobiotic agents with specific mechanisms of action that challenge different repair mechanisms to determine their reparative capacity. In addition, we evaluated the expression of 84 DNA damage signaling and repair genes and performed pathway enrichment analysis to identify altered cellular processes. Taken together, our results indicate that miR-27b-3p acts as a negative regulator of DNA repair when overexpressed.

Antioral cancer effect of fucoxanthin on 7,12-dimethylbenz[a] anthracene-induced experimental cancer model hamster through changes of apoptosis and cell proliferation

Background: In this study, we investigated the chemopreventive efficacy of fucoxanthin (Fx) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral cancer in hamsters. Materials and Methods: Twenty-four male Syrian golden hamsters were randomly allotted to four groups with six hamsters each. Squamous cell carcinogenesis was initiated by administering 0.5% DMBA in the left oral mucosa of hamsters for 10 weeks. The complete formation of oral tumor (OT) was confirmed via hematoxylin and eosin staining and biochemical analysis, as well as via molecular markers using plasma samples and in buccal and liver tissue samples. Results: Significant increase in the level of antioxidant, lipid peroxides (LPOs), and liver marker enzymes was observed in control animals. Increased rate of cell proliferation and decreased expression of apoptotic proteins were observed in buccal tumor in control animals. Treatment of DMBA-induced animals with Fx (50 mg/kg body weight) resulted in mild-to-moderate premalignant lesions, such as hyperplasia and dysplasia, but control animals showed the development of OT. Furthermore, the levels of LPO, antioxidants, and xenobiotic agents were altered due to Fx-administered DMBA-induced hamster showed reduced expression pattern of proliferating cell nuclear antigen and moderate expression pattern of caspases-9 and 3 and p53 were observations. Conclusion: In this study, the chemoprotective potential of Fx was due to the antiproliferative, antiapoptotic, and antioxidant effects of Fx, as well as due to anti-LPO effects in the DMBA-induced hamster cheek pouch carcinogenesis.

Toxicokinetics an essential tool in drug discovery: A review article

Toxicokinetics is defined as the generation of pharmacokinetic data, as the passage through the body of a toxic agent or its metabolites, Toxicokinetics is the study of systemic exposure during toxicological experiments. The objective is to quantify the systemic exposure and potentially relate that to toxicology finding. Keywords: Pharmacokinetics, Toxic Injury, Toxicodynamics, Pesticide, Xenobiotic Agent, Biological Marker, Toxicity.

Characterization of cytochrome P450s (CYP)-overexpressing HepG2 cells for assessing drug and chemical-induced liver toxicity

Hepatic metabolism catalyzed by the cytochrome P450 (CYP) superfamily affects liver toxicity associated with exposures to natural compounds and xenobiotic agents. Previously we generated a battery of HepG2-derived stable cell lines that individually express 14 CYPs (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, and 3A7). In this study, we comprehensively characterized each cell line for its CYP expression and enzyme activity. Specifically, we measured the mRNA expression, protein expression, and metabolite formation. Using CYP3A4, 2D6, and 2C9-overexpressing cells as representatives, we examined the stability of these cells in long-term cultures for up to 10 passages. The results showed that CYPs can be stably overexpressed for up to 10 cell culture passages without losing their activities. The robustness of responses to stimuli among the cells at different passages was also investigated in CYP3A4-overexpressing cells and the response to amiodarone and dronedarone showed no difference between the cells at the passage 2 and 10. Moreover, the mRNA expression level of most CYPs was higher in CYP-overexpressing HepG2 cells than that in HepaRG cells and primary human hepatocytes. This study confirmed the stability of CYP-overexpressing HepG2 cell lines and provided useful information for a broader use of these cells in pharmacologic and toxicologic research.

Lead exposure affects cephalic morphogenesis and neural crest cells in Gallus gallus embryo

The morphogenesis of the head of vertebrates is a process that involves rapid growth and dynamic movements of various cell populations, including the neural crest cells (NCC). These pluripotent cells generated during neurulation have high proliferative and migratory capacity but xenobiotic agents can affect these migratory periods and cause congenital malformations. Lead (Pb) is the most common toxic metal in the environment and a potent teratogen that can affect growth and induce malformations. Despite the known toxic effects of Pb, there is a gap in knowledge about the impact of realistic concentrations of Pb at critical periods of early development. Here, we evaluated mortality, embryonic morphology, NCC migration, and the amount of Pb deposition in chicken embryos after 3 to 4 days of exposure. One of the most interesting observations in this study is that only about 34% of the injected Pb was present in the embryos after 4 days. We observed that exposure to Pb, even under low concentrations, increased mortality and the occurrence of malformations during embryonic development, especially in the cephalic region (CR). Although Pb was found widely distributed in the CR, no relation between its presence and the migration routes of cephalic NCC was observed. But the number of NCC and their migratory distance were reduced. These changes are consistent and explain the morphological anomalies described in this study, which also correlates with the morphofunctional abnormalities reported in the literature. Therefore, this study highlights the concern of exposure to low concentrations of this metal.

Etiologies of Liver Cytolysis in the Service of Hepato-Gastroenterology of the Gabriel Toure University Hospital

Aggression to the liver by xenobiotic and endogenous agents essentially results in an increase in serum aminotransferases related to hepatic cytolysis, the diagnosis of which is not always easy due to the diversity of its causes. This was a cross-sectional study from April 2019 to March 2020 that took place in the Department of Hepato-gastroenterology of the Gabriel Touré University Hospital Center. This was a cross-sectional study from April 2019 to March 2020 which took place in the Hepato Gastroenterology department of the Gabriel Touré university hospital whose objective of which was to study the etiology of hepatic cytolysis. We included all patients with hepatic cytolysis resulting in increased aminotransferase alanine at a rate higher than the normal upper limit with or without an increase of aspartate aminotransferase. We collected 199/2800 patients who met our inclusion criteria, i.e., a frequency of 7.1%. The mean age was 44.06 years ± 16.4 years, the sex ratio was 1.73. The most common clinical signs were jaundice, ascites, hepatomegaly, asthenia and anorexia. Biologically, chronic cytolysis was noted with a moderate elevation of aminotransferase alanine in 77.9% and a significant elevation in 15.5% of cases. HBs antigen (HBsAg) was positive in 80 patients (40.2%) and anti-hepatitis C virus (HCV) antibody in 18 patients (9%). Abdominal ultrasound was the first-line morphological examination and hepatomegaly alone or associated with splenomegaly was the most common abnormality. The main causes of acute cytolysis were viral hepatitis B, bile duct obstructions, drug-induced hepatitis and malaria while chronic cytolysis was mainly due to cirrhosis and hepatocellular carcinoma (HCC).

Soybean Plant Metabolism under Water Deficit and Xenobiotic and Antioxidant Agent Application.

The aim was to evaluate the interactive effects on biochemistry and physiology of soybean plants exposed to simultaneous xenobiotic and water deficit stresses, and the possible attenuation of plant damage by an antioxidant agent. Soybean plants were submitted to eight different soil water potentials, in two experiments (first experiment: −0.96, −0.38, −0.07, −0.02 MPa, and second experiment: −3.09, −1.38, −0.69, −0.14 MPa), xenobiotic, and antioxidant agent applications. Was observed a reduction in water status, gas exchange, photosynthetic pigments, photosystem II quantum yield, and increased leaf temperature in plants under low water availability. Water deficit also induced oxidative stress by the increased production of reactive oxygen species, cellular and molecular damage, and induction of the antioxidant defense metabolism, reduction of gas exchange, water status, and photosynthetic efficiency. The xenobiotic application also caused changes, with deleterious effects more pronounced in low soil water availability, mainly the reactive oxygen species production, consequently the antioxidant activity, and the oxidative damages. This indicates different responses to the combination of stresses. Antioxidant enzyme activity was reduced by the application of the antioxidant agent. Principal Component Analysis showed a relation with the antioxidant agent and reactive oxygen species, which is probably due to signaling function, and with defense antioxidant system, mainly glutathione, represented by thiols.

Endocrine Disruption and Reproductive Pathology.

During the past 20 years, investigations involving endocrine active substances (EAS) and reproductive toxicity have dominated the landscape of ecotoxicological research. This has occurred in concert with heightened awareness in the scientific community, general public, and governmental entities of the potential consequences of chemical perturbation in humans and wildlife. The exponential growth of experimentation in this field is fueled by our expanding knowledge into the complex nature of endocrine systems and the intricacy of their interactions with xenobiotic agents. Complicating factors include the ever-increasing number of novel receptors and alternate mechanistic pathways that have come to light, effects of chemical mixtures in the environment versus those of single EAS laboratory exposures, the challenge of differentiating endocrine disruption from direct cytotoxicity, and the potential for transgenerational effects. Although initially concerned with EAS effects chiefly in the thyroid glands and reproductive organs, it is now recognized that anthropomorphic substances may also adversely affect the nervous and immune systems via hormonal mechanisms and play substantial roles in metabolic diseases, such as type 2 diabetes and obesity.