Remediation of benzo[α]pyrene contaminated soil using iron naturally bearing in tropical soil: A new frontier in catalyst-free in soil remediation.

Nature iron is considered one of the promising catalysts in advanced oxidation processes (AOPs) that are utilized for soil remediation from polycyclic aromatic hydrocarbons (PAHs). However, the existence of anions, cations, and organic matter in soils considered impurities that restricted the utilization of iron that was harnessed naturally in the soil matrix and reduced the catalytic performance. In this regard, tropical soil naturally containing iron and relatively poor with impurities was artificially contaminated with 100 mg/50 g benzo[α]pyrene (B[α]P) and remediated using a slurry phase reactor supported with persulfate (PS). The results indicated that tropical soil containing iron and relatively poor with impurities capable of activating the oxidants and formation of radicals which successfully degraded B[α]P. The optimum removal result was 86% and obtained under the following conditions airflow = 260 mL/min, temperature 55 , pH 7, and [PS]0 = 1.0 g/L, at the same experimental conditions soil organic matter (SOM) mineralization was 48%. After the remediation process, there was a significant reduction in iron and aluminum contents, which considered the drawbacks of this system. Experiments to scavenge reactive species highlighted and as the main radicals that oxidized B[α]P. Additionally, monitoring of by-products post-remediation aimed to assess toxicity and elucidate degradation pathways. Mutagenicity tests yielded positive results for two B[α]P by-products. The toxicity tests considered were the lethal concentration of 50% (LC50 96 h) for fat-head minnows revealed that all B[α]P by-products were less toxic than the parent pollutant itself. This research marks a significant advancement in soil remediation by advancing the use of the AOP method, removing the requirement for additional catalysts in the AOP system for the removal of B[α]P from soil.

Benzo(a)pyrene exposure during pregnancy leads to germ cell apoptosis in male mice offspring via affecting histone modifications and oxidative stress levels.

Infertility has gradually become a global health concern, and evidence suggests that exposure to environmental endocrine-disrupting chemicals (EDCs) represent one of the key causes of infertility. Benzo(a)pyrene (BaP) is a typical EDC that is widespread in the environment. Previous studies have detected BaP in human urine, semen, cervical mucus, oocytes and follicular fluid, resulting in reduced fertility and irreversible reproductive damage. However, the mechanisms underlying the effects of gestational BaP exposure on offspring fertility in male mice have not been fully explored. In this study, pregnant mice were administered BaP at doses of 0, 5, 10 and 20 mg/kg/day via gavage from Days 7.5 to 12.5 of gestation. The results revealed that BaP exposure during pregnancy disrupted the structural integrity of testicular tissue, causing a disorganized arrangement of spermatogenic cells, compromised sperm quality, elevated levels of histone modifications and increased apoptosis in the testicular tissue of F1 male mice. Furthermore, oxidative stress was also increased in the testicular tissue of F1 male mice. BaP activated the AhR/ERα signaling pathway, affected H3K4me3 expression and induced apoptosis in testicular tissue. AhR and Cyp1a1 were overexpressed, and the expression of key molecules in the antioxidant pathway, including Keap1 and Nrf2, was reduced. The combined effects of these molecules led to apoptosis in testicular tissues, damaging and compromising sperm quality. This impairment in testicular cells further contributed to compromised testicular tissues, ultimately impacting the reproductive health of F1 male mice.

Trajectories of long-term exposure to PCB153 and Benzo[a]pyrene (BaP) air pollution and risk of breast cancer.

BACKGROUND: While genetic, hormonal, and lifestyle factors partially elucidate the incidence of breast cancer, emerging research has underscored the potential contribution of air pollution. Polychlorinated biphenyls (PCBs) and benzo[a]pyrene (BaP) are of particular concern due to endocrine-disrupting properties and their carcinogenetic effect. OBJECTIVE: To identify distinct long term trajectories of exposure to PCB153 and BaP, and estimate their associations with breast cancer risk. METHODS: We used data from the XENAIR case-control study, nested within the ongoing prospective French E3N cohort which enrolled 98,995 women aged 40-65 years in 1990-1991. Cases were incident cases of primary invasive breast cancer diagnosed from cohort entry to 2011. Controls were randomly selected by incidence density sampling, and individually matched to cases on delay since cohort entry, and date, age, department of residence, and menopausal status at cohort entry. Annual mean outdoor PCB153 and BaP concentrations at residential addresses from 1990 to 2011 were estimated using the CHIMERE chemistry-transport model. Latent class mixed models were used to identify profiles of exposure trajectories from cohort entry to the index date, and conditional logistic regression to estimate their association with the odds of breast cancer. RESULTS: 5058 cases and 5059 controls contributed to the analysis. Five profiles of trajectories of PCB153 exposure were identified. The class with the highest PCB153 concentrations had a 69% increased odds of breast cancer compared to the class with the lowest concentrations (95% CI 1.08, 2.64), after adjustment for education and matching factors. The association between identified BaP trajectories and breast cancer was weaker and suffered from large CI. CONCLUSIONS: Our results support an association between long term exposure to PCB153 and the risk of breast cancer, and encourage further studies to account for lifetime exposure to persistent organic pollutants.

Recent trends and future perspectives of photoresponsive-based mercury (II) sensors and their biomaterial applications.

Recent advancements in the field of photoresponsive-based mercury (II) sensors have witnessed a surge in research focused on enhancing detection capabilities. Leveraging innovations in materials science, particularly with quantum dots, nanomaterials, and organic semiconductors, these sensors exhibit improved selectivity and sensitivity. Beyond traditional applications, such as environmental monitoring, the integration of photoresponsive principles with emerging technologies like the internet of things (IoT) and wearable promises real-time and remote mercury (II) ion detection. The on-going efforts also explore multifunctional sensors and miniaturization for on-site applications, addressing current challenges and paving the way for broader commercialization. This dynamic landscape underscores the potential for these sensors to play a crucial role in ensuring the effective monitoring and management of mercury (II) levels in diverse settings.

A Quantitative Adverse Outcome Pathway for Embryonic Activation of the Aryl Hydrocarbon Receptor of Fishes by Polycyclic Aromatic Hydrocarbons Leading to Decreased Fecundity at Adulthood.

Quantitative adverse outcome pathways (qAOPs) describe the response-response relationships that link the magnitude and/or duration of chemical interaction with a specific molecular target to the probability and/or severity of the resulting apical-level toxicity of regulatory relevance. The present study developed the first qAOP for latent toxicities showing that early life exposure adversely affects health at adulthood. Specifically, a qAOP for embryonic activation of the aryl hydrocarbon receptor 2 (AHR2) of fishes by polycyclic aromatic hydrocarbons (PAHs) leading to decreased fecundity of females at adulthood was developed by building on existing qAOPs for (1) activation of the AHR leading to early life mortality in birds and fishes, and (2) inhibition of cytochrome P450 aromatase activity leading to decreased fecundity in fishes. Using zebrafish (Danio rerio) as a model species and benzo[a]pyrene as a model PAH, three linked quantitative relationships were developed: (1) plasma estrogen in adult females as a function of embryonic exposure, (2) plasma vitellogenin in adult females as a function of plasma estrogen, and (3) fecundity of adult females as a function of plasma vitellogenin. A fourth quantitative relationship was developed for early life mortality as a function of sensitivity to activation of the AHR2 in a standardized in vitro AHR transactivation assay to integrate toxic equivalence calculations that would allow prediction of effects of exposure to untested PAHs. The accuracy of the predictions from the resulting qAOP were evaluated using experimental data from zebrafish exposed as embryos to another PAH, benzo[k]fluoranthene. The qAOP developed in the present study demonstrates the potential of the AOP framework in enabling consideration of latent toxicities in quantitative ecological risk assessments and regulatory decision-making. Environ Toxicol Chem 2024;00:1-12. © 2024 SETAC.

Aortic Injury Induced by Benzo(a)pyrene and Atherogenic Diet Increased Hepatic FGF21 Expression in C57BL/6J Mice.

Background: Benzo(a)pyrene (BaP), an environmental toxicant and endocrine disruptor, has been shown to exacerbate atherosclerosis when combined with a high-fat diet. Fibroblast Growth Factor-21 (FGF21), a novel hormone with anti-atherosclerotic properties, is associated with the presence of atherosclerosis and reduces plaque formation in experimental animals. Objectives: The present study aimed to investigate the chronic effect of BaP injection on hepatic FGF21 expression, as an anti-atherosclerotic hormone, in mice fed with or without an atherogenic diet (AtD). Methods: Eighteen C57BL/6J male mice (6 weeks) were randomly divided into six groups based on the dosage and diet. Blood samples were collected, and serum cholesterol, triglyceride, HDL-C, LDL-C, and glucose levels were measured. FGF21 expression was assessed by quantitative real-time PCR. Atherosclerotic lesions in mice were studied with Oil Red O (ORO) staining. Results: Benzo(a)pyrene causes a significant increase in liver FGF21 expression in a dose-dependent manner, and BaP co-exposure with AtD leads to a further increase in FGF21 expression. Additionally, the addition of BaP to AtD significantly increased the serum glucose, cholesterol, and LDL-C levels and accelerated the formation of atherosclerotic lesions. Besides, our findings showed that there is a significant positive correlation between FGF21 expression and glucose, cholesterol, LDL-C, and ORO-positive areas. Conclusions: Our findings revealed that BaP increases the expression of endogenous FGF21 in treated animals as a compensatory response to protect the heart from atherosclerosis induced by BaP and AtD.

Removal of benzo[a]pyrene from the soil by adsorption coupled with degradation on saponin-modified bentonite immobilized crude enzymes.

Bentonite is a non-metallic mineral with montmorillonite as the main component. It is an environmentally friendly mineral material with large reserves, wide distribution, and low price. Bentonite can be easily modified organically using the surfactant saponin to obtain saponin-modified bentonite (Sap-BT). This study investigates the immobilization of crude enzymes obtained from Trametes versicolor by physical adsorption with Sap-BT. Thus, saponin-modified bentonite immobilized crude enzymes (CE-Sap-BT) were developed to remove benzo[a]pyrene. Immobilization improves the stability of free enzymes. CE-Sap-BT can maintain more than 80% of activity at 45 °C and after storage for 15 d. Additionally, CE-Sap-BT exhibited a high removal rate of benzo[a]pyrene in soil, with 65.69% after 7 d in highly contaminated allotment soil and 52.90% after 6 d in actual soil contaminated with a low concentration of benzo[a]pyrene at a very low laccase dosage (0.1 U/3 g soil). The high catalytic and removal performance of CE-Sap-BT in contaminated sites showed more excellent practical application value.

Taxis-enhanced mineralization and co-metabolism of PAHs by bacteria in micrometer-scale environments.

Polycyclic aromatic hydrocarbons (PAHs) are associated with micropores in sediments and soils. This limits the bioaccessibility of these compounds via existing bioremediation technologies, as biodegradation is strongly influenced by the ability of bacteria to access different sizes of pores. In this work, we employed naphthalene and pyrene as model contaminants to evaluate the transformation capacity of the soil bacterium Pseudomonas putida G7 (2 × 1 µm) via mineralization and co-metabolic activity, respectively. Under non-growing conditions and in the absence of hydraulic flow, we examined how the tactic behavior of this motile bacterium influenced biodegradation of these two PAHs when passing through membranes with micrometer-sized pores (3 and 5 µm). The bacteria were spontaneously retained by the membranes, which blocked the contaminants away from a passive dosing source. However, the cells were mobilized through 5 µm pores after the application plant root exudate components (γ-aminobutyric acid, citrate and fructose) as strong chemoeffectors, which enhanced the mineralization of naphthalene and co-metabolism of pyrene. The tactic-mediated biodegradation enhancement did not occur through 3 µm pores, possibly due a physical constrain to the gradient sensing mechanism. Our results suggest that bacterial transport by chemotaxis may enhance the biotransformation of poorly bioaccessible contaminants present in micro-meter scale environments.

Metabolomic and biochemical disorders reveal the toxicity of environmental microplastics and benzo[a]pyrene in the marine polychaete Hediste diversicolor.

Recently, the abundance of environmental microplastics (MPs) has become a global paramount concern. Besides the danger of MPs for biota due to their tiny size, these minute particles may act as vectors of other pollutants. This study focused on evaluating the toxicity of environmentally relevant concentrations of MPs (10 and 50 mg/kg sediment) and benzo[a]pyrene (B[a]P, 1 µg/kg sediment), alone and in mixture, for 3 and 7 days in marine polychaete Hediste diversicolor, selected as a benthic bioindicator model. The exposure period was sufficient to confirm the bioaccumulation of both contaminants in seaworms, as well as the potential capacity of plastic particles to adsorb and vehiculate the B[a]P. Interestingly, increase of acidic mucus production was observed in seaworm tissues, indicative of a defense response. The activation of oxidative system pathways was demonstrated as a strategy to prevent lipid peroxidation. Furthermore, the comprehensive Nuclear Magnetic Resonance (NMR)-based metabolomics revealed significant disorders in amino acids metabolism, osmoregulatory process, energetic components, and oxidative stress related elements. Overall, these findings proved the possible synergic harmful effect of MPs and B[a]P even in small concentrations, which increases the concern about their long-term presence in marine ecosystems, and consequently their transfer and repercussions on marine fauna.

High Expression of AhR and Environmental Pollution as AhR-Linked Ligands Impact on Oncogenic Signaling Pathways in Western Patients with Gastric Cancer-A Pilot Study.

The vast majority of gastric cancer (GC) cases are adenocarcinomas including intestinal and diffuse GC. The incidence of diffuse GC, often associated with poor overall survival, has constantly increased in Western countries. Epidemiological studies have reported increased mortality from GC after occupational exposure to pro-carcinogens that are metabolically activated by cytochrome P450 enzymes through aryl hydrocarbon receptor (AhR). However, little is known about the role of AhR and environmental AhR ligands in diffuse GC as compared to intestinal GC in Western patients. In a cohort of 29, we demonstrated a significant increase in AhR protein and mRNA expression levels in GCs independently of their subtypes and clinical parameters. AhR and RHOA mRNA expression were correlated in diffuse GC. Further, our study aimed to characterize in GC how AhR and the AhR-related genes cytochrome P450 1A1 (CYP1A1) and P450 1B1 (CYP1B1) affect the mRNA expression of a panel of genes involved in cancer development and progression. In diffuse GC, CYP1A1 expression correlated with genes involved in IGF signaling, epithelial-mesenchymal transition (Vimentin), and migration (MMP2). Using the poorly differentiated KATO III epithelial cell line, two well-known AhR pollutant ligands, namely 2-3-7-8 tetrachlorodibenzo-p-dioxin (TCDD) and benzo[a]pyrene (BaP), strongly increased the expression of CYP1A1 and Interleukin1ß (IL1B), and to a lesser extend UGT1, NQO1, and AhR Repressor (AhRR). Moreover, the increased expression of CYP1B1 was seen in diffuse GC, and IHC staining indicated that CYP1B1 is mainly expressed in stromal cells. TCDD treatment increased CYP1B1 expression in KATO III cells, although at lower levels as compared to CYP1A1. In intestinal GC, CYP1B1 expression is inversely correlated with several cancer-related genes such as IDO1, a gene involved in the early steps of tryptophan metabolism that contributes to the endogenous AhR ligand kynurenine expression. Altogether, our data provide evidence for a major role of AhR in GC, as an environmental xenobiotic receptor, through different mechanisms and pathways in diffuse and intestinal GC. Our results support the continued efforts to clarify the identity of exogenous AhR ligands in diffuse GC in order to define new therapeutic strategies.

Percutaneous Absorption of Fireground Contaminants: Naphthalene, Phenanthrene, and Benzo[a]pyrene in Porcine Skin in an Artificial Sweat Vehicle.

Firefighters face significant risks of exposure to toxic chemicals, such as polycyclic aromatic hydrocarbons (PAHs), during fire suppression activities. PAHs have been found in the air, on the gear and equipment, and in biological samples such as the skin, breath, urine, and blood of firefighters after fire response. However, the extent to which exposure occurs via inhalation, dermal absorption, or ingestion is unclear. In this study, three PAHs, naphthalene, phenanthrene, and benzo[a]pyrene, were applied to porcine skin in vitro in an artificial sweat solution to better gauge firefighters' dermal exposures while mimicking their sweaty skin conditions using an artificial sweat dosing vehicle. Multiple absorption characteristics were calculated, including cumulative absorption, percent dose absorbed, diffusivity, flux, lag time, and permeability. The absorption of the PAHs was greatly influenced by their molecular weight and solubility in the artificial sweat solution. Naphthalene had the greatest dose absorption efficiency (35.0 ± 4.6% dose), followed by phenanthrene (6.8 ± 3.2% dose), and lastly, benzo[a]pyrene, which had the lowest absorption (0.03 ± 0.04% dose). The lag times followed a similar trend. All chemicals had a lag time of approximately 60 min or longer, suggesting that chemical concentrations on the skin may be reduced by immediate skin cleansing practices after fire exposure.

Meta-analysis identifies key genes and pathways implicated in Benzo[a]pyrene exposure response.

INTRODUCTION: Benzo[a]pyrene (B[a]P) is a carcinogenic polycyclic aromatic hydrocarbon that poses significant risks to human health. B[a]P influences cellular processes via intricate interactions; however, a comprehensive understanding of B[a]P's effects on the transcriptome remains elusive. This study aimed to conduct a comprehensive analysis focused on identifying relevant genes and signaling pathways affected by B[a]P exposure and their impact on human gene expression. METHODS: We searched the Gene Expression Omnibus database and identified four studies involving B[a]P exposure in human cells (T lymphocytes, hepatocellular carcinoma cells, and C3A cells). We utilized two approaches for differential expression analysis: the LIMMA package and linear regression. A meta-analysis was utilized to combine log fold changes (FC) and p-values from the identified studies using a random effects model. We identified significant genes at a Bonferroni-adjusted significance level of 0.05 and determined overlapping genes across datasets. Pathway enrichment analysis elucidated key cellular processes modulated by B[a]P exposure. RESULTS: The meta-analysis revealed significant upregulation of CYP1B1 (log FC = 1.15, 95% CI: 0.51-1.79, P < 0.05, I2 = 82%) and ASB2 (log FC = 0.44, 95% CI: 0.20-0.67, P < 0.05, I2 = 40%) in response to B[a]P exposure. Pathway analyses identified 26 significantly regulated pathways, with the top including Aryl Hydrocarbon Receptor Signaling (P = 0.00214) and Xenobiotic Metabolism Signaling (P = 0.00550). Key genes CYP1A1, CYP1B1, and CDKN1A were implicated in multiple pathways, highlighting their roles in xenobiotic metabolism, oxidative stress response, and cell cycle regulation. CONCLUSION: The results provided insights into the mechanisms of B[a]P toxicity, highlighting CYP1B1's key role in B[a]P bioactivation. The findings underscored the complexity of B[a]P's mechanisms of action and their potential implications for human health. The identified genes and pathways provided a foundation for further exploration and enhanced our understanding of the multifaceted biological activities associated with B[a]P exposure.

Integrated network toxicology, transcriptomics and gut microbiomics reveals hepatotoxicity mechanism induced by benzo[a]pyrene exposure in mice.

Benzo[a]pyrene (BaP) is a ubiquitous environmental pollutant posing various toxicity effects on organisms. Previous studies demonstrated that BaP could induce hepatotoxicity, while the underlying mechanism remains incompletely elucidated. In this study, a comprehensive strategy including network toxicology, transcriptomics and gut microbiomics was applied to investigate the hepatotoxicity and the associated mechanism of BaP exposure in mice. The results showed that BaP induced liver damage, liver oxidative stress and hepatic lipid metabolism disorder. Mechanistically, BaP may disrupt hepatic lipid metabolism through increasing the uptake of free fatty acid (FFA), promoting the synthesis of FA and triglyceride (TG) in the liver and suppressing lipid synthesis in white adipose tissue. Moreover, integrated network toxicology and hepatic transcriptomics revealed that BaP induced hepatotoxicity by acting on several core targets, such as signal transducer and activator of transcription 1 (STAT1), C-X-C motif chemokine ligand 10 (CXCL10) and toll-like receptor 2 (TLR2). Further analysis suggested that BaP inhibited JAK2-STAT3 signaling pathway, as supported by molecular docking and western blot. The 16S rRNA sequencing showed that BaP changed the composition of gut microbiota which may link to the hepatotoxicity based on the correlation analysis. Taken together, this study demonstrated that BaP caused liver injury, hepatic lipid metabolism disorder and gut microbiota dysbiosis, providing novel insights into the hepatotoxic mechanism induced by BaP exposure.

Benzopyrene represses mitochondrial fission factors and PINK1/Parkin-mediated mitophagy in primary astrocytes.

Mitochondria are essential for various physiological functions in astrocytes in the brain, such as maintaining ion and pH homeostasis, regulating neurotransmission, and modulating neuroinflammation. Mitophagy, a form of autophagy specific to mitochondria, is essential for ensuring mitochondrial quality and function. Benzo[a]pyrene (BaP) accumulates in the brain, and exposure to it is recognized as an environmental risk factor for neurodegenerative diseases. However, while the toxic mechanisms of BaP have been investigated in neurons, their effects on astrocytes-the most prevalent glial cells in the brain-are not clearly understood. Therefore, this study aims to investigate the toxic effects of exposure to BaP on mitochondria in primary astrocytes. Fluorescent probes and genetically encoded indicators were utilized to visualize mitochondrial morphology and physiology, and regulatory factors involved in mitochondrial morphology and mitophagy were assessed. Additionally, the mitochondrial respiration rate was measured in BaP-exposed astrocytes. BaP exposure resulted in mitochondrial enlargement owing to the suppression of mitochondrial fission factors. Furthermore, BaP-exposed astrocytes demonstrated reduced mitophagy and exhibited aberrant mitochondrial function and physiology, such as altered mitochondrial respiration rates, increased mitochondrial superoxide, disrupted mitochondrial membrane potential, and dysregulated mitochondrial Ca2+. These findings offer insights into the underlying toxic mechanisms of BaP exposure in neurodegenerative diseases by inducing aberrant mitophagy and mitochondrial dysfunction in astrocytes.

Flexibility of Poly(alkyl methacrylate)s Characterized by Their Persistence Length Determined through Pyrene Excimer Formation.

A series of poly(alkyl methacrylate)s and poly(oligo(ethylene glycol) methyl ether methacrylate)s labeled with 1-pyrenebutanol were referred to as the PyC4-PCnMA samples with n = 1, 4, 6, 8, 12, and 18 and the PyC4-PEGnMA samples with n = 0-5, 9, 16, and 19, respectively. Pyrene excimer formation (PEF) upon the encounter between an excited and a ground-state pyrenyl labels was employed to determine their persistence length (lp) in o-xylene. The fluorescence decays of the PyC4-PCnMA and PyC4-PEGnMA samples were acquired and analyzed with the fluorescence blob model to yield the number (Nblob) of structural units in the volume probed by an excited pyrenyl label. Nblob was found to decrease with an increasing number (NS) of non-hydrogen atoms in the side chain, reaching a plateau for the PyC4-PEGnMA samples with a longer side chain (n = 16 and 19). The Nblob values were used to determine lp. The lp values for the PyC4-PCnMA and PyC4-PEGnMA samples increased linearly with increasing NS2 as predicted theoretically, which agreed with the lp values obtained by viscometry for a series of PCnMA samples. The good agreement between the lp values retrieved by PEF and viscometry served to validate the PEF-based methodology for determining lp for linear polymers.

Lighting Up Bispyrene-Functionalized Chiral Molecular Muscles with Switchable Circularly Polarized Excimer Emissions.

Aiming at the further extension of the application scope of traditional molecular muscles, a novel bispyrene-functionalized chiral molecular [c2]daisy chain was designed and synthesized. Taking advantage of the unique dimeric interlocked structure of molecular [c2]daisy chain, the resultant chiral molecular muscle emits strong circularly polarized luminescence (CPL) attributed to the pyrene excimer with a high dissymmetry factor (glum) value of 0.010. More importantly, along with the solvent- or anion- induced motions of the chiral molecular muscle, the precise regulation of the pyrene stacking within its skeleton results in the switching towards either "inversed" state with sign inversion and larger glum values or "down" state with maintained handedness and smaller glum values, making it a novel multistate CPL switch. As the first example of chiral molecular muscle-based CPL switch, this proof-of-concept study not only successfully widens the application scopes of molecular muscles, but also provides a promising platform for the construction of novel smart chiral luminescent materials for practical applications.

Effects of in utero benzo[a]pyrene exposure on the testis of rats during puberty and the protective effect of atorvastatin.

Benzo[a]pyrene (BaP) is a contaminant that is generated in the environment through processes such as smoke, incomplete combustion of fossil fuels, vehicle exhaust emissions, entry into the body is through inhalation, and consumption of contaminated food. It is an omnipresent environmental pollutant with unavoidable exposure. BaP metabolites are observed in the male reproductive system, especially in the testes and epididymis of animals, and are responsible for reduced testicular and epididymal function. The protective effect of atorvastatin (ATV) on testicular damage was investigated previously. The aim of the present study was to investigate the protective effect of ATV on testicular toxicity induced by benzo[a]pyrene (BaP) during pregnancy in Wistar rats. This experimental laboratory study involved 40 adult rats, divided into seven groups and maintained under standard environmental conditions. The groups received different diets [control, corn oil, ATV (10 mg/kg), BaP (10 and 20 mg/kg), and ATV + BaP (10 and 20 mg/kg)] at gestation Days 7-16, orally. Male offspring were examined 10 weeks after birth. Testis and serum samples were collected, and testosterone level, malondialdehyde (MDA), and glutathione (GSH) were measured. Histological and immunohistochemical assays were performed under a light microscope. Statistical analysis was conducted using SPSS, with analysis of variance and Tukey tests to assess significant differences between groups. ATV significantly reduced MDA, a marker of lipid peroxidation and oxidative stress in rat testes following BaP administration. Treatment with ATV at doses of 10 mg/kg increased GSH levels, correcting disruptions in the antioxidant system caused by BaP. Testosterone concentration in rats treated with ATV and BaP substantially prevented the decrease induced by BaP. Histomorphometry revealed that ATV significantly prevented the detrimental effects of BaP on the thickness of spermatogenic epithelium and the diameter of seminiferous tubules. Under ATV treatment, testicular tissue histopathology improved, and spermatogenesis returned to a almost back to normal state. Caspase-3 expression decreased, and apoptosis activity in testicular tissue improved under ATV treatment, indicating a positive effect of ATV in reducing apoptotic damage caused by BaP. In conclusion, exposure to BaP can induce oxidative stress-related damage to testicular tissue, as evidenced by an increase in MDA levels, which ATV treatment can mitigate. Additionally, ATV enhances intracellular antioxidant GSH and protects the testes against BaP-induced damage while increasing testosterone levels, which are reduced due to exposure to BaP.

Effects of Benzo[α]pyrene on Mucus Secretion and Tissue Remodeling in a Rat Model of Allergic Rhinitis.

OBJECTIVES: Exposure to benzo[α]pyrene (BaP) increases the incidence and severity of allergic rhinitis (AR), but the underlying mechanisms remain unclear. Thus, we investigated the in vivo effects of BaP exposure on mucus hypersecretion and tissue remodeling in a rat model of AR. METHODS: Female Sprague-Dawley rats were randomly divided into 4 groups: a negative control group, a group of healthy rats exposed to BaP, a group of rats with ovalbumin (OVA)-induced AR, and a group of AR model rats exposed to BaP. Nasal symptoms and levels of OVA-specific serum immunoglobulin E (IgE) were measured in each individual rat. Moreover, examination of goblet cell hyperplasia and collagen deposition was carried out with periodic acid-Schiff (PAS) staining and Masson trichrome (MT) staining. Mucin 5AC (MUC5AC) expression was assessed by immunohistochemistry. RESULTS: BaP significantly increased the number of sneezes, the number of nasal rubs and the levels of OVA-specific serum IgE in rats with AR. Statistically significant differences in goblet cell hyperplasia and collagen deposition were observed between the BaP-exposed AR model group and the AR model group. Immunohistochemical results showed that the nasal mucosa of AR model rats displayed markedly elevated MUC5AC expression after BaP exposure. CONCLUSION: Our data indicate that mucus hypersecretion and the development of nasal remodeling might be pathophysiologic mechanisms underlying increased susceptibility to AR after exposure to BaP.

Structure Elucidation of Pharmaceutically Relevant Compounds within Pyrene-based Frameworks.

Single crystal X-ray diffraction (SCXRD) is the preferred and most accurate technique for determining molecular structures. However, it can present challenges when dealing with specific small molecules and active pharmaceutical ingredients (APIs), as many do not form quality crystals without coformers or can be unstable. In this study, we introduce tetrakis(guanidinium) pyrenetetrasulfonate (G4PYR), a robust guanidinium-organosulfonate (GS) framework that efficiently encapsulates small molecules and APIs rich in functional groups. The hydrogen bonding frameworks formed by G4PYR display well-ordered structures with predictable pyrene-pyrene distances, making them ideally suited for targeting arene-based APIs with pendant groups. Successful encapsulation of various guests, including benzaldehyde, benzamide, and arenes containing multiple hydrogen bond donors and acceptors like uracil and thymine, was achieved. Furthermore, we successfully encapsulated important pharmaceutical and biologically relevant compounds, such as lidocaine, ropinirole, adenosine, thymidine, and others. Notably, we present a workflow for investigating host-guest complex formation using powder X-ray diffraction and high throughput experimentation.

Impact of Skin Exposure to Benzo[a]pyrene in Rat Model: Insights into Epidermal Cell Function and Draining Lymph Node Cell Response.

The skin is a direct target of the air pollutant benzo[a]pyrene (BaP). While its carcinogenic qualities are well-studied, the immunotoxicity of BaP after dermal exposure is less understood. This study examines the immunomodulatory effects of a 10-day epicutaneous BaP application, in environmentally/occupationally relevant doses, by analyzing ex vivo skin immune response (skin explant, epidermal cells and draining lymph node/DLN cell activity), alongside the skin's reaction to sensitization with experimental hapten dinitrochlorobenzene (DNCB). The results show that BaP application disrupts the structure of the epidermal layer and promotes immune cell infiltration in the dermis. BaP exposure led to oxidative stress in epidermal cells, characterized by decreased reduced glutathione and increased AHR and Cyp1A1 expression. Production and gene expression of proinflammatory cytokines (TNF, IL-1ß) by epidermal cells decreased, while IL-10 response increased. Decreased spontaneous production of IFN-γ and IL-17, along with unchanged IL-10, was observed in DLC cells, whereas ConA-stimulated production of these cytokines was elevated. Local immunosuppression caused by BaP application seems to reduce the skin's response to an additional stimulus, evidenced by decreased effector activity of DLN cells three days after sensitization with DNCB. These findings provide new insight into the immunomodulatory effects and health risks associated with skin exposure to BaP.