Effect of topical bromfenac on intraretinal cystoid lesion in simultaneous cataract and idiopathic epiretinal membrane surgery.

PURPOSE: To investigate the effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs,) bromfenac on the intraretinal cystic lesions (IRC) when performing simultaneous cataract and idiopathic epiretinal membrane (iERM) surgery. METHODS: This study included patients with iERM who had been followed up for 6 months after vitrectomy, membrane removal, and concurrent cataract surgery. Eyes were treated with topical bromfenac or not. The baseline fluorescein angiography (FA) was obtained to assess the microvascular leakage (ML). Structural changes of macula, including IRC and central macular thickness (CMT) were assessed using optical coherence tomography (OCT). The main outcome measures were changes in IRCs and best-corrected visual acuity (BCVA) regarding FA findings. RESULTS: One hundred eighteen eyes were included. IRC and ML were observed in 51 eyes (43.2%) and 63 eyes (53.4%), respectively. The IRC did not show any association with the ML. Of total, 29 eyes (24.6%) were treated with topical bromfenac (Group A). Compared to Group B, topical bromfenac did not show beneficial effects in aspect of preventions for the newly developed IRC and treatment for pre-existed IRC. Whether the ML existed or not, topical bromfenac did not show any different effect on the changes in BCVA and IRC. CONCLUSION: When performing simultaneous cataract and ERM surgery, topical NSAIDs, bromfenac did not show beneficial effects on the preventions and treatment of IRC in both eyes with and without the ML.

Role of microsomal metabolism in bromfenac-induced cytotoxicity.

This study delves into the intricate mechanisms underlying drug-induced liver injury (DILI) with a specific focus on bromfenac, the withdrawn nonsteroidal anti-inflammatory drug. DILI is a pervasive concern in drug development, prompting market withdrawals and posing significant challenges to healthcare. Despite the withdrawal of bromfenac due to DILI, the exact role of its microsomal metabolism in inducing hepatotoxicity remains unclear. Herein, employing HepG2 cells with human liver microsomes and UDP-glucuronic acid (UDPGA), our investigation revealed a substantial increase in bromfenac-induced cytotoxicity in the presence of UDPGA, pointing to the significance of UDP-glucuronosyltransferase (UGT)-dependent metabolism in augmenting toxicity. Notably, among the recombinant UGTs examined, UGT2B7 emerged as a pivotal enzyme in the metabolic activation of bromfenac. Metabolite identification studies disclosed the formation of reactive intermediates, with bromfenac indolinone (lactam) identified as a potential mediator of hepatotoxic effects. Moreover, in cytotoxicity experiments, the toxicity of bromfenac lactam exhibited a 34-fold increase, relative to bromfenac. The toxicity of bromfenac lactam was mitigated by nicotinamide adenine dinucleotide phosphate-dependent metabolism. This finding underscores the role of UGT-dependent metabolism in generating reactive metabolites that contribute to the observed hepatotoxicity associated with bromfenac. Understanding these metabolic pathways and the involvement of specific enzymes, such as UGT2B7, provides crucial insights into the mechanisms of bromfenac-induced liver injury. In conclusion, this research sheds light on the metabolic intricacies leading to cytotoxicity induced by bromfenac, especially emphasizing the role of UGT-dependent metabolism and the formation of reactive intermediates like bromfenac lactam. These findings offer insight into the mechanistic basis of DILI and emphasize the importance of understanding metabolism-mediated toxicity.

Transcriptome-based approach to identify mechanisms underlying locomotor abnormality induced by decabromodiphenyl ethane in zebrafish larvae.

The brominated flame retardant decabromodiphenyl ethane (DBDPE) has been extensively used following restrictions on BDE-209 and thus, been frequently detected in aquatic environment. However, information on impact of DBDPE on fish development and the potential mechanisms remains scarce. In present study, developing zebrafish were employed as a study model. Embryos were exposed until 5 d to DBDPE at concentrations of 0, 3, 30, and 300 µg/L, following which the impact on larval development was investigated. DBDPE bioaccumulation and locomotor hyperactivity were observed in developing zebrafish exposed to DBDPE. Transcriptome and bioinformatics analyses indicated that pathways associated with cardiac muscle contraction and retinol metabolism were notably affected. The mechanisms of DBDPE to induce locomotor abnormality were further investigated by analyzing levels of retinol and retinol metabolites, eye and heart histology, heart rates, and ATPase activity. Our results indicate that locomotor hyperactivity observed in larvae exposed to DBDPE results from abnormal heartbeat, which in turn is attributable to inhibition of Na+/K+-ATPase activity. Furthermore, DBDPE did not change larval eye histology and contents of retinoid (retinol, retinal, and retinoic acid). This study provides insight into the mechanisms underlying DBDPE-induced developmental toxicity and highlights the need for addressing the environmental risks for aquatic organisms.

Evidence for Adverse Effects on Liver Development and Regeneration in Zebrafish by Decabromodiphenyl Ethane.

Decabromodiphenyl ethane (DBDPE), a ubiquitous emerging pollutant, could be enriched in the liver of organisms, but its effects and mechanisms on liver development and regeneration remain largely unknown. In the present study, we first investigated the adverse effects on liver development and found decreased area and intensity of fluorescence in transgenic zebrafish larvae exposed to DBDPE; further results in wild-type zebrafish larvae revealed a possible mechanism involving disturbed MAPK/Fox O signaling pathways and cell cycle arrest as indicated by decreased transcription of growth arrest and DNA-damage-inducible beta a (gadd45ba). Subsequently, an obstructed recovery process of liver tissue after partial hepatectomy was characterized by the changing profiles of ventral lobe-to-intestine ratio in transgenic female adults upon DBDPE exposure; further results confirmed the adverse effects on liver regeneration by the alterations of the hepatic somatic index and proliferating cell nuclear antigen expression in wild-type female adults and also pointed out a potential role of a disturbed signaling pathway involving cell cycles and glycerolipid metabolism. Our results not only provided novel evidence for the hepatotoxicity and underlying mechanism of DBDPE but also were indicative of subsequent ecological and health risk assessment.

Hydroxylated transformation products obtained after UV irradiation of the current-use brominated flame retardants hexabromobenzene, pentabromotoluene, and pentabromoethylbenzene.

Hexabromobenzene (HBB), pentabromotoluene (PBT), and pentabromoethylbenzene (PBEB) are current-use brominated flame retardants (cuBFRs) which have been repeatedly detected in environmental samples. Since information on hydroxylated transformation products (OH-TPs) was scarcely available, the three polybrominated compounds were UV irradiated for 10 min in benzotrifluoride. Fractionation on silica gel enabled the separate collection and identification of OH-TPs. For more insights, aliquots of the separated OH-TPs were UV irradiated for another 50 min (60 min total UV irradiation time). The present investigation of polar UV irradiation products of HBB, PBT, and PBEB was successful in each case. Altogether, eight bromophenols were detected in the case of HBB (three Br3-, four Br4-, and one Br5-isomer), and nine OH-TPs were observed in the case of PBT/PBEB (six Br3- and three Br4-congeners). In either case, Br➔OH exchange was more relevant than H➔OH exchange. Also, such exchange was most relevant in meta- and ortho-positions. As a further point, and in agreement with other studies, the transformation rate decreased with decreasing degree of bromination. UV irradiation of HBB additionally resulted in the formation of tri- and tetrabrominated dihydroxylated compounds (brominated diphenols) that were subsequently identified. These dihydroxylated transformation products were found to be more stable than OH-TPs.

Evaluation and Mechanistic Study of Transgenerational Neurotoxicity in Zebrafish upon Life Cycle Exposure to Decabromodiphenyl Ethane (DBDPE).

The novel brominated flame retardant decabromodiphenyl ethane (DBDPE) has become a ubiquitous emerging pollutant in the environment, which may evoke imperceptible effects in humans or wild animals. Hence in this study, zebrafish embryos were exposed to DBDPE (0, 0.1, 1, and 10 nM) until sexual maturity (F0), and F1 and F2 generations were cultured without further exposure to study the multi- and transgenerational toxicity and underlying mechanism. The growth showed sex-different changing profiles across three generations, and the social behavior confirmed transgenerational neurotoxicity in adult zebrafish upon life cycle exposure to DBDPE. Furthermore, maternal transfer of DBDPE was not detected, whereas parental transfer of neurotransmitters to zygotes was specifically disturbed in F1 and F2 offspring. A lack of changes in the F1 generation and opposite changing trends in the F0 and F2 generations were observed in a series of indicators for DNA damage, DNA methylation, and gene transcription. Taken together, life cycle exposure to DBDPE at environmentally relevant concentrations could induce transgenerational neurotoxicity in zebrafish. Our findings also highlighted potential impacts on wild gregarious fish, which would face higher risks from predators.

Toxicity of decabromodiphenyl ethane on lettuce: Evaluation through growth, oxidative defense, microstructure, and metabolism.

Decabromodiphenyl ethane (DBDPE) as the most widely used novel brominated flame retardants (NBFRs), has become a ubiquitous emerging pollutant in the environment. However, its toxic effects on vegetable growth during agricultural production have not been reported. In this study, we investigated the response mechanisms of hydroponic lettuce to DBDPE accumulation, antioxidant stress, cell structure damage, and metabolic pathways after exposure to DBDPE. The concentration of DBDPE in the root of lettuce was significantly higher than that in the aboveground part. DBDPE induced oxidative stress on lettuce, which stimulated the defense of the antioxidative system of lettuce cells, and the cell structure produced slight plasma-wall separation. In terms of metabolism, metabolic pathway disorders were caused, which are mainly manifested as inhibiting amino acid biosynthesis and metabolism-related pathways, interfering with the biosyntheses of amino acids, organic acids, fatty acids, carbohydrates, and other substances, and ultimately manifested as decreased total chlorophyll content and root activity. In turn, metabolic regulation alleviated antioxidant stress. The mechanisms of the antioxidative reaction of lettuce to DBDPE were elucidated by IBR, PLS-PM analysis, and molecular docking. Our results provide a theoretical basis and research necessity for the evaluation of emerging pollutants in agricultural production and the safety of vegetables.

Mitochondrial Dysfunction Was Involved in Decabromodiphenyl Ethane-Induced Glucolipid Metabolism Disorders and Neurotoxicity in Zebrafish Larvae.

Decabromodiphenyl ethane (DBDPE), a novel brominated flame retardant, is becoming increasingly prevalent in environmental and biota samples. While DBDPE has been shown to cause various biological adverse effects, the molecular mechanism behind these effects is still unclear. In this research, zebrafish embryos were exposed to DBDPE (50-400 µg/L) until 120 h post fertilization (hpf). The results confirmed the neurotoxicity by increased average swimming speed, interfered neurotransmitter contents, and transcription of neurodevelopment-related genes in zebrafish larvae. Metabolomics analysis revealed changes of metabolites primarily involved in glycolipid metabolism, oxidative phosphorylation, and oxidative stress, which were validated through the alterations of multiple biomarkers at various levels. We further evaluated the mitochondrial performance upon DBDPE exposure and found inhibited mitochondrial oxidative respiration accompanied by decreased mitochondrial respiratory chain complex activities, mitochondrial membrane potential, and ATP contents. However, addition of nicotinamide riboside could effectively restore DBDPE-induced mitochondrial impairments and resultant neurotoxicity, oxidative stress as well as glycolipid metabolism in zebrafish larvae. Taken together, our data suggest that mitochondrial dysfunction was involved in DBDPE-induced toxicity, providing novel insight into the toxic mechanisms of DBDPE as well as other emerging pollutants.

Involvement of Bmal1 and Clock in Bromobenzene Metabolite-Induced Diurnal Renal Toxicity.

Circadian rhythms are endogenous oscillators that regulate 24 h behavioral and physiological processes. Our previous investigation demonstrated that bromobenzene metabolite (4-bromocatechol: 4-BrCA) exhibited chronotoxicity (i.e., the nephrotoxicity induced by 4-BrCA was observed during the dark phase, while not observed at light phase in mice). However, the molecular mechanism is still unknown. The aim of the present study is to investigate the cellular molecule(s) involved in the 4-BrCA-induced nephrotoxicity using mouse renal cortex tubular cell lines (MuRTE61 cells). We found that 4-BrCA showed dose dependent (0.01-1 mM) cell proliferation defect in MuRTE61 cells. By treating with 0.03 mM 4-BrCA, we demonstrated that major clock genes (Bmal1, Clock, Cry1, Cry2, Per1, and Per2) were significantly downregulated. Interestingly, the expression levels of two genes, Bmal1 and Clock, continued to decrease after 3 h of treatment with 4-BrCA, while Cry1, Per1, and Per2 were unchanged until 24 h of treatment. Moreover, BMAL1 and CLOCK levels are higher at light phase. We speculated that BMAL1 and CLOCK might function defensively against 4-BrCA-induced nephrotoxicity since the expression levels of Bmal1 and Clock were rapidly decreased. Finally, overexpression of Bmal1 and Clock restored 4-BrCA-induced cell proliferation defect in MuRTE61 cells. Taken together, our results suggest that Bmal1 and Clock have protective roles against 4-BrCA-induced nephrotoxicity.

Influence of organic cosolvents on hexabromobenzene degradation in solution by montmorillonite-templated subnanoscale zero-valent iron.

Organic cosolvents are commonly used to increase the dissolution of poorly water-soluble organic pollutants into aqueous solutions during environmental remediation. In this study, the influences of five organic cosolvents on hexabromobenzene (HBB) degradation catalyzed by one typical reactive material montmorillonite-templated subnanoscale zero-valent iron (CZVI) were investigated. The results demonstrated that all cosolvents promoted HBB degradation but the degree of promotion was different for different cosolvents, which was associated with inconsistent solvent viscosities, dielectric constant properties, and the extent of interactions between cosolvents with CZVI. Meanwhile, HBB degradation was highly dependent on the volume ratio of cosolvent to water, which increased in the range of 10%-25% but persistently decreased in the range of more than 25%. This might be due to the fact that the cosolvents increased HBB dissolution at low concentrations but reduced the protons supplied by water and the contact between HBB with CZVI at high concentrations. In addition, the freshly-prepared CZVI had higher reactivity to HBB than the freeze-dried CZVI in all water-cosolvent solutions, probably because freeze-drying reduced the interlayer space of CZVI and thus the contact probability between HBB and active reaction sites. Finally, the CZVI-catalyzed HBB degradation mechanism was proposed as the electron transfer between zero-valent iron and HBB, which led to the formation of four debromination products. Overall, this study provides helpful information for the practical application of CZVI in the remediation of persistent organic pollutants in the environment.

Emission and environmental distribution of decabromodiphenyl ethane (DBDPE) in China from 2006 to 2026: Retrospection, forecasting, and implications for assessment and management.

Decabromodiphenyl ethane (DBDPE) is the main alternative to decabromodiphenyl ether (deca-BDE) in commercial use. However, there is increasing evidence show that DBDPE is a potential persistent organic pollutant, and it has been found ubiquitously in environmental media across China in recent years. Monitoring studies have not been able to determine the overall levels and temporal trends of DBDPE contamination in China, and have been unable to explain how emission patterns can affect their environmental distribution. Therefore, this study estimated the temporal variance of DBDPE emissions and environmental concentrations in five regions of China from 2006 to 2026 using the PROduction-To-EXposure (PROTEX) mass balance model. The results showed that Guangdong Province was the greatest DBDPE pollution hotspot in China due to emissions from plastics manufacturing and e-waste disposal; there was also severe pollution in Shandong Province, where almost all the DBDPE in China is produced. The DBDPE concentrations in indoor and outdoor environments increased substantially in all regions during 2006-2021. Furthermore, in Guangdong Province and Shandong Province, the ratio of indoor/outdoor air concentrations was greater than or close to 1, indicative of significant outdoor emission sources of DBDPE. In contrast, the ratios for the Beijing-Tianjin-Hebei region, East China, and Southwest China were below 1 due to the indoor use of electronic equipment containing DBDPE. The temporal trends of these ratios indicated that DBDPE contamination has gradually spread from high-concentration environments with strong emission sources to low-concentration environments. The outcomes of this study have important implications for the risk assessment of DBDPE use in China and can be used to establish contamination-mitigation actions.

Investigating the adverse outcome pathways (AOP) of neurotoxicity induced by DBDPE with a combination of in vitro and in silico approaches.

Current studies have shown an association between DBDPE and neurotoxicity. In this study, the adverse outcome pathway (AOP) and mechanistic analysis of DBDPE-induced neurotoxicity were explored by a combination of in vitro and in silico approaches in SK-N-SH cells. DBDPE-induced oxidative stress caused DNA strand breaks, resulting in the activation of poly (ADP-ribose) (PAR) polymerase-1 (PARP-1). Activation of PARP1 could cause toxic damage in various organ systems, especially in the nervous system. DBDPE-induced apoptosis via the caspase-dependent intrinsic mitochondrial pathway and the PARP1-dependent pathway. Activation of PARP1 by DBDPE was deemed the initiating event, thereby affecting the key downstream biochemical events (e.g., ROS production, DNA damage, membrane potential changes, and ATP reduction), which induced apoptosis. Furthermore, excessive activation of PARP1 was accompanied by the translocation of the apoptosis-inducing factor (AIF), which was associated with PARP1-dependent cell death. The inhibition of PARP1 by PJ34 reduced DBDPE-induced apoptosis and maintained cellular ATP levels. PJ34 also prevented the translocation of AIF from the mitochondria to the nucleus. These findings improve the understanding of the mechanism of DBDPE-induced neurotoxic effects and provide a theoretical basis for the ecological risk of DBDPE.

Multi- and Transgenerational Developmental Impairments Are Induced by Decabromodiphenyl Ethane (DBDPE) in Zebrafish Larvae.

A novel brominated flame retardant decabromodiphenyl ethane (DBDPE) has become a ubiquitous emerging pollutant; hence, the knowledge of its long-term toxic effects and underlying mechanism would be critical for further health risk assessment. In the present study, the multi- and transgenerational toxicity of DBDPE was investigated in zebrafish upon a life cycle exposure at environmentally relevant concentrations. The significantly increased malformation rate and declined survival rate specifically occurred in unexposed F2 larvae suggested transgenerational development toxicity by DBDPE. The changing profiles revealed by transcriptome and DNA methylome confirmed an increased susceptibility in F2 larvae and figured out potential disruptions of glycolipid metabolism, mitochondrial energy metabolism, and neurodevelopment. The changes of biochemical indicators such as ATP production confirmed a disturbance in the energy metabolism, whereas the alterations of neurotransmitter contents and light-dark stimulated behavior provided further evidence for multi- and transgenerational neurotoxicity in zebrafish. Our findings also highlighted the necessity for considering the long-term impacts when evaluating the health of wild animals as well as human beings by emerging pollutants.

Optimization of hyaluronan-enriched cubosomes for bromfenac delivery enhancing corneal permeation: characterization, ex vivo, and in vivo evaluation.

To design and evaluate hyaluronan-based cubosomes loaded with bromfenac sodium (BS) for ocular application to enhance the corneal permeation and retention in pterygium and cataract treatment. BS-loaded cubosomes were prepared by the emulsification method, employing 23 full factorial design using Design-Expert® software. Glycerol monoolein (GMO) and poloxamer 407 (P407) as lipid phase and polyvinyl alcohol (PVA) as stabilizer were the used ingredients. The optimized formulation (OBC; containing GMO (7% w/w), P407 (0.7% w/w) and PVA (2.5% w/w)) was further evaluated. OBC had an entrapment efficiency of 61.66 ± 1.01%, a zeta potential of -30.80 ± 0.61 mV, a mean particle size of 149.30 ± 15.24 nm and a polydispersity index of 0.21 ± 0.02. Transmission electron microscopy confirmed its cubic shape and excellent dispersibility. OBC exhibited high stability and no ocular irritation that was ensured by histopathology. Ex vivo permeation study showed a significant increase in drug deposition and permeability parameters through goat cornea, besides, confocal laser microscopy established the superior permeation capability of OBC, as compared to drug solution. In vivo pharmacokinetics in aqueous humor indicated higher AUC0-tlast (18.88 µg.h/mL) and mean residence time (3.16 h) of OBC when compared to the marketed eye drops (7.93 µg.h/mL and 1.97 h, respectively). Accordingly, hyaluronan-enriched cubosomes can be regarded as a promising carrier for safe and effective topical ocular delivery.

Is it really safe to replace decabromodiphenyl ether (BDE209) with decabromodiphenyl ethane (DBDPE)?: A perspective from hepatotoxicity.

In this paper, the hepatocytotoxicity and aryl hydrocarbon receptor (AHR) activity of decabromodiphenyl ethane (DBDPE), decabromodiphenyl ether (BDE209) and other 18 analogues were evaluated in vitro using human normal liver cell L02. These dioxin-like compounds showed differential hepatocytotoxicity (EC50  = 0.38-17.87 mg/L) and AHR activity (EROD activity = 4.53-46.35 U/µg). In silico study indicated the distance of π-π bonds between the benzene ring of compounds and residue Phe234 of AHR played a key role in the binding of AHR, and the substituents on the benzene ring also influenced the activity. Combining molecular biology and bioomics, the comprehensive investigations on the hepatotoxic mechanisms have demonstrated the AHR signaling pathway was the key mediation mechanism for the hepatotoxicity of DBDPE/BDE209. The cytochrome P450s (CYP2 family) mediated formation of reactive oxygenated intermediates might be the dominant toxic mechanism, which could produce oxidative stress or cause genotoxicity. Although the experimental toxicity of DBDPE was smaller relative to BDE209, the health risk of DBDPE may be much greater than we expected, due to the high potential to form a variety of dioxin-like intermediates by microbial oxidation of ethyl group. Therefore, whether it is really safe to replace BDE209 with DBDPE is a debatable question, and more ecotoxicological and health data are needed to clarify this issue.

Histopathological and transcriptomic analyses reveal the reproductive endocrine-disrupting effects of decabromodiphenyl ethane (DBDPE) in mussel Mytilus galloprovincialis.

The novel brominated flame retardant DBDPE has become a widespread environmental contaminant and could affect reproductive endocrine system in vertebrates. However, information about reproductive endocrine-disrupting effects of DBDPE on invertebrates is totally unknown. In this study, mussels Mytilus galloprovincialis were exposed to 1, 10, 50, 200 and 500 µg/L DBDPE for 30 days. Histopathological and transcriptomic analyses were performed to assess the reproductive endocrine-disrupting effects of DBDPE in mussels and the potential mechanisms. DBDPE promoted the gametogenesis in mussels of both sexes according to histological observation, gender-specific gene expression (VERL and VCL) and histological morphometric parameter analysis. Transcriptomic analysis demonstrated that DBDPE suppressed the genes related to cholesterol homeostasis and transport in both sexes via different LRPs- and ABCs-mediated pathways. DBDPE also disturbed nongenomic signaling pathway including signaling cascades (GPR157-IP3-Ca2+) in males and secondary messengers (cGMP) in females, and subsequently altered the expression levels of reproductive genes (VMO1, ZAN, Banf1 and Hook1). Additionally, dysregulation of energy metabolism in male mussels induced by DBDPE might interfere with the reproductive endocrine system. Overall, this is the first report that DBDPE evoked reproductive endocrine-disruptions in marine mussels. These findings will provide important references for ecological risk assessment of DBDPE pollution in marine environment.

Rational Design, Synthesis, and Anti-Proliferative Evaluation of Novel 4-Aryl-3,4-Dihydro-2H-1,4-Benzoxazines.

A synthetic pathway to a novel 4-aryl-3,4-dihydro-2H-1,4-benzoxazine scaffold was developed and a series of compounds based on the scaffold were synthesised as potential anticancer agents. The 4-aryl-substituted compounds were prepared via Buchwald-Hartwig cross-coupling between substituted bromobenzenes and various 1,4-benzoxazines, which in turn were generated from a cascade hydrogenation and reductive amination one-pot reaction. These analogues exhibited moderate to good potency against various cancer cell lines. Structure-activity relationship analysis indicated that the inclusion of hydroxyl groups on ring A and ring B was beneficial to biological activity, while having a para-amino group on ring C significantly enhanced potency. Molecule 14f displayed the most potent anticancer activity (IC50 = 7.84-16.2 µM against PC-3, NHDF, MDA-MB-231, MIA PaCa-2, and U-87 MG cancer cell lines), indicating its potential as a lead compound for further structural optimisation. All the synthesised compounds were fully characterised with NMR, HMRS, and IR. The novel benzoxazine scaffold described in this study holds promise and deserves further in-depth studies.

Effects and mechanisms of decabromodiphenyl ethane on Chlorella sorokiniana: Transcriptomics, proteins and fatty acid production.

Decabromodiphenyl ethane is a novel brominated flame retardant, that has always been dissolved in organic solvents to explore its activities on aquatic organisms. In this study, the influences of decabromodiphenyl ethane on the microalga Chlorella sorokiniana (C. sorokiniana) were studied, and three microalgae treatments, including decabromodiphenyl ethane dissolved in dimethyl sulfoxide solvent (DBDPE treatment), dimethyl sulfoxide alone (control II) or untreated (control I) were used in the experiment, respectively. The results showed that the growth of C. sorokiniana was remarkably enhanced in the DBDPE treatment compared with the control I and II groups. Conjoint analysis of transcriptomics and quantitative proteome displayed that the upregulated differentially expressed genes and proteins of DBDPE:control I were enriched in 6 pathways, and downregulated genes/proteins of DBDPE:control I were enriched in 3 pathways. The upregulated differentially expressed genes and proteins of DBDPE:control II were enriched in 4 pathways, and downregulated genes/proteins of DBDPE:control II were enriched in 6 pathways. In addition, decabromodiphenyl ethane changed the fatty acid concentration in C. sorokiniana cells. The activities of superoxide dismutase were enhanced when C. sorokiniana were treated by decabromodiphenyl ethane. The data highlighted that the mRNA and protein expression relating to the fatty acid production, of C. sorokiniana were significantly affected by decabromodiphenyl ethane, and decabromodiphenyl ethane pollution changed the physiological metabolism of microalgae and had harmful effects on natural environments.

Decabromodiphenyl ethane induces male reproductive toxicity by glycolipid metabolism imbalance and meiotic failure.

Decabromodiphenyl ethane (DBDPE) is a typical flame retardant found in various electrical and textile items. DBDPE is abundantly available in the surrounding environment and wild animals based on its persistence and bioaccumulation. DBDPE has been shown to cause apoptosis in rat spermatogenic cells, resulting in reproductive toxicity. However, the toxicity of DBDPE on the male reproductive system and the potential mechanisms are still unclear. This study evaluated the effect of DBDPE on the reproductive system in male SD rats and demonstrated the potential mechanisms of reproductive toxicity. DBDPE (0, 5, 50, and 500 mg/kg/day) was administered via gavage to male SD rats for 28 days. DBDPE caused histopathological changes in the testis, reduced sperm quantity and motility, and raised the malformation rate in rats, according to the findings. Furthermore, it caused DNA damage to rat testicular cells. It inhibited the expressions of spermatogenesis-and oogenesis-specific helix-loop-helix transcription factor 1 (Sohlh1), piwi-like RNA-mediated gene silencing 2 (MILI), cyclin-dependent kinase 2 (CDK2), and CyclinA, resulting in meiotic failure, as well as the expressions of synaptonemal complex proteins 1 and 3 (SYCP1 and SYCP3), leading to chromosomal association disorder in meiosis and spermatocyte cycle arrest. Moreover, DBDPE induced glycolipid metabolism disorder and activated mitochondria-mediated apoptosis pathways in the testes of SD rats. The quantity and quality of sperm might be declining due to these factors. Our findings offer further evidence of the harmful impact of DBDPE on the male reproductive system.

Integration of transcriptomic and proteomic reveals the toxicological molecular mechanisms of decabromodiphenyl ethane (DBDPE) on Pleurotus ostreatus.

Decabromodiphenyl ethane (DBDPE), as one of the most widely used new brominated flame retardants (NBFRs), can pose a potential threat to human health and the environment. An integrated transcriptome and proteome was performed for investigating the toxicological molecular mechanisms of Pleurotus ostreatus (P. ostreatus) during the biodegradation of DBDPE at the concentrations of 5 and 20 mg/L. A total of 1193/1018 and 92/126 differentially expressed genes/proteins (DEGs/DEPs) were found, respectively, with DBDPE exposure at 5 and 20 mg/L. These DEGs and DEPs were mainly involved in the cellular process as well as metabolic process. DEPs for oxidation-reduction process and hydrolase activity were up-regulated, and those for membrane, lipid metabolic process and transmembrane transport were down-regulated. The DEGs and DEPs related to some key enzymes were down-regulated, such as NADH dehydrogenase/oxidoreductase, succinate dehydrogenase, cytochrome C1 protein, cytochrome-c oxidase/reductase and ATP synthase, which indicated that DBDPE affected the oxidative phosphorylation as well as tricarboxylic acid (TCA) cycle. Cytochrome P450 enzymes (CYPs) might be involved in DBDPE degradation through hydroxylation and oxidation. Some stress proteins were induced to resist DBDPE toxicity, including major facilitator superfamily (MFS) transporter, superoxide dismutase (SOD), molecular chaperones, heat shock proteins (HSP20, HSP26, HSP42), 60S ribosomal protein and histone H4. The findings help revealing the toxicological molecular mechanisms of DBDPE on P. ostreatus, aiming to improve the removal of DBDPE.