Triphenyltin (TPT), a widespread organotin pollutant with significant ecological risks, has been reported to induce vascular injury, though the underlying mechanisms remain unclear. We hypothesized that TPT exposure impairs vascular development in zebrafish larvae through mitochondrial dysfunction and oxidative stress, leading to endothelial cell death and vascular structural defects. Here, we used transgenic zebrafish, imaging, histology, mitochondrial assays, qPCR and transcriptomics to assess TPT-induced vascular toxicity across morphological, functional and molecular levels. In this study, zebrafish larvae were exposed to TPT from 24 to 96 h post-fertilization at 12.5, 25, and 50 nM, corresponding to approximately 1/5, 1/3 and 3/4 of the 96-h LC50 (68 nM). The lowest concentration is within environmentally relevant ranges. TPT exposure caused pronounced vascular damage, as visualized using transgenic live imaging lines. At 50 nM TPT, heart rate decreased by 32%, blood flow velocity decreased by 58%, and intersegmental vessel length decreased by 45% (all p < 0.01 vs. control). At the cellular level, increased endothelial cell death was evident. Mechanistically, TPT exposure led to mitochondrial dysfunction, as indicated by reductions in mitochondrial content, and upregulated expression of pro-apoptotic genes such as bax and caspase-3. Contrary to our initial hypothesis, several VEGF/Notch signaling components (e.g., vegfaa, notch1) were significantly upregulated, which may represent a compensatory response rather than direct pathway suppression. All experiments included at least three biological replicates. Statistical significance was assessed by one-way ANOVA with Tukey's post-hoc test (p < 0.05). Collectively, these findings demonstrated that TPT exposure induces vascular developmental toxicity in zebrafish associated with mitochondrial dysfunction and cell death, along with dysregulated expression of VEGF/Notch pathway transcripts, and underscore the importance of further research on the ecological and health risks of organotin pollutants.

Triphenyltin (TPT) is a highly toxic organotin fungicide, widely found in all environments. Previous studies have demonstrated that TPT exposure causes hepatotoxicity and alters lipid profiles in livers and sera, however, the underlying mechanism between TPT-induced dysregulation of lipid metabolism and liver injury remains unclear, prompting us to investigate how TPT disturb lipid metabolic pathways to drive hepatic toxicity. This study used a multi-omics approach to investigate molecular responses associated with TPT-induced liver injury in zebrafish larvae. Zebrafish larvae were exposed to 15, 30 and 60 nmol/L TPT for 72 h. Transgenic zebrafish lines Tg (fabp10a: DsRed) and Tg (lyz: DsRed) were used to observe changes in liver area and inflammatory responses. The structural integrity of the liver was examined using HE staining and transmission electron microscope, while the presence of lipids in the zebrafish was assessed using Oil Red O, Nile Red and Sudan Black B staining. Transcriptomic and metabolomic analyses were conducted using whole-larvae samples to identify molecular pathways associated with the observed liver injury. The results indicate that TPT exposure causes liver inflammation and lipid accumulation. Differentially expressed genes and metabolites were primarily enriched in pathways related to PPAR signaling pathway, fatty acid metabolism and inflammation. RT-qPCR validation showed that changes in the expression of genes related to lipid metabolism were consistent with the omics results. In summary, TPT can cause liver injury in zebrafish by disrupting lipid metabolism and inflammation pathways. This study provides a theoretical basis for elucidating the mechanisms of TPT hepatotoxicity and for assessing the environmental risks of organotin compounds.

Objective: To investigate the potential mechanisms by which hexafluoropropylene oxide trimer acid (HFPO-TA), an emerging environmental contaminant, may induce retinal disease. An additional aim was to systematically examine the molecular pathways through which HFPO-TA may elicit retinal toxicity. Methods: Potential HFPO-TA targets related to retinal injury were predicted using PubChem, ADMETlab 3.0, and GeneCards, followed by PPI network construction with STRING and hub target screening using Cytoscape. GO and KEGG enrichment analyses were performed via DAVID, and molecular docking between HFPO-TA and selected targets was conducted using AutoDock Vina. For validation, zebrafish embryos were exposed to 80 mg/L HFPO-TA from 0 to 72 hpf. Retinal morphology was examined by H&E staining, and retinal injury-, inflammation-, and photoreceptor-related gene expression was assessed by RT-qPCR. Results: Network toxicology and molecular docking suggested that HFPO-TA may target retinal injury-related pathways, including lipid metabolism, adipokine signaling, apoptosis, inflammation, and potential carcinogenic processes. H&E staining demonstrated retinal structural abnormalities in HFPO-TA-exposed zebrafish larvae, including disorganized cell arrangement, enlarged intercellular spaces, and apparent OPL thinning. RT-qPCR further confirmed transcriptional alterations in genes related to retinal injury, inflammation, tissue remodeling, and photoreceptor function. Conclusion: In summary, the present study has revealed, for the first time, that HFPO-TA exerts a toxic effect on the retina. The study also provides forward-looking insights into the molecular mechanisms underlying HFPO-TA exposure-induced retinal diseases, and it lays foundations for several new research directions.

Hepatic triacylglycerol (TAG) metabolic dysregulation, characterized by concurrent enhancement of synthesis and attenuation of degradation, is fundamental to the pathogenesis of fatty liver in dairy cows. Patatin-like phospholipase domain containing 2 (PNPLA2) catalyzes the rate-limiting hydrolysis of TAG to free fatty acids (FFA). Meanwhile, peroxisome proliferator-activated receptor α/δ (PPARα/δ) promote fatty acid oxidation and inhibit inflammatory response, and are activated by FFA released during lipolysis. Given this regulatory interplay, the study investigates the hepatic status of PNPLA2, PPARα/δ signaling and PNPLA2-associated regulatory factors. The results showed that fatty liver cows exhibited a severe inflammatory response in the liver. In addition, hepatic mRNA and protein levels of PNPLA2, phosphorylated hormone-sensitive lipase, and monoacylglycerol lipase were reduced in the fatty liver cows compared with healthy cows, while those of G0/G1 switch protein 2 (G0S2) and abhydrolase domain-containing 5, lysophosphatidic acid acyltransferase (ABHD5) were not significantly different between the two groups. Notably, the hepatic transcriptional activities of PPARα and PPARδ were significantly lower in cows with fatty liver than in healthy cows. In summary, the present data indicated that fatty liver cows exhibited hepatic inhibition of the PNPLA2-PPARα/δ signaling axis and a marked inflammatory response, which may be a key factor triggering and exacerbating fatty liver. These findings not only contribute to the mechanistic insights into bovine fatty liver development but also highlight the PNPLA2-PPARα/δ signaling axis as a potential target for therapeutic intervention.

Triphenyltin (TPT), a widely utilized organotin compound, serves marine, agricultural, and industrial applications. TPT is commonly found in estuaries and coastal regions. However, recent studies on environmental pollution have identified TPT as a pollutant due to its pronounced pollutant characteristics and potential implications for human health. Research from the past has demonstrated that TPT can cause issues with lipid metabolism. However, the specific metabolites affected and the involvement of the PPAR pathway remain unknown. Herein, male Sprague-Dawley (SD) rats received oral administration of TPT at daily doses of 0.5, 1, and 2 mg/kg for a period of 28 days. To investigate the abnormal metabolism in TPT-exposed rats, liver samples were analyzed using LC-MS/MS non-targeted metabolomics. Validated in vitro experiments were also performed using BRL-3A cells. This study suggests that exposure to TPT causes liver injury, increases lipid accumulation, and alters PPARγ expression levels. The findings highlight the need for restrictions on its use and further investigation of its toxic effects on other organs and systems to better assess its potential impact on human health.

Mitochondrial dysfunction, often linked to the deregulation of mitochondrial biogenesis, plays a significant role in the progression of neurological diseases. Dexmedetomidine (Dex), a selective alpha-2 adrenergic agonist utilized for anesthesia and sedation, has a largely unexplored impact on mitochondrial function. In this study, cells were treated with Dex at concentrations of 10 μg/mL and 20 μg/mL. Mitochondrial function was assessed by measuring mitochondrial membrane potential, adenosine triphosphate (ATP) production, and oxygen consumption rates. The expression levels of key mitochondrial genes and proteins were analyzed using quantitative polymerase chain reaction (qPCR) and Western blot. To investigate the role of AMP-activated protein kinase α (AMPK), cells were co-treated with the AMPK inhibitor Compound C. Our results demonstrate that treating cells with Dex significantly enhances mitochondrial membrane potential, ATP production, and oxygen consumption rates. Additionally, Dex increases the expression of vital mitochondrial genes, including Mitochondrially Encoded NADH: Ubiquinone Oxidoreductase Core Subunit 6 (mtND6), Mitochondrially Encoded Cytochrome c Oxidase II (mtCO2), and Mitochondrially Encoded ATP Synthase 6 (mtATP6), while also improving the mtDNA-to-nDNA ratio. The treatment raises Messenger Ribonucleic Acid (mRNA) and protein levels of essential mitochondrial biogenesis regulators such as Nuclear Respiratory Factor 1(Nrf1), Mitochondrial Transcription Factor A (TFAM), Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1α (PGC-1α), and phosphorylated AMP-Activated Protein Kinase α (p-AMPKα). However, when cells are co-treated with the AMPK inhibitor compound C, these positive effects are lost, highlighting the necessity of AMPK activation for the mitochondrial enhancements induced by Dex. These findings suggest a promising therapeutic potential for Dex in supporting neuronal function through mitochondrial pathways.

Perfluorooctanoic acid (PFOA) is a persistent organic pollutant (POP) that can accumulate in living organisms and cause damage to multiple organs and systems in the human body. The kidney is viewed as a key organ affected by PFOA, but the exact mechanism by which PFOA exposure causes kidney damage remains unclear. We selected data from 13,804 participants aged > 12 years old from the National Health and Nutrition Examination Survey (NHANES) database from 2003 to 2018 to analyze the relationship between PFOA and kidney injury. In addition, in the animal experiment, twenty adult male SD rats were divided into four groups randomly: one control group and three PFOA-treated groups. The experiment lasted 28 days, during which time water consumption and urine output were recorded daily. Kidney tissue samples were collected at the end of the experiment. Biochemical assays, RT-qPCR and Western blotting techniques were used to investigate the toxic effects of PFOA exposure on the kidney. Analysis of NHANES data shows a positive correlation between serum PFOA and uric acid (UA) with a β-value of 0.23 (95 % CI: 0.18-0.27) in Model 2. In animal studies, PFOA significantly affected rats' water intake (increased at 5 mg/kg/d, decreased at 20 mg/kg/d) and urine output (5 > 1.25 > 20 mg/kg/d > control). Renal biochemical analyses revealed significantly lower total cholesterol (TC) (1.25, 20 mg/kg/d groups) and triglyceride (TG) (1.25, 5 mg/kg/d groups) in PFOA-exposed rats. The peroxisome proliferator-activated receptors (PPAR) pathway-related gene/protein levels were significantly altered, such as 900 differentially expressed genes (DEGs) in the 20 mg/kg/d group and upregulated ACOT1 in all PFOA groups. In conclusion, the present study confirms that exposure to PFOA leads to increased oxidative catabolism of fatty acids and impaired renal lipid metabolism. These findings provide an important basis for elucidating the potential health hazards of PFOA.

Bisphenol AF (BPAF) is a widespread endocrine disruptor in the environment, and the use of BPAF has been strongly associated with the development of several diseases. In this study, we investigated the effects of BPAF on growth, development, oxidative stress and lipid metabolism in zebrafish. We chose the concentrations based on the measured LC50 at 96 h post-fertilization (96 hpf), and the zebrafish embryos were exposed to three different concentrations (0.125, 0.5 and 2 mu mol/L). The findings indicated that BPAF exposure in zebrafish leaded to alterations in heart rate, body length and hatching rate, as well as an accumulation of red blood cells in the heart. Additionally, BPAF exposure resulted in increased levels of neutrophils, reactive oxygen species (ROS) and malondialdehyde (MDA), and decreased activity of antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)), thus disturbing the balance between oxidative and antioxidative systems. BPAF promoted fatty acid catabolism and inhibited fatty acid synthesis, ultimately leading to a reduction in fatty acid content. Mechanistically, RNA-seq analysis and RT-qPCR revealed a significant upregulation of heat shock protein 70 (hsp70) after BPAF exposure. Inhibition of hsp70 with VER-155008 ameliorated BPAF-induced oxidative stress. These data provided a novel approach to investigate BPAF-induced oxidative stress and suggested that regulation of hsp70 is a crucial target for alleviating this process.

Bisphenol F (BPF) is one of the main substitutes for Bisphenol A (BPA) and is widely used in the manufacture of household products. In addition, BPF threatens human health through environmental pollution and the food chain. However, the hepatotoxicity of BPF and its effects on glucose and lipid metabolism remain unclear. This study used male SD rats as an animal model to investigate the hepatotoxicity of BPF and its effects on glucose and lipid metabolism. The results of the HE staining, serum and liver biochemical indicators show that BPF can damage the basic structure of the liver, cause liver dysfunction and lead to disorders of liver glucose metabolism and lipid metabolism. Furthermore, we conducted metabolomics and proteomics analyses on the livers of the BPF exposed group at 100 mg/kg/d in comparison with the control group. The results indicated that BPF exposure had a significant effect on liver metabolism. Combined with biological analysis and the validation of changes in genes and proteins related to glucose and lipid metabolism in the liver, it was elucidated that BPF can promote fatty acid oxidation and inhibit fatty acid synthesis through the AMPK and PPAR signaling pathways, leading to a reduction in fatty acids. Furthermore, it has been demonstrated that BPF can promote glycogen synthesis and gluconeogenesis via the AKT pathway, which can result in disorders of glucose metabolism.

As an alternative to perfluorooctanoic acid (PFOA), Hexafluoropropylene oxide trimer acid (HFPO-TA), is currently utilized across various industries and national life, and now, has been detected in all surroundings. Due to its widespread environmental presence and potential biological toxicity, it may adversely affect human health. Studies have shown that HFPO-TA exposure exhibits hepatotoxicity, however, the underlying mechanisms remain unclear. This study investigated the mechanisms of HFPO-TA induced hepatic oxidative stress and lipid peroxidation leading to hepatotoxicity and ferroptosis through in vivo and in vitro experiments. In the in vivo experiments, mice were exposed to 0.02, 0.1 and 0.5 mg/kg/d of HFPO-TA for 14 days, which induced hepatic oxidative stress, mitochondrial morphological changes and lipid peroxidation, leading to hepatocyte ferroptosis. In vitro experiments with AML12 cells demonstrated that HFPO-TA exposure resulted in the accumulation of reactive oxygen species (ROS), a decrease in mitochondrial membrane potential, and subsequent lipid peroxidation and cell membrane damage, ultimately causing ferroptosis. In conclusion, both in vivo and in vitro experiments provide preliminary evidence implicating the p62/Keap1/Nrf2 pathway in HFPO-TA-induced oxidative stress, increases the accumulation of lipid peroxidation products, and leads to the injury of liver tissue and AML12 cells. This study provides new insights into the hepatotoxic effects of HFPO-TA.

The accumulation of perfluorooctanoic acid (PFOA) and its substitutes hexafluoropropylene oxide dimer acid (HFPO-DA, trade name Gen-X) and hexafluoropropylene trimer acid (HFPO-TA), which are widely used synthetic chemicals, may pose significant health risks across species. This study systematically investigated the multi-dimensional effects of PFOA and its substitutes on fatty acid metabolic processes and erythrocyte survival through bioinformatic and metabolomics analysis, complemented by a variety of zebrafish exposure experiments, including Oil Red O staining (ORO staining), Nile red staining (NR staining), 1,3-bis(diphenylphosphino)propane (DPPP) and reactive oxygen species (ROS), as well as inflammation, apoptosis and gene expression assays. PFOA and its substitutes significantly disrupted fatty acid oxidation degradation and synthesis, by interfering with the peroxisome proliferator-activated receptor α (PPARα) signaling pathway, leading to lipid accumulation in zebrafish. In addition, PFOA and HFPO-TA reduced the number of erythrocytes in zebrafish through excessive generation of ROS and abnormal activation of the tp53 gene. Gene expression analysis further confirmed that the expression of genes related to fatty acid metabolism, inflammation and apoptosis regulated by PPARα and its target genes were significantly upregulated. This study revealed that PFOA and its substitutes exert multi-dimensional effects on fatty acid metabolism and erythrocyte survival in zebrafish through the activation of PPARα, providing new perspectives for understanding the toxicity mechanisms of per- and polyfluoroalkyl substances (PFAS).

Hexafluoropropylene oxide trimer acid (HFPO-TA) is an emerging environmental pollutant that can accumulate in air and surface water. Currently, it has been widely used in fluoropolymer industry, which could cause serious environmental pollution. Due to the high bioaccumulation, the accumulation of pollutants may have an adverse effect on the normal physiological function of the kidneys. However, the toxic effects of HFPO-TA on the kidney are unknown. In this study, we investigated the toxic effects of HFPO-TA exposure on the rat kidney and its mechanism of action. Male SD rats were divided into 4 groups: control group (Ctrl group), L group (0.125 mg/kg/d), M group (0.5 mg/kg/d) and H group (2 mg/kg/d). After 14 consecutive days of gavage, periodic acid‑silver methenamine (PASM) and hematoxylin-eosin (HE) staining were used to examine the structure of the kidneys. We also used transcriptome sequencing (RNA-seq) to identify differentially expressed genes (DEGs) in the testes of rats in both the control and high dose groups. Besides, expression of key proteins was analyzed by immunohistochemistry. The results indicated that HFPO-TA can lead to injured renal capsule, change glomerular shape and have a significant impact on the protein expression levels of AQP2, p-AQP2 and PPARα. Additionally, the level of total cholesterol (TC) was obviously decreased after HFPO-TA exposure. RNA-seq analysis showed that HFPO-TA primarily affected peroxisome proliferator-activated receptor (PPAR) signaling pathway that is associated with lipid metabolism and cyclic adenosine monophosphate (cAMP) signaling pathway. In summary, exposure to HFPO-TA can lead to kidney damage and lipid metabolism disorders.

The ability to accurately analyze perfluoroalkyl substance (PFAS) levels in beef is imperative in order to effectively assess food-safety risks and ensure consumer safety because PFASs are harmful and prevalent in beef. In this study, we developed a rapid and accurate method for the simultaneously determination of the 17 PFASs in beef using dispersive solid-phase extraction (d-SPE) and ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and optimized the mobile phase system, extraction solvent, and d-SPE materials. Samples were finally extracted using 0.1% (v/v) formic acid in acetonitrile, cleaned using d-SPE with PSA, C18, GCB, and EMR-Lipid, separated using an Acquity Premier BEH C18 column (100 mm×2.1 mm, 1.7 μm) with 0.5 mmol/L ammonium fluoride aqueous solution and methanol as the mobile phases at a flow rate of 0.3 mL/min. Analytes were detected in negative ion switching mode (ESI-) with multiple reaction monitoring (MRM) scanning, and quantitatively analyzed using the internal standard method. The 17 PFASs exhibited linearity in the 0.2-20.0 μg/L range under the optimal experimental conditions, with correlation coefficients of 0.9915-0.9999. The method delivered limits of detection (LODs) of 0.003-0.007 μg/kg and limits of quantification (LOQs) of 0.01-0.02 μg/kg. The 17 PFASs exhibited recoveries of 71.1%-127.4% with RSDs of 0.6%-14.4% when spiked at three levels (0.05, 0.5, and 1.8 μg/kg). We optimized the mobile phase system, which revealed that, compared with 2.0, 5.0, and 10.0 mmol/L ammonium formate or ammonium acetate in aqueous methanol, 0.5 mmol/L ammonium fluoride in aqueous methanol exhibited higher sensitivities for all the 17 PFASs, with PFASs bearing long-chain carboxylic acids (C10-C18) showing 1-2 fold increases in sensitivity. PFASs do not dissociate in acidic environments, favoring their entry into the organic phase. Therefore, we investigated the effect of extractant acidity, which revealed that the 17 PFASs were better extracted using 0.1% (v/v) formic acid in acetonitrile. The beef matrix has a complex composition; consequently, d-SPE adsorbents were required to purify samples and reduce matrix effects. The purification effects of four adsorbents (PSA, C18, GCB, and EMR-Lipid) toward the 17 PFASs and the amount of EMR-Lipid used were investigated, which revealed that 100 mg PSA+80 mg C18+40 mg GCB+150 mg EMR-Lipid exhibited superior matrix-purification behavior. We also investigated the effects of various injection solutions and types of syringe filter, with pure methanol selected for reconstitution and high-speed supernatant centrifugation applied prior to injection. The developed method is simple, rapid, sensitive, and reproducible, and can be used to simultaneously, rapidly, and accurately determine various perfluoroalkyl compounds in beef.

Changes in modern lifestyles have led to an increase in obesity rates. Excessive lipid accumulation leads to abnormal cholesterol metabolism, and maintaining a balanced cholesterol metabolism is essential for the normal functioning of cells and the body. Rutin belongs to the group of flavonoids with hypolipidemic, anti-inflammatory and antioxidant effects. The aim of this study was to investigate the role of rutin in cholesterol metabolism disorders induced by a high cholesterol diet in zebrafish larvae. The trial was divided into five groups: Normal diet (ND), 5 % high cholesterol diet (HCD), 5 % high cholesterol diet with 80 mu g/g ezetimibe diet (EZE), 5 % high cholesterol diet with 5 % rutin diet (RL-HCD), and 5 % high cholesterol diet with 10 % rutin diet (RH-HCD). Zebrafish larvae at 5 dpf were randomly divided into five groups and continuously fed different diets for 10 days, after 10 days zebrafish samples were collected for subsequent experiments. Body length, body width, oil red O, and Nile red staining were measured to detect biochemical indexes, analyze inflammatory response and lipid accumulation. Vascular endothelial injury was assessed by stereofluorescence microscopy and ELISA. In order to study the protective effect of rutin in zebrafish with cholesterol metabolism disorder induced by HCD, RNA-seq and LC-MS/MS nontargeted metabolomics were employed. The results indicate that HCD led to an increase in the body length and width of zebrafish. The HCD group induced an increase in body length and width, lipid accumulation, and exacerbated inflammation. Additionally, vascular damage and abnormal expression of endothelial cell markers were observed. Rutin lowered lipid levels in zebrafish fed an HCD, reduced inflammation, and protected endothelial cells. The RNA-seq and metabolomic analysis combined demonstrated that rutin effectively ameliorates the disorder of cholesterol metabolism in vivo by reducing cholesterol synthesis and promoting cholesterol transport.

Perfluorooctanoic acid (PFOA) is a persistent environmental pollutant that can accumulate in the kidneys and eventually cause kidney damage. Rutin (RUTIN) is a natural flavonoid with multiple biological activities, and its use in against kidney damage has been widely studied in recent years. It is not yet known whether rutin protects against kidney damage caused by PFOA. In this study, 30 ICR mice were randomly divided into three groups: CTRL group, PFOA group and PFOA+RUTIN group. The mice were fed continuously by gavage for 28 days. Renal pathological changes were assessed by HE and PASM staining, and serum renal function and lipid indicators were measured. RNA-seq and enrichment analysis using GO, KEGG and PPI to detect differential expression of genes in treatment groups. Kidney tissue protein expression was determined by Western blot. Research has shown that rutin can improve glomerular and tubular structural damage, and increase serum CREA, HDL-C levels and decrease LDH, LDL-C levels. The expression of AQP1 and ACOT1 was up-regulated after rutin treatment. Transcriptomic analysis indicated that PFOA and rutin affect the transcriptional expression of genes related to lipid metabolism and oxidative stress, and may affected by PI3K-Akt, PPAR, NRF2/KEAP1 signaling pathways. In conclusion, rutin ameliorated renal damage caused by PFOA exposure, and this protective effect may be exerted by ameliorating oxidative stress and regulating lipid metabolism.

Triphenyltin (TPT) is a widely used pesticide that has a negative impact on biological health and production efficiency. In addition, TPT poses a threat to human health through the food chain and environmental pollution. However, the exact mechanism of TPT toxicity remains unclear. In this study, we investigated the hepatotoxicity of TPT and its effects on lipid metabolism using male SD rats as an animal model. Our results from HE and serum biochemical analysis suggested that TPT could damage liver structure and function, resulting in disruption of lipid metabolism. We therefore proceeded to analyze the proteomic response of rat liver tissue after 28 days of treatment with 2 mg/kg/d TPT. Our study demonstrates that TPT has a variety of effects on liver protein expression in rats. Through bioinformatic analysis, we observed significant changes in proteins related to fatty acid oxidation and synthesis due to TPT exposure. Furthermore, western blot and RT-qPCR experiments confirmed that TPT can affect lipid metabolism through the PPAR pathway. These findings suggest that TPT exposure can lead to liver damage, lipid accumulation and metabolic disorders.

Triphenyltin (TPT) is a class of organotin compounds that are extensively used in industry and agriculture. They have endocrine-disrupting effects and cause severe environmental contamination. Pollutants may accumulate in the kidneys and cause pathological complications. However, the mechanism of TPT's toxicological effects on the kidney remains unclear. This study aimed to investigate the toxic effects and mechanism of action of TPT exposure on renal impairment in rats. Male SD rats were divided into four groups: the Ctrl group (control group), TPT-L group (0.5 mg/kg/d), TPT-M group (1 mg/kg/d), and TPT-H group (2 mg/kg/d). After 28 days of exposure to TPT, we observed the morphology and structure of kidney tissue using HE, PASM, and Masson staining. We also detected serum biochemical indexes, performed transcriptome sequencing of rat kidney tissue using RNAseq. Furthermore, protein expression levels were measured through immunohistochemistry and gene expression levels were determined using RT-qPCR. The study results indicated a decrease in kidney weight and relative kidney weight after 28 days of exposure to TPT. Additionally, TPT caused damage to kidney structure and function, as evidenced by HE staining, PASM staining, and serum biochemical tests. Transcriptomics identified 352 DEGs, and enrichment analyses revealed that TPT exposure primarily impacted the renin-angiotensin system (RAS). The expression levels of water channel proteins were reduced, and the expression levels of RAS and lipid metabolism-related genes (Mme, Ace, Fasn, Cyp4a8, Cpt1b and Ppard) were significantly decreased in the TPTtreated group. In summary, exposure to TPT may impair renal structure and function in rats by affecting RAS, AQPs, and lipid metabolism.

PFOA is one of the most representative compounds in the family of perfluorinated organic compounds. Due to its varying toxicity, alternatives to PFOA are beginning to emerge. HFPO-TA is an alternative for PFOA. It is currently unclear whether HFPO-TA affects glucose and lipid metabolism. In this study, rats were used as an animal model to investigate the effects of HFPO-TA on liver glucose and lipid metabolism. We found that HFPO-TA can affect glucose tolerance. Through omics analysis and molecular detection, it was found that HFPO-TA mainly affects the PPAR signaling pathway in the liver of rats, inhibiting liver glycolysis while promoting glucose production. HFPO-TA not only promotes the synthesis of fatty acids in the liver, but also promotes the breakdown of fatty acids, which ultimately leads to the disruption of hepatic glucose and lipid metabolism. The effects of HFPO-TA on metabolism are discussed in this paper to provide a reference for the risk assessment of this PFOA substitute.

Perfluorononanoic acid (PFNA) is a perfluoroalkyl acid containing nine carbon chains, with an additional carbon‑fluorine bond that makes it more stable and toxic. Studies have shown that PFNA can harm the reproductive, immune, and nervous systems, as well as many organs, which can increase the risk of cancer. In this study, zebrafish embryos were treated with 0 and 100 μM PFNA for 72 and 96 hpf, and their angiogenesis and haematopoiesis were observed under laser confocal microscopy using Tg (fli1:EGFP) and Tg (gata1:DsRed) transgenic zebrafish. The data showed that PFNA exposure decreased heart rate and slowed blood flow in zebrafish. PFNA was found to inhibit erythropoiesis by O-dianisidine staining. RNA-seq analysis was used to compare gene expression changes in zebrafish from control and 100 μM PFNA-exposed groups at 72 hpf. KEGG results showed significant enrichment of PPAR signaling pathway, fatty acid metabolism, steroid biosynthesis and apoptosis. The RNA-seq results were validated by real-time fluorescence quantitative PCR (RT-qPCR). Oil red O staining and Filipin staining showed increased lipid accumulation after PFNA exposure, and TUNEL staining showed that PFNA exposure led to apoptosis. In conclusion, exposure to PFNA may cause toxic effects in zebrafish by affecting cardiovascular development, causing lipid accumulation and promoting apoptosis.

BACKGROUND:TPT is an environmental endocrine disruptor that can interfere with endocrine function. However, whether TPT can cause damage to liver structure and function and abnormal lipid metabolism and whether it can cause ER stress is still unclear. OBJECTIVE:To explore the effect of TPT on liver structure, function and lipid metabolism and whether ER stress occurs. METHODS:Male SD rats were divided into 4 groups: control group (Ctrl group, TPT-L group (0.5 mg/kg/d), TPT-M group (1 mg/kg/d), and TPT-H group (2 mg/kg/d). After 10 days of continuous gavage, HE staining was used to observe the morphological structure of liver tissue, serum biochemical indicators were detected, gene expression and functional enrichment analysis were performed by RNA-seq, Western Blot was used to detect the protein expression level of liver tissue, and qRT-PCR was used to detect the gene expression. RESULTS:After TPT exposure, the liver structure damaged; serum TBIL, AST and m-AST levels were significantly increased in the TPT-M group, and serum TG levels were significantly decreased in the TPT-H group. TCHO and TG in liver tissues were significantly increased; transcriptomic analysis detected 105 differential genes. Enrichment analysis showed that TPT exposure mainly affected fatty acid metabolism and drug metabolism in liver tissue, and also affected the redox process of liver tissue; the protein expression levels of PPARα, PPARγ, AMPK, RXRα, IRE1α and PERK were significantly increased after TPT exposure; the expression levels of lipid metabolism-related genes Acsl1, Elovl5, Hmgcr, Hmgcs1 and Srebf1 were significantly increased in the TPT-L group, while in the TPT-M and TPT-H groups had no significant change. CONCLUSIONS:TPT exposure can cause liver injury, lipid metabolism disorder and ER stress.