Transcriptomics-based analysis reveals the nephrotoxic effects of triphenyltin (TPT) on SD rats by affecting RAS, AQPs and lipid metabolism.

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 RNA-seq. 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 TPT-treated group. In summary, exposure to TPT may impair renal structure and function in rats by affecting RAS, AQPs, and lipid metabolism.

TMT-based quantitative proteomics analysis of Sprague-Dawley rats liver reveals Triphenyltin induced liver damage and lipid metabolism disorders.

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.

Rutin ameliorate PFOA induced renal damage by reducing oxidative stress and improving lipid metabolism.

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.

PFOA exposure induces aberrant glucose and lipid metabolism in the rat liver through the AMPK/mTOR pathway.

Perfluorooctanoic acid (PFOA) is the most prominent member of a widely utilized family of compounds named Perfluoroalkyl substances (PFASs). Initially produced for use in both industrial and consumer applications, it has since been recognized that PFASs are extremely persistent in the environment where they have been characterized as persistent organic pollutants (POPs). While previous studies have demonstrated that PFOA may induce disorders of lipid and carbohydrate metabolism, the precise mechanisms by which PFOA produces this phenotype and the involvement of downstream AMPK/mTOR pathways remains unclear. In this study, male rats were exposed to 1.25, 5 and 20 mg PFOA/kg body weight/day for 28 days by oral gavage. After 28 days, blood was collected and tested for serum biochemical indicators and livers were removed and weighed. To investigate aberrant metabolism in rats exposed to PFOA, livers were analyzed by performing LC-MS/MS untargeted metabolomics, quantitative real-time PCR, western blotting, immunohistochemical staining was also performed on exposed tissues. Our results showed that exposure to PFOA induced liver damage, increased the expression of glucose and lipid related biochemical indexes in liver and serum, and altered the expression levels of AMPK/mTOR pathway related genes and proteins. In summary, this study clarifies the mechanisms responsible for PFOA toxicity in the liver of exposed animals.

Triphenyltin (TPT) exposure causes SD rat liver injury via lipid metabolism disorder and ER stress revealed by transcriptome analysis.

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.

Rutin ameliorates perfluorooctanoic acid-induced testicular injury in mice by reducing oxidative stress and improving lipid metabolism.

This study investigated the protective effect of rutin on reproductive and blood-testis barrier (BTB) damage induced by perfluorooctanoic acid (PFOA) exposure. In this study, male ICR mice were randomly divided into three groups, Ctrl group (ddH2O, 5 mL/kg), PFOA group (PFOA, 20 mg/kg/d, 5 mL/kg), PFOA + rutin group (PFOA, 20 mg/kg/d, 5 mL/kg; rutin, 20 mg/kg/d, 5 mL/kg). Mice were exposed to PFOA for 28 days by gavage once daily in the presence or absence of rutin. Histopathological observations demonstrated that rutin treatment during PFOA exposure can reduce structural damage to testis and epididymis such as atrophy of spermatogenic epithelium and stenosis of epididymal lumen, while increase in the number and layers of spermatogenic cells. Biochemical detection demonstrated that rutin can reduce 8-hydroxy-2'-desoxyguanosine (8-OHdG) concentration in the serum and testis tissues. Rutin can also ameliorate glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) content, and reduce malondialdehyde (MDA) and total cholesterol (TC) content in testis tissues. Biotin tracking immunofluorescence and transmission electron microscopy demonstrated that rutin can ameliorate BTB structural damage during PFOA exposure. Rutin ameliorated the stress expression of tight junction proteins occludin and claudin-11. In conclusion, our findings suggested that rutin has a degree of protection in reproductive and BTB damage, which could put forward a new perspective on the application of rutin to prevent reproductive damage.