Perfluorooctanoic acid (PFOA) exposure induces renal filtration and reabsorption disorders via down-regulation of aquaporins.

Perfluorooctanoic acid (PFOA) exposure is associated with kidney dysfunction, however the exact mechanisms by which PFOA induces nephrotoxicity and the specific involvement of aquaporins (AQPs) in kidney tissue remains unclear. In this study, adult male Sprague-Dawley (SD) rats were exposed to PFOA by oral gavage for 28 days and compared with controls. Body weight, water intake and urine volume were recorded daily. At the end of the experiment, blood and kidney samples were collected, and serum urea, creatine and uric acid levels were assessed. The renal expression levels of water channel proteins AQP1, AQP3, AQP2 and p-AQP2 (Ser256) were observed by immunohistochemical staining, and the corresponding transcription levels were detected by Western blot and qRT-PCR. The results showed that PFOA exposure inhibited weight gain and increased water intake, urine volume, kidney weight and renal visceral index. PASM staining and transmission electron microscopy revealed pathological thickening of the glomerular capsule and basement membrane. Serum urea levels were increased, while serum creatine levels were decreased compared to controls. Additionally, the expression levels of AQP1, AQP3, AQP2 and p-AQP2 in kidney tissues were decreased, and the phosphorylation of AQP2 at Ser256 was inhibited. In conclusion, we demonstrate that PFOA exposure can damage the renal filtration barrier and reduce the expression level of AQPs in renal tissues, leading to renal filtration and reabsorption 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.

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.

Perfluorooctanoic acid-induced lipid metabolism disorder in SD rat liver and its effect on the expression of fatty acid metabolism-related proteins. / å ¨æ°Ÿè¾›é ¸å¯¹SDå¤§é¼ è‚è„‚è´¨ä»£è°¢ç´Šä¹±åŠè„‚è‚ªé ¸ä»£è°¢ç›¸å ³è›‹ç™½è¡¨è¾¾çš„å½±å“.

OBJECTIVES: Perfluorooctanoic acid (PFOA) can cause lipid metabolism disorders in animal body and affect the lipolysis and synthesis of fatty acids. Peroxisome proliferators-activated receptor (PPAR) plays an extremely important role in this process. This study aims to explore the effects of PFOA on liver lipid metabolism disorders in Sprague Dewley (SD) rats and the expression of PPAR. METHODS: A total of 40 male SD rats were randomly divided into 4 groups (n=10 in each group): a control group (ddH2O), a low-dose PFOA group [PFOA 1.25 mg/(kg·d)], a middle-dose PFOA group [PFOA 5.00 mg/(kg·d)], and a high-dose PFOA group [PFOA 20.00 mg/(kg·d)]. The rats were fed with normal diet, and PFOA exposure were performed by oral gavage for 14 days, and the rats were observed, weighted and recorded every day during the exposure. After the exposure, the blood was collected, and the livers were quickly stripped after the rats were killed. Part of the liver tissues were fixed in 4% paraformaldehyde for periodic acid-schiff (PAS) staining; the contents of HDLC, LDLC, TG, TC in serum and liver tissues, as well as the activities of their related enzymes were assayed; The expression levels of cyclic adenosine monophosphate-response element binding protein (Cbp), general control of amino acid synthesis 5-like 2 (Gcn5L2), peroxidation peroxisome proliferation factor activated receptor γ (PPAR), silent information regulator 1 (Sirt1) and human retinoid X receptor alpha 2 (Rxrα2) ) were detected by Western blotting. RESULTS: After 14 days of PFOA exposure, the PAS staining positive particles in the cytoplasm and nucleus of SD rats in the medium and high dose groups were significantly reduced compared with the control group. The serum levels of LDLC and TC in the low-dose and middle-dose groups were significantly reduced compared with the control group (all P<0.05), while the high-dose group showed an increasing tendency, without siginificant difference (P>0.05), there was no significant difference in HDLC and TG (both P>0.05). The activities of alkaline phosphatase (AKP) and alanine aminotransferase (ALT) were increased significantly (both P<0.05) compared with control group; the ratio of ALT/aspartate aminotransferase (AST) in the high-dose group was increased significantly (P<0.05), there was no significant difference in LDH and TG (both P>0.05); the HDLC content in the liver tissues in the high-dose group was significantly reduced, compared with the control group (P<0.05); the TC contents in the liver tissues in the low, medium and high-dose groups were significantly increased (all P<0.05), there was no significant difference in LDLC and TG (both P>0.05); the AKP activity in the livers in the medium and high-dose groups was significantly increased (both P<0.05), there was no siginificant difference in LDH, ALT, and the ratio of ALT/AST (all P>0.05); the protein expression levels of Ppar γ, Cbp and Rxrα2 in the liver in the high dose groups were significantly down-regulated compared with the control group (all P<0.05), while the protein expression levels of Sirt1 were significantly up-regulated (all P<0.05). CONCLUSIONS: PFOA exposure can cause lipid metabolism disorder and glycogen reduction in SD rat livers, which may be related to the activation of Sirt1 and inhibition of Ppar γ expression, leading to affecting the normal metabolism of fatty acids and promoting glycolysis.

[Effect of perfluorooctanoic acid on lipid accumulation in rat liver cells BRL-3A and its possible mechanism].

OBJECTIVE: To investigate the effect of perfluorooctanoic acid on rat hepatocytes BRL-3 A cell viability and the expression of transcription factor nuclear factor erythroid 2-related factor 2(Nrf2) and arginosuccinate synthase(Ass1). METHODS: Rat hepatocytes BRL-3 A were cultured and divided into control group(0 µmol/L PFOA), low-dose group(6.25 µmol/L PFOA), and medium-dose group(25 µmol/L PFOA), high-dose group(100 µmol/L PFOA). After 48 hours, cell viability was detected by MTT, ROS content was detected by free radical indicator H_2DCFDA, enzyme activity related to oxidative stress was detected by the kit, Nrf2 and Ass1 protein expression level was detected by Western blot and immunocytochemistry(ICC). RESULTS: Compared with the control group, with the increase of the PFOA concentration, the cell viability of the middle and high dose groups had a downward trend, but there was no statistical significance(P>0.05). The intracellular ROS content increased, among which in the middle and high dose groups significantly increased(P<0.05), and the average fluorescence intensity was(5417.66±161.09) and(5725.50±166.83), respectively. Compared with the control group, the content of intracellular TG, TC and MDA in the low and medium dose groups did not change significantly, and the content of TG, TC and MDA in the high dose group was significantly increased(P<0.05), which was(0.21±0.05) mmol/L, (14.5±6.07) mmol/L and(1.23±0.33) nmol/mL, respectively. According to the ICC and Western blot result, the expression level of Nrf2 protein increased significantly in the high-dose group(P<0.05), and the expression level of Ass1 protein increased significantly in the low-dose group(P<0.05). CONCLUSION: Exposure to a certain dose of PFOA can lead to the accumulation of ROS in BRL-3 A cells. Nrf2 and Ass1 can play a certain role in eliminating ROS and ammonia detoxification by increasing their expression under the oxidative damage of rat liver cells caused by PFOA.