Attenuation of perfluorooctanoic acid-induced testicular oxidative stress and apoptosis by quercetin in mice

Yuan, Yangyang; Ge, Shuna; Lv, Zehui; Wu, Mei; Kuang, Haibin; Yang, Bei; Yang, Jianhua; Wu, Lei; Wu, Zhongze; Zhang, Dalei

doi:10.1039/c7ra09036f

Cited by 13 publications

(10 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Quercetin (purity ≥95%, high performance liquid chromatography) purchased from Sigma-Aldrich Co. (St Louis, MO, USA) was dissolved in DMSO and the dosages of quercetin chosen were based on previous reports 23,25,26. Commercial kits for urine albumin, urine creatinine, blood urea nitrogen, and serum creatinine were purchased from Jiancheng Biotechnology Company (Nanjing, China).…”

Section: Methodsmentioning

confidence: 99%

<p>Quercetin improves lipid metabolism via SCAP-SREBP2-LDLr signaling pathway in early stage diabetic nephropathy</p>

Jiang

Wang

et al. 2019

DMSO

View full text Add to dashboard Cite

Purpose: Quercetin, the most widely distributed flavonoid, has been shown to have multiple properties and beneficial effects on various metabolic diseases. Thus, our aim was to investigate the underlying mechanism whereby quercetin regulates renal lipid accumulation and ameliorates early diabetic renal injuries in Lepr db /Lepr db (db/db) mice, a model of type 2 diabetes. Methods: db/db mice were administered either 50 mg/kg or 100 mg/kg quercetin by oral gavage once a day to evaluate its effects on early stage diabetic nephropathy; mice were sacrificed at the end of the 10th week after intervention; a similar number of db/db and db/m mice were used as controls. During the experimental study, the general status of the animals was observed daily; body weight and blood glucose concentrations were measured at bi-weekly intervals. Biochemical parameters of lipid metabolism were measured by automatic biochemical analyzer. Renal function parameters were performed using commercial kits. Early renal histological changes and lipid accumulation were demonstrated by H&E staining and Oil-Red-O staining, respectively. Moreover, the expression of key proteins in the low-density lipoprotein receptors (LDLr)-SREBP-2-SREBP cSCAP signaling pathway in the kidneys of diabetic mice was detected by Western blot assay. Results: Compared with diabetic controls, quercetin not only ameliorated albuminuria and urinary albumin-to-creatinine ratio, but also decreased blood urea nitrogen and glucose, serum cholesterol, triglycerides, and low-density lipoprotein cholesterol, whereas it had no remarkable effect on the high-density lipoprotein cholesterol in diabetic db/db mice. Additionally, the evidently down regulated expression of LDLr, HMGCR, SREBP-2, and SCAP subsequently attenuated the renal lipid profile change and lipid droplet accumulation, resulting in the alleviation of renal injury of db/db mice. Conclusion: Quercetin safely and efficiently alleviates early diabetic renal injuries, possibly through improving the lipid metabolism via SCAP-SREBP2-LDLr signaling pathway.

show abstract

Section: Methodsmentioning

confidence: 99%

<p>Quercetin improves lipid metabolism via SCAP-SREBP2-LDLr signaling pathway in early stage diabetic nephropathy</p>

Jiang

Wang

et al. 2019

DMSO

View full text Add to dashboard Cite

show abstract

“…In mouse testis, the lowest dose tested of 2.5 mg/kg/day PFOA increased MDA and hydrogen peroxide levels, decreased the expression of the oxidant-sensitive transcription factor, Nrf2, and inhibited the activities of antioxidant enzymes (superoxide dismutase and catalase) [91]. PFOA also induces oxidative stress in a dose-dependent manner from 0.5 to 5 mg/kg/day in the mouse liver and pancreas [25], and a variety of tissues including rat pancreatic β-cells [92], mouse testes and epididymis [93], and mouse ovary [94]. Similarly, in vivo and in vitro studies have demonstrated that PFOS exposure results in oxidative stress, evidenced by the production of ROS, changes in antioxidant enzymes, elevation of lipid peroxidation products and changes in Nrf2 [32,[95][96][97].…”

Section: Induces Oxidative Stressmentioning

confidence: 99%

“…Animal Bioassay In Vitro PFOA Association: [85] Association: [88]; [91]; [25]; [92] Association: [86]; [87]; [89]; [90]; [93]; [94]; [100]; [101]; [102] Long-chain PFAS a PFOS Association: [85] Association: [95]; reviewed in [32]; reviewed in [97]; [99] Association: [86]; [96]; reviewed in [32]; reviewed in [97]…”

Section: Epidemiologicalmentioning

confidence: 99%

Application of the Key Characteristics of Carcinogens to Per and Polyfluoroalkyl Substances

Temkin

Hocevar

Andrews

et al. 2020

IJERPH

View full text Add to dashboard Cite

Per- and polyfluoroalkyl substances (PFAS) constitute a large class of environmentally persistent chemicals used in industrial and consumer products. Human exposure to PFAS is extensive, and PFAS contamination has been reported in drinking water and food supplies as well as in the serum of nearly all people. The most well-studied member of the PFAS class, perfluorooctanoic acid (PFOA), induces tumors in animal bioassays and has been associated with elevated risk of cancer in human populations. GenX, one of the PFOA replacement chemicals, induces tumors in animal bioassays as well. Using the Key Characteristics of Carcinogens framework for cancer hazard identification, we considered the existing epidemiological, toxicological and mechanistic data for 26 different PFAS. We found strong evidence that multiple PFAS induce oxidative stress, are immunosuppressive, and modulate receptor-mediated effects. We also found suggestive evidence indicating that some PFAS can induce epigenetic alterations and influence cell proliferation. Experimental data indicate that PFAS are not genotoxic and generally do not undergo metabolic activation. Data are currently insufficient to assess whether any PFAS promote chronic inflammation, cellular immortalization or alter DNA repair. While more research is needed to address data gaps, evidence exists that several PFAS exhibit one or more of the key characteristics of carcinogens.

show abstract

“…Increased NRF2-ARE signaling in rat testes and liver of frogs exposed to PFOA, with greater expression of downstream NRF2 antioxidative targets (e.g., superoxide dismutase, catalase, heme oxygenase-1), has been documented. 31,32 Other oxidative stress protective pathways include the upregulation of metallothionein proteins (MTs) as well as recruitment of heat shock proteins (HSPs). 33,34 Activation of the metal response element promotes transcription of MTs and was observed in response to several PFAS.…”

Section: Oxidative Stressmentioning

confidence: 99%

Exploring Potential Carcinogenic Activity of Per- and Polyfluorinated Alkyl Substances Utilizing High-Throughput Toxicity Screening Data

Singh

Hsieh

2021

Int J Toxicol

View full text Add to dashboard Cite

Per- and polyfluorinated alkyl substances (PFAS) are ubiquitous, persistent, and toxic chemicals that pose public health risks. Recent carcinogenicity concerns have arisen based on epidemiological studies, animal tumor findings, and mechanistic data. Thousands of PFAS exist; however, current understanding of their toxicity is informed by studies of a select few, namely, perfluorooctanoic acid and perfluorooctanesulfonic acid. Hence, the computational, high-throughput screening tool, the US EPA CompTox Chemical Dashboard’s ToxCast, was utilized to explore the carcinogenicity potential of PFAS. Twenty-three major PFAS that had sufficient in vitro ToxCast data and covered a range of structural subclasses were analyzed with the visual analytics software ToxPi, yielding a qualitative and quantitative assessment of PFAS activity in realms closely linked with carcinogenicity. A comprehensive literature search was also conducted to check the consistency of analyses with other mechanistic data streams. The PFAS were found to induce a vast range of biological perturbations, in line with several of the International Agency for Research on Cancer–defined key carcinogen characteristics. Patterns observed varied by length of fluorine-bonded chains and/or functional group within and between each key characteristic, suggesting some structure-based variability in activity. In general, the major conclusions drawn from the analysis, that is, the most notable activities being modulation of receptor-mediated effects and induction of oxidative stress, were supported by literature findings. The study helps enhance understanding of the mechanistic pathways that underlie the potential carcinogenicity of various PFAS and hence could assist in hazard identification and risk assessment for this emerging and relevant class of environmental toxicants.

show abstract

Attenuation of perfluorooctanoic acid-induced testicular oxidative stress and apoptosis by quercetin in mice

Abstract: Quercetin treatment attenuated PFOA-induced oxidative stress and apoptosis in the testes of mice.

Cited by 13 publications

References 45 publications

<p>Quercetin improves lipid metabolism via SCAP-SREBP2-LDLr signaling pathway in early stage diabetic nephropathy</p>

<p>Quercetin improves lipid metabolism via SCAP-SREBP2-LDLr signaling pathway in early stage diabetic nephropathy</p>

Application of the Key Characteristics of Carcinogens to Per and Polyfluoroalkyl Substances

Exploring Potential Carcinogenic Activity of Per- and Polyfluorinated Alkyl Substances Utilizing High-Throughput Toxicity Screening Data

Contact Info

Product

Resources

About