Thyroid, bradycardic and hypothermic effects of perfluoro‐n‐decanoic acid in rats

Langley, Albert E.; Pilcher, Gary D.

doi:10.1080/15287398509530675

Cited by 43 publications

(15 citation statements)

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“…The toxicity of this compound is expressed as severe hypophagia, drastic body weight loss with delayed lethality, and thymic and testicular atrophy ( 2 4 ) . It has also been reported that the circulating concentration of L-thyroxine in the rat decreased after administration of PFDA (5,6). Recently, the significance of this hypothyroxinemia was examined by determining the activity of hepatic enzymes responsive to alterations in thyroid status in rats treated with PFDA (7).…”

Section: Introductionmentioning

confidence: 93%

“…Recently, the significance of this hypothyroxinemia was examined by determining the activity of hepatic enzymes responsive to alterations in thyroid status in rats treated with PFDA (7). The incongruous pattern of activity of hepatic enzymes sensitive to thyroid hormone following the administration of PFDA to the rat was, however, not compatible with a decline in thyroid function at the cellular level as might be expected from the reduced level of L-thyroxine in the circulation (5,6). In fact, hepatic activity of malic enzyme (L-malate: NADP oxidoreductase [decarboxylating], EC 1.1.1.40), extensively used as a measure of thyroid hormone effect (&-lo), was markedly increased in PFDA-treated rats (7).…”

Section: Introductionmentioning

confidence: 96%

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Regulation of hepatic malic enzyme by perfluorodecanoic acid

Kelling

Rafelghemp

Drake

et al. 1986

J. Biochem. Toxicol.

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Perfluorodecanoic acid (PFDA) administration to adult male rats increased both the activity of hepatic malic enzyme and liver weight in a dose-dependent manner. Hepatomegaly and augmented activity of malic enzyme in liver were apparent within one day following PFDA administration and reached a plateau by three days posttreatment. Malic enzyme quantity per liver in PFDA-treated rats was elevated within one day following dosing and increased continually throughout five days posttreatment. Administration of PFDA to rats in the fed state also led to an increase in the specific activity of hepatic malic enzyme that peaked at three days following dosing. When compared to the fed condition, rats fasted for 48 hours had a decrease in both relative liver weight and the quantity of supernatant protein per liver. The total activity (U/liver) and specific activity of malic enzyme in the liver were also reduced in the fasted state. During the 24 hours after treatment in rats fasted for 48 hours, the body weight as well as the absolute and relative liver weight of animals receiving vehicle declined continuously in the absence of feed. Following the administration of PFDA to fasted rats, body weight was maintained until eight hours posttreatment but then declined at a rate similar to that found with the vehicle-treated group. Absolute and relative liver weight in PFDA-treated rats were increased significantly at eight hours posttreatment when compared to those receiving vehicle, and this increment was maintained throughout the rest of the 24 hours following dosing. While the activity and enzyme content of hepatic malic enzyme decreased in the vehicle-treated group, administration of PFDA to rats fasted for 48 hours prevented their decline. The specific activity of hepatic malic enzyme in 48 hours fasted rats receiving PFDA was also elevated significantly at 16 hours posttreatment. Thus, the administration of PFDA to the adult male rat in both the fed and fasted nutritional states was found to regulate hepatic malic enzyme by not only increasing enzyme quantity but also by augmenting the specific activity, (ie, catalytic state) of the enzyme.

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Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 96%

Regulation of hepatic malic enzyme by perfluorodecanoic acid

Kelling

Rafelghemp

Drake

et al. 1986

J. Biochem. Toxicol.

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“…However, these chemicals, which do not exist naturally, are only slightly biodegradable and persist in the environment (Yakata et al 2003). Some overviews of the monitoring and toxicological findings for PFCs (Lau et al 2007;Buck et al 2011;Kannan 2011) include studies of human blood (whole blood, plasma, and serum) (Olsen et al 2003;Kannan et al 2004;Calafat et al 2007) and that of wildlife, including fish, birds, and marine mammals (Tolls et al 1994;Giesy and Kannan 2001;Taniyasu et al 2003;Lehmler 2005;Sinclair et al 2006) as well as of their hepatotoxicity (Klaunig et al 2003;Shipley et al 2004), immunotoxicity (Yang et al 2000;Wan and Badr 2006), hormonal effects (Langley and Pilcher 1985;Maras et al 2006), reproductive toxicity (Peng et al 2010;Stump et al 2008), and developmental toxicity (Olsen et al 2009). …”

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confidence: 97%

Unique Physicochemical Properties of Perfluorinated Compounds and Their Bioconcentration in Common Carp Cyprinus carpio L.

Inoue

Hashizume

Yakata

et al. 2011

Arch Environ Contam Toxicol

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Carp (Cyprinus carpio L.) was exposed to perfluorinated compounds (PFCs)-perfluoroalkyl carboxylic acids (number of carbon atoms, C = 8, 11, 12, 14, 16, and 18) and perfluorooctane sulfonate (PFOS)-in bioconcentration tests to compare the bioconcentration factors (BCFs) and physicochemical properties of each specific compound. Despite having the same number of carbon atoms (C = 8), the BCFs of perfulorooctanoic acid (PFOA) and PFOS differed by more than two orders of magnitude (PFOA BCF = < 5.1 to 9.4; PFOS BCF = 720 to 1300). The highest BCFs were obtained from perfluorododecanoic acid (BCF = 10,000 to 16,000) and perfluorotetradecanoic acid (BCF = 16,000 to 17,000). The longest observed depuration half-lives were for perfluorohexadecanoic acid (48 to 54 days) and PFOS (45 to 52 days). The concentrations of PFCs were highest in the viscera, followed by the head, integument, and remaining parts of the test fish. PFCs concentrations in the integument, which was in direct contact with the test substances, were relatively greater than that of other lipophilic substance (hexachlorobenzene). It is likely that Clog P would be a better parameter than log K (ow) for the prediction of BCFs for PFCs. Threshold values for PFCs bioaccumulation potential (molecular weight = 700, maximum diameter = 2 nm) seemed to deviate from those generally reported because of the specific steric bulk effect of molecule size.

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“…Moreover, its serum elimination half-life lasts several years. PFDA has been reported to induce hypophagia and severe weight loss, bradycardia, hypothermia, and decreased serum thyroid hormone levels in rats910. So far, there is certainly a need for more data in the field of PFDA-induced cancers.…”

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confidence: 99%

Perfluorodecanoic acid stimulates NLRP3 inflammasome assembly in gastric cells

Zhou

Dong

Ziyan

et al. 2017

Sci Rep

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Perfluorodecanoic acid (PFDA), a perfluorinated carboxylic acid, presents in the environment and accumulates in human blood and organs, but its association with tumor promotion are not clear. Given that inflammation plays a significant role in the development of gastric malignancies, we evaluated the effects of PFDA on activation of the inflammasome and inflammation regulation in the gastric cell line AGS. When added to cell cultures, PFDA significantly stimulated IL-1β and IL18 secretion and their mRNA levels compared with control cells. By RT-PCR and western-blot we found that up-regulation of NLRP3 were associated with promotion of IL-1β and IL-18 production. Then expression variation of cIAP1/2, c-Rel and p52 were analyzed, the results demonstrated raised mRNA expression in all the tested genes concomitant with enhanced inflammasome activity after exposure to PFDA. Assays with cIAP2 siRNA and NFκB reporter provided additional evidence that these genes were involved in PFDA-induced inflammasome assembly. Furthermore, increased secretion of IL-1β and IL-18 were detected in stomach of PFDA-treated mice, disorganized alignment of epithelial cells and inflammatory cell infiltration were also observed in the stomach tissues upon PFDA treatment. This study reports for the first time that PFDA regulates inflammasome assembly in human cells and mice tissues.

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Thyroid, bradycardic and hypothermic effects of perfluoro‐n‐decanoic acid in rats

Cited by 43 publications

References 5 publications

Regulation of hepatic malic enzyme by perfluorodecanoic acid

Regulation of hepatic malic enzyme by perfluorodecanoic acid

Unique Physicochemical Properties of Perfluorinated Compounds and Their Bioconcentration in Common Carp Cyprinus carpio L.

Perfluorodecanoic acid stimulates NLRP3 inflammasome assembly in gastric cells

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