Mode-of-action and human relevance framework analysis for rat Leydig cell tumors associated with sulfoxaflor

Rasoulpour, Reza J.; Terry, Claire; LeBaron, Matthew J.; Stebbins, K. E.; Ellis-Hutchings, Robert G.; Billington, Richard

doi:10.3109/10408444.2014.910750

Cited by 21 publications

(5 citation statements)

References 40 publications

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“…While Leydig cell tumours occur frequently in rats and mice, they are diagnosed rarely in humans. This is largely due to quantitative and qualitative species differences in Leydig cell response to hormonal stimuli (Rasoulpour et al, 2014). In rodents, there are several modes of actions for the induction of this tumour by chemical compounds.…”

Section: Testismentioning

confidence: 99%

Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food

Knutsen¹,

Alexander²,

Barregård³

et al. 2018

EFS2

180

199

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The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in food. Regarding PFOS and PFOA occurrence, the final data set available for dietary exposure assessment contained a total of 20,019 analytical results (PFOS n = 10,191 and PFOA n = 9,828). There were large differences between upper and lower bound exposure due to analytical methods with insufficient sensitivity. The CONTAM Panel considered the lower bound estimates to be closer to true exposure levels. Important contributors to the lower bound mean chronic exposure were 'Fish and other seafood', 'Meat and meat products' and 'Eggs and egg products', for PFOS, and 'Milk and dairy products', 'Drinking water' and 'Fish and other seafood' for PFOA. PFOS and PFOA are readily absorbed in the gastrointestinal tract, excreted in urine and faeces, and do not undergo metabolism. Estimated human half-lives for PFOS and PFOA are about 5 years and 2-4 years, respectively. The derivation of a health-based guidance value was based on human epidemiological studies. For PFOS, the increase in serum total cholesterol in adults, and the decrease in antibody response at vaccination in children were identified as the critical effects. For PFOA, the increase in serum total cholesterol was the critical effect. Also reduced birth weight (for both compounds) and increased prevalence of high serum levels of the liver enzyme alanine aminotransferase (ALT) (for PFOA) were considered. After benchmark modelling of serum levels of PFOS and PFOA, and estimating the corresponding daily intakes, the CONTAM Panel established a tolerable weekly intake (TWI) of 13 ng/kg body weight (bw) per week for PFOS and 6 ng/kg bw per week for PFOA. For both compounds, exposure of a considerable proportion of the population exceeds the proposed TWIs.

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Section: Testismentioning

confidence: 99%

Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food

Knutsen¹,

Alexander²,

Barregård³

et al. 2018

EFS2

180

199

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“…It has been widely and clinically used. β-HCG is the most important index for treatment of trophocytes and follow-up visits [29, 30] and closely associated with the therapeutic effect. The experimental result has shown that the serum β-HCG decreases significantly after the action of drug, which further demonstrating the role of puerarin in inhibiting the transplanted tumor of the SCID mice with human choriocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

Effect of puerarin on human choriocarcinoma cells

Liu

Wang

et al. 2015

Open Medicine

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ObjectiveTo discuss the effect of puerarin on human choriocarcinoma cells.MethodsSurvival rates under puerarin monotherapy, fluorouracil (5-FU) monotherapy and puerarin in combination with 5-FU were detected by MTT assay. Apoptotic morphology was observed with Hoechst 33258 staining. Apoptosis rates were detected with flow cytometry. Expressions of AKT, mechanistic target of rapamycin (mTOR), and P70S6K mRNAs and phosphorylated proteins were detected by RT-PCR and Western blot. Tumor-bearing mice were administered puerarin and puerarin+5-FU, and serum levels of β-human chorionic gonadotropin (β-HCG) were measured.ResultsProliferation inhibition and apoptosis rates of JEG-3 cells were positively correlated with puerarin concentration, which increased in the puerarin+5-FU group. Expression levels of AKT, mTOR, P70S6K mRNAs, and phosphorylated proteins decreased significantly after action of puerarin at different concentrations. With increasing puerarin concentration, expression of cleaved-caspase-3 in JEG-3 cells increased, whereas that of Bcl-2 decreased. Puerarin significantly inhibited tumor growth in choriocarcinoma-bearing SCID mice. Serum β-HCG levels were significantly lower than those of control group after administration. Magnitude of β-HCG decline was positively correlated with concentration..ConclusionPuerarin+5-FU inhibited proliferation of JEG-3 choriocarcinoma cells and promoted their apoptosis, being associated with the mTOR signaling pathway.

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“…There are limited studies related to the acute and chronic toxic effects of sulfoxaflor on mammalian species. These studies reported that sulfoxaflor may also have carcinogenic [27,28] and teratogenic effects in mammals [29].…”

Section: Introductionmentioning

confidence: 99%

Fucoidan Protects against Acute Sulfoxaflor-Induced Hematological/Biochemical Alterations and Oxidative Stress in Male Mice

2021

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Fucoidan is a sulfated polysaccharide which can be found among a number of macroalgea species. It has a broad spectrum of biological activities including anti-oxidant, anti-tumor, immunoregulation, anti-viral and anti-coagulant. The current study was performed to investigate possible protective effects of fucoidan for sulfoxaflor-induced hematological/biochemical alterations and oxidative stress in the blood of male Swiss albino mice. For this purpose, sulfoxaflor was administered at a dose of 15 mg/kg/day (1/50 oral LD50), and fucoidan was administered at a dose of 50 mg/kg/day by oral gavage alone and combined for 24 h and 7 days. Hematological parameters (RBC, HGB, HCT, MCV, MCH, MCHC, Plt, WBC, Neu, Lym and Mon), serum biochemical parameters (AST, ALT, GGT, LDH, BUN, Cre and TBil), and serum oxidative stress/antioxidant markers (8-OHdG, MDA, POC and GSH) were analyzed. The results indicated that sulfoxaflor altered hematological and biochemical parameters and caused oxidative stress in mice; fucoidan ameliorated some hematological and biochemical parameters and exhibited a protective role as an antioxidant against sulfoxaflor-induced oxidative stress.

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Mode-of-action and human relevance framework analysis for rat Leydig cell tumors associated with sulfoxaflor

Cited by 21 publications

References 40 publications

Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food

Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food

Effect of puerarin on human choriocarcinoma cells

Fucoidan Protects against Acute Sulfoxaflor-Induced Hematological/Biochemical Alterations and Oxidative Stress in Male Mice

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