The combined antiandrogenic effects of five commonly used pesticides

Birkhøj, Mia; Nellemann, Christine; Jarfelt, Kirsten; Jacobsen, Helene; Andersen, Helle Raun; Dalgaard, Majken; Vinggaard, Anne Marie

doi:10.1016/j.taap.2004.04.016

Cited by 95 publications

(68 citation statements)

References 28 publications

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“…Kojima et al (2004) examined the estrogenicity of 22 carbamate pesticides and found that methiocarb activates estrogen receptors (ER) α and β. The anti-androgenic activity of methiocarb has also been reported in two other studies (Birkhøj et al, 2004;Kojima et al, 2004). Recently, we reported the effect of the metabolic transformation of methiocarb and carbaryl on their estrogenic and anti-androgenic activities (Tange et al, 2016).…”

Section: Introductionsupporting

confidence: 68%

Metabolism of methiocarb and carbaryl by rat and human livers and plasma, and effect on their PXR, CAR and PPARα activities

et al. 2016

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-The oxidative, reductive, and hydrolytic metabolism of methiocarb and the hydrolytic metabolism of carbaryl by liver microsomes and plasma of rats or humans were examined. The effects of the metabolism of methiocarb and carbaryl on their nuclear receptor activities were also examined. When methiocarb was incubated with rat liver microsomes in the presence of NADPH, methiocarb sulfoxide, and a novel metabolite, methiocarb sulfone were detected. Methiocarb sulfoxide was oxidized to the sulfone by liver microsomes and reduced back to methiocarb by liver cytosol. Thus, the interconversion between methiocarb and the sulfoxide was found to be a new metabolic pathway for methiocarb by liver microsomes. The product of methiocarb hydrolysis, which is methylthio-3,5-xylenol (MX), was also oxidized to sulfoxide form by rat liver microsomes. The oxidations were catalyzed by human flavincontaining monooxygenase isoform (FMO1). CYP2C19, which is a human cytochrome P450 (CYP) isoform, catalyzed the sulfoxidations of methiocarb and MX, while CYP1A2 also exhibited oxidase activity toward MX. Methiocarb and carbaryl were not enzymatically hydrolyzed by the liver microsomes, but they were mainly hydrolyzed by plasma and albumin to MX and 1-naphthol, respectively. Both methiocarb and carbaryl exhibited PXR and PPARα agonistic activities; however, methiocarb sulfoxide and sulfone showed markedly reduced activities. In fact, when methiocarb was incubated with liver microsomes, the receptor activities were decreased. In contrast, MX and 1-naphthol showed nuclear receptor activities equivalent to those of their parent carbamates. Thus, the hydrolysis of methiocarb and carbaryl and the oxidation of methiocarb markedly modified their nuclear receptor activities.

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Section: Introductionsupporting

confidence: 68%

Metabolism of methiocarb and carbaryl by rat and human livers and plasma, and effect on their PXR, CAR and PPARα activities

et al. 2016

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“…Testosterone treatment results in a marked increase in kidney weight in castrated mice [38] and hypophysectomized male mice [39]. On the other hand, testosterone propionate decreases the weight of adrenal glands in castrated immature rats [30,32]. These prior reports clearly show that testosterone plays a role in relation to androgen-dependent organ weights.…”

mentioning

confidence: 75%

“…Concerning organ weight, there were no significant differences in the weights of reproductive organs (testis, seminal vesicle plus coagulating glands, levator ani muscle plus bulbocarvernosus muscle or glans penis, except for the prostate gland) between the KPtreated rats and the controls. Testosterone has been reported to play a role in increasing reproductive organ weights [29][30][31][32] in a dosedependent manner [23]. Dihydrotestosterone (DHT), a more potent androgen that is aromatized from testosterone, likewise stimulates the growth of accessory reproductive organs [33,34].…”

Section: Discussionmentioning

confidence: 99%

Oral Administration of Kaempferia parviflora did not Disturb Male Reproduction in Rats

et al. 2008

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Abstract.To investigate the androgenic effect of Kaempferia parviflora (KP), a Thai herbal plant, adult male rats were randomized into control and KP-treatment groups. Rats were treated orally with water in the control group and with 1,000 mg/kg/day of KP in the treatment group for 45 days. Blood samples were collected on days 10, 20, 30 and 45 for measurement of the serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, progesterone and corticosterone levels. The reproductive and non-reproductive organs were dissected on day 45 and weighed. Mating behavior was also observed on days 20 and 30. Body weight was measured throughout the study period. The results showed that KP induced an increase in body weight compared with the controls. There were no significant differences in the weights of either reproductive (testis, seminal vesicle plus coagulating gland, levator ani muscle plus bulbocarvernosus muscle and glans penis, except the prostate gland) or non-reproductive organs (kidney, adrenal gland and gastracnemius muscle). There were no significant differences in serum levels of either FSH or LH between the two groups. The serum testosterone and progesterone levels were insignificantly lower in the KP group during the first 30 days. The serum corticosterone levels in the KP group were lower than those in the controls throughout the study period and were significantly low on days 20 and 30. There were no significant changes in mating behavior in the rats treated with KP. Although KP affected the body weight and serum corticosterone level, it did not affect mating behavior, reproductive and non-reproductive organ weights or hormones related to the reproductive system in the adult male rats. Therefore, we conclude that the testosterone-like effect of KP did not disturb the hypothalamicpituitary-testicular axis or male reproduction. Key words: Body weight, Kaempferia parviflora, Luteinizing hormone (LH), Mating behavior, Testosterone (J. Reprod. Dev. 54: [375][376][377][378][379][380] 2008) aempferia parviflora Wall. Ex. Baker (KP), commonly referred to in Thai as Krachai Dum, is an indigenous herb that belongs to the Family Zingiberaceae. Nowadays, this plant is considered a Thai national herb. Based on studies using gas chromatographic techniques, many kinds of flavonoid substances, including 7,7,3,5,3,5,7,5,7,7, have been found in KP roots [1,2].KP root has been reported to have anti-gastric ulcer activity by preservation of gastric mucous secretion without inhibition of gastric acid secretion in male rats gavaged with an ether extract of KP [3]. In addition, daily administrations of KP at 20, 200, 1,000 or 2,000 mg/kg is not toxic to adult rats; however, 2,000 mg/kg seems to produce an increase in liver weight and decrease in eosinophil numbers (Chewapat et al. unpublished data).Native Thai people widely use this plant with alcohol or boiling water in traditional medicine to increase male libido and alleviative impotency because they believe this plant has androgenic activity altho...

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“…Serum was prepared as described previously [20]. All samples were measured in duplicate in the same assay.…”

Section: Hormone Analysismentioning

confidence: 99%

The Antiandrogenic Activity of the Fungicide N-(3, 5-Dichlorophenyl) Succinimide in In Vivo and In Vitro Assays

Zhang

Zheng

et al. 2007

Journal of Reproduction and Development

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Abstract. Antiandrogens can cause reproductive disorders in humans and wild animals. In the present study, we tested whether the fungicide N-(3, 5-dichlorophenyl) succinimide (NDPS) acts as an antiandrogen using in vitro and in vivo assays. A transient transfection system based on luciferase activity was utilized for in vitro analysis of the antiandrogeic activity of NDPS. Hershberger assay was used to analyze the antiandrogenic activity of NDPS in rats. The expressions of the androgenresponsive genes testosterone-repressed prostatic message-2 (TRPM-2) and prostate specific binding protein polypeptide C3 (PBP C3) in the rat ventral prostate were measured using real-time PCR. Our results indicated that NDPS can block 5-dehydrotestosterone (DHT)-induced androgen receptor (AR) activity in transiently transfected HepG2 cells (-5 log M). In the Hershberger assay, the weights of the seminal vesicles and levator ani/bulbocavernosus muscles were significantly decreased (P<0.05) in all NDPS groups, and the weights of the ventral prostate, dorsolateral prostate, and Cowper's glands were significantly decreased (P<0.05) in the 100 and 200 mg/kg NDPS groups. NDPS only decreased (P<0.05) the expression of PBP C3 and had no effect on the level of TRPM-2 (P>0.05). In conclusion, NDPS is a moderate antiandrogen that elicits antiandrogenic effects at least partly by antagonizing AR and increasing the expression of PBP C3.

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The combined antiandrogenic effects of five commonly used pesticides

Cited by 95 publications

References 28 publications

Metabolism of methiocarb and carbaryl by rat and human livers and plasma, and effect on their PXR, CAR and PPARα activities

Metabolism of methiocarb and carbaryl by rat and human livers and plasma, and effect on their PXR, CAR and PPARα activities

Oral Administration of Kaempferia parviflora did not Disturb Male Reproduction in Rats

The Antiandrogenic Activity of the Fungicide N-(3, 5-Dichlorophenyl) Succinimide in In Vivo and In Vitro Assays

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