Metabolic studies with promagnon, methylclostebol and methasterone in the uPA+/+-SCID chimeric mice

Lootens, Leen; Meuleman, Philip; Leroux‐Roels, Geert; Eenoo, Peter Van

doi:10.1016/j.jsbmb.2011.06.010

Cited by 32 publications

(52 citation statements)

References 24 publications

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“…One approach which has the potential to address at least some of the inherent limitations of human in vitro biotransformation systems is to perform studies in vivo in "chimeric" mice with humanized livers, in which the majority of the hepatocyte population of the mouse liver has been replaced by human hepatocytes (Tateno et al 2004;Katoh and Yokoi, 2007;Okumura et al 2007;Inoue et al 2008;Inoue et al 2009;Strom et al 2010;Kamimura et al 2010;Chen et al 2011;De Serres et al 2011;Lootens et al 2011). These livers have been shown to express virtually the full complement of human Phase I and II metabolic enzymes and hepatic transporter proteins with gene-expression profiles and phenotypes similar (up to 85%) to those of the original donor liver (Tateno et al 2004;Yoshizato and Tateno, 2009;Strom et al 2010;Yamasaki et al 2010).…”

Section: Research Articlementioning

confidence: 99%

Evaluation of the pharmacokinetics, biotransformation and hepatic transporter effects of troglitazone in mice with humanized livers

Schulz-Utermoehl¹,

Sarda²,

Foster³

et al. 2011

Xenobiotica

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The pharmacokinetics, biotransformation and hepatic transporter effects of troglitazone were investigated following daily oral dosing, at 300 and 600 mg/kg, for 7 days to control (SCID) and chimeric (PXB) mice with humanized livers. Clinical chemistry revealed no consistent pattern of changes associated with troglitazone treatment in the PXB mouse. Human MRP2 but not mouse mrp2 was down-regulated following troglitazone treatment. Pharmacokinetic analysis revealed similar T(max) values for troglitazone in both mouse groups, a mono- and bi-phasic elimination phase in PXB and SCID mice, respectively, but a 3- to 5- and 2- to 5-fold higher C(max) and AUC, respectively, in PXB mice. Oxidative and conjugative metabolic pathways were identified, with the sulfate being the predominant metabolite in PXB compared to SCID mice (4- to 13-fold increase in liver and blood, respectively). The glucuronide conjugate was predominant in SCID mice. There was no evidence of glutathione conjugation. The primary oxidative pathways were mono- and di-oxidations which may also be attributed to quinone or hydroquinone derivatives. Several metabolites were observed in PXB mice only. As the troglitazone metabolic profiles in the PXB mouse were similar to reported human data the PXB mouse model can provide a useful first insight into circulating human metabolites of xenobiotics metabolized in the liver.

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Section: Research Articlementioning

confidence: 99%

Evaluation of the pharmacokinetics, biotransformation and hepatic transporter effects of troglitazone in mice with humanized livers

Schulz-Utermoehl¹,

Sarda²,

Foster³

et al. 2011

Xenobiotica

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“…Clostebol is a Schedule III controlled substance used medically in topical ophthalmologic and dermatologic treatments. A 17-alpha-alkylated version of clostebol (methylclostebol) was determined by chemical analysis to be present in significant amounts in a nutritional supplement (Lootens et al, 2011). We found methylclostebol to be a listed as an ingredient in four currently sold 'dietary supplements'.…”

Section: Methylclostebolmentioning

confidence: 99%

“…Mentabolan/Trestione Campbell et al (1963) and Segaloff (1963) • 7a-methyl-estra-4-en-3,17-dione 2010; Lootens et al, 2011). Designer steroids share a common mechanism of action with testosterone, acting at the androgen receptor (Diel et al, 2007;Kazlauskas, 2010).…”

Section: • Chemically Detected In Dietary Supplementsmentioning

confidence: 99%

“…2). Adding further to this complex regulatory issue, many products may be contaminated with a variety of unlabeled ingredients (Van Thuyne et al, 2006;Lootens et al, 2011). Multiple studies have exposed 'nutraceuticals' containing AAS not included on their product label (Baume et al, 2006;Van Thuyne et al, 2006;Lootens et al, 2011).…”

Section: Regulatory Obstaclesmentioning

confidence: 99%

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Designer steroids – over‐the‐counter supplements and their androgenic component: review of an increasing problem

2015

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SUMMARYColloquially referred to by various misleading monikers ('pro-hormones', 'natural steroids', 'testosterone boosters', etc.) designer anabolic steroids have been popular now for over a decade as a way to achieve classic anabolic steroid-like results from products sold in the legal marketplace. Recent evidence suggests that anabolic steroid use may be the most common cause of hypogonadism in men of reproductive age. Despite recent regulatory efforts that have banned specific compounds, many anabolic-androgenic steroids (AAS) remain available in over-the-counter dietary supplements that are legally sold in the United States. Severe side effects including hepatotoxicity, cholestasis, renal failure, hypogonadism, gynecomastia, and infertility have been reported secondary to the use of these products. While some of these side effects may be reversible, more aggressive use may result in more permanent end-organ damage as has been previously described for the case of aggressive AAS users (Rahnema et al., Fertil Steril, 2014). Designer AAS remain easily available for purchase in over-the-counter bodybuilding supplements and these products appear to be increasingly popular, despite the known health risks associated with their use. We conducted a systematic search to identify the designer steroids that are most commonly sold in dietary supplements as of April 2014 and review what is known regarding their potency and toxicity. We propose that the impact of AAS use on the reproductive and hormonal health of men is underestimated in the literature owing to previous studies' failure to account for designer steroid use. Lastly, we make clinical recommendations to help physicians steer patients away from potentially harmful supplements, and summarize key regulatory obstacles that have allowed potent androgens to remain unregulated in the legal marketplace.

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“…6 β -Chloro-androst-4-en-17 β-ol-3-one (22) is an epimer of hexadrone, and has milder properties than hexadrone. 3-Chloro-17-methylandrostenediol (promagnon, 23) is a methylated derivative of the anabolic steroid testosterone, which is designed to stimulate and build muscle mass, as well as improve muscle density, vascularity and hardness (Lootens et al, 2011). Additional biological activity for anabolic chlorinated hormones (17-23) is shown in Table 2.…”

Section: Chlorinated Steroidsmentioning

confidence: 99%

Halogenated (F, Cl, Br, I) Anabolic Steroids and their Biological Activities

Kilimnik¹,

Gloriozova²,

Dembitsky³

2017

Int. J. Curr. Res. Biosci. Plant Biol.

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A b s t r a c t A r t i c l e I n f oThe present review describes the biological activities of synthetic anabolic halogenated (F, Cl, Br and I) steroids. About sixty biologically active halogenated steroids have shown confirmed anti-inflammatory, estrogenic, anabolic, gynecological disorders, anti-arthritic, antineoplastic, and other activities. The structures and reported and predicted activities of halogenated steroids are available. With the computer programme PASS and based on structure-activity relationships (SAR), some additional activities are also predicted, which point towards new possible applications of these lipids. This review emphasizes the role of halogenated steroids as an important source and potential leads for drug discovery and they are of great interest to chemists, physicians, biologists, pharmacologists and the pharmaceutical industry.

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Metabolic studies with promagnon, methylclostebol and methasterone in the uPA+/+-SCID chimeric mice

Cited by 32 publications

References 24 publications

Evaluation of the pharmacokinetics, biotransformation and hepatic transporter effects of troglitazone in mice with humanized livers

Evaluation of the pharmacokinetics, biotransformation and hepatic transporter effects of troglitazone in mice with humanized livers

Designer steroids – over‐the‐counter supplements and their androgenic component: review of an increasing problem

Halogenated (F, Cl, Br, I) Anabolic Steroids and their Biological Activities

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