Annual banned‐substance review – Analytical approaches in human sports drug testing

Thevis, Mario; Kuuranne, Tiia; Geyer, Hans

doi:10.1002/dta.2735

Cited by 44 publications

(35 citation statements)

References 127 publications

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“…Recent developments in anti-doping science include a growing emphasis on the analysis of steroid sulfate metabolites. The analysis of steroid sulfates has been shown to increase the detection times for a range of steroid agents [2][3][4][5][6][7][8] and can also be used to distinguish between endogenous steroids and otherwise identical exogenously administered steroids of synthetic origin. 4,[9][10][11][12][13] Although the direct detection of steroid sulfates can be readily achieved using liquid chromatographymass spectrometry in combination with electrospray ionisation, 14 many analytical approaches are hampered due to the lack of suitable enzymatic or chemical methods for sulfate ester hydrolysis prior to analysis.…”

Section: Introductionmentioning

confidence: 99%

Enhancing the Steroid Sulfatase Activity of the Arylsulfatase from Pseudomonas aeruginosa

et al. 2018

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Steroidal sulfate esters play a central role in many physiological processes. They serve as the reservoir for endogenous sex hormones and form a significant fraction of the steroid metabolite pool. The analysis of steroid sulfates is thus essential in fields such as medical science and sports drug testing. Although the direct detection of steroid sulfates can be readily achieved using liquid chromatographymass spectrometry, many analytical approaches, including gas chromatography-mass spectrometry, are hampered due to the lack of suitable enzymatic or chemical methods for sulfate ester hydrolysis prior to analysis. Enhanced methods of steroid sulfate hydrolysis would expand analytical possibilities for the study of these widely occurring metabolites. The arylsulfatase from Pseudomonas aeruginosa (PaS) is a purified enzyme capable of hydrolysing steroid sulfates. However, this enzyme requires improvement to hydrolytic activity and substrate scope in order to be useful in analytical applications. These improvements were sought by applying semi-rational design to mutate amino acid residues neighbouring the enzyme active site. Mutagenesis was implemented on both single and multiple residue sites. Screening by UPLC-MS was performed to test the steroid sulfate hydrolysis activity of these mutant libraries against testosterone sulfate. This approach revealed the steroid sulfate binding pocket and resulted in three mutants that showed an improvement in catalytic efficiency (Vmax/KM) of more than 150 times that of wild-type PaS. The substrate scope of PaS was expanded and a modest increase in thermostability was observed. Finally, molecular dynamics simulations of enzymesubstrate complexes were used to provide qualitative insight into the structural origin of the observed effects.

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Section: Introductionmentioning

confidence: 99%

Enhancing the Steroid Sulfatase Activity of the Arylsulfatase from Pseudomonas aeruginosa

et al. 2018

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“…A more comprehensive understanding of the effects of hormones due to relative energy deficits associated with exercise is necessary to better appreciate this physiological relationship and to take effective action improving health and athletic performance. Also, peptide hormones, including GH, IGF-1, and ghrelin, are registered as banned substances by the international anti-doping agency of professional sports [57]. However, the blood levels of these hormones change constantly due to multiple physiological stresses including exercise.…”

Section: Regulation Of Energy Metabolism By Peptide Hormones In Relatmentioning

confidence: 99%

A new action of peptide hormones for survival in a low-nutrient environment

et al. 2019

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Malnutrition occurs when nutrient intake is too low for any reason and occurs regardless of gender or age. Therefore, besides loss of eating or digestive functionality due to illness, malnutrition can occur when a healthy individual undergoes an extreme diet and biases their nutrition, or when athletes exerts more energy than they can replenish through food. It has recently been reported that in Japan, the mortality rate of leaner individuals is equal to or higher than that of obese people. It is important to understand what homeostatic maintenance mechanism is behind this when the body is under hypotrophic conditions. Such mechanisms are generally endocranially controlled. We address this fundamental concern in this paper by focusing on peptide hormones. We introduce a mechanism for survival in a malnourished state via the regulation of food intake and temperature. Additionally, we will discuss the latest findings and future prospects for research on changes in the endocrine environment associated with malnutrition associated with exercise. We also review changes in next-generation endocrine environments when caused by malnutrition brought on by dieting.

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“…It turns out that some of the dietary supplements and herbal products contain AAS without an indication on the etiquettes, which leads to an unintentional intake [8][9][10][11]13]. Moreover, multiple athletes take AAS in different forms together with other substances to increase effectiveness or diminish the side effects, which leads to polypragmasie [5,8,12,[39][40][41]44]. This review aims to demonstrate the AAS induced hepatotoxicity, it is based on the medical literature from the last 10 years.…”

Section: Introduction and Purposementioning

confidence: 99%

Hepatotoxicity of anabolic androgenic steroids in sport

Sekuła¹,

Świerczyńska²,

Smoluchowski³

et al. 2020

J Educ Health Sport

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Introduction and purpose: Anabolic-androgenic steroids (AAS) abuse is a common practice among professional as well as recreational athletes. The prevalence of this phenomenon seems to be continuously escalating, too. Even though AAS abuse may provide a desirable haematopoietic and musculotrophic effect, it causes a wide variety of local and systemic side effects. This review aims to demonstrate the AAS induced hepatotoxicity, it is based on the medical literature from the last 10 years. Brief description of the state of knowledge: Orally administered 17-α-alkylated steroids are considered to be the most hepatotoxic. They increase the number of reactive oxygen species (ROS) which directly injure the liver tissue. It may be manifested as an elevation of liver enzymes, peliosis hepatis or distinctive acute cholestasis. Furthermore, ASS abuse for a prolonged period of time may induce the growth of hepatocellular adenoma and hepatocellular cancer. Moreover, AAS intake can lead to liver enlargement, development of toxicant-associated fatty liver disease (TAFLD) and increase the risk of HCV and HBV infection. Conclusions: The collaboration of scientists, doctors, sports associations and governments is substantial. Introduction of innovative AAS detection methods and enforcement of stricter anti-doping law may contribute to prevention of health consequences resulting from AAS abuse among athletes.

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Annual banned‐substance review – Analytical approaches in human sports drug testing

Cited by 44 publications

References 127 publications

Enhancing the Steroid Sulfatase Activity of the Arylsulfatase from Pseudomonas aeruginosa

Enhancing the Steroid Sulfatase Activity of the Arylsulfatase from Pseudomonas aeruginosa

A new action of peptide hormones for survival in a low-nutrient environment

Hepatotoxicity of anabolic androgenic steroids in sport

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