Year: 2021
Type: dissertation
Abstract: Phytoecdysteroids have anabolic effects in humans and especially popular among athletes as sport performance enhancers.This study investigated the metabolism of an ecdysteroid, 20-Hydroxyecdysone (20HE), and its physiological effects, at concentrations not expected to be anabolic.The uPA (+/+)-SCID chimeric mice were administered 20HE.An excretion study was conducted on a male volunteer, after administration of low and high doses of supplement-derived 20HE.The effect of a 20HE containing supplement for two months was recorded in male athletes, with samples before and after consuming a 20HE supplement (n=4) or placebo (n=4).The detection of urinary 20HE was determined.Anthropometric changes were measured, as well as glucose, lipids and haematology, and an index of aerobic fitness (VO2 max).The hepatic transcriptome and proteome were analysed in RNA and protein extracted from the SCID mice treated with 20HE.Effects on Mitochondrial Membrane Potential (MMP) were tested in-vitro in human skeletal muscle cells and adipocytes treated with 20HE (5 and 10µM).Fifteen drug metabolizing genes were overexpressed, including NOS3, and, 29 were under expressed, including CYP17A1, in the 20HE treated group.In mice, following multiple doses, 20HE was detectable for up to 24h.In a human subject, following a high dose of supplement-derived 20HE, the ecdysteroid was first detected after 2 hours, with peak detection between 4-5 hours, and remained detectable for up to 48 hours.The lower concentration was only detectable for 36 hours.20HE supplement decreased diastolic blood pressure (p=0.05), with no significant changes in muscle mass and aerobic fitness.Seventy proteins were only detected in the 20HE group, while 37 genes were significantly differentially expressed.Upregulation of NOS3 was a consistent finding, and, validated at both the protein and RNA levels in human endothelial cells.Low dose, supplement-derived 20HE was detectable in human urine for at least 36 hours, and its administration (2 months) was not anabolic, but, was still able to alter systemic blood pressure and the expression of vasocrine genes (NOS3).Acknowledgement I want to start by giving my sincere gratitude and appreciation to my advisor Dr. Vidya Mohamed-Ali for not only allowing me to carry out a PhD but the unwavering and continuous support that she provided throughout my doctoral studies.Words do not do her justice for not only the help she offered but for her patience, motivation, and immensely vast knowledge she included as a complete package.Throughout my research and scribing this thesis, her guidance assisted and lifted me when I was at my nadir and kept me grounded when I was soaring as not to get over-confident.I couldn't imagine having a better advisor and mentor for my PhD studies and career.I need to extend my genuine appreciation to Prof. Mohammed Al-Maadheed, without his vision, support and encouragement this would not have been possible.It would be an unforgivable error on my part if I went without mentioning my supervisors: Dr David Morgan, and Dr Wael Kafineh.Their comments were both insightful encouraging.They also challenged me with their thought-provoking questions, which helped to widen my perspectives and thought processes.I am also thankful for my colleagues at the Anti-Doping Lab-Qatar for the stimulating discussions and continued support.I also acknowledge the support from the Qatar Computational Research Institute QCRI.Last but not least, I would like to thank my family: my mother, father and to my brother, sisters, husband and son for supporting and encouraging me spiritually
Author: Aljaber, Maneera
Language: English
Topic: Doping in Sports
Subfield: Sociology and Political Science
Field: Social Sciences
Domain: Social Sciences
Open Access status: green
OpenAlex ID: W7139743174