Physiological linkage of gender, bioavailable hydroxytyrosol derivatives, and their metabolites with systemic catecholamine metabolism

2017 ◽  
Vol 8 (12) ◽  
pp. 4570-4581 ◽  
Author(s):  
R. Domínguez-Perles ◽  
D. Auñón ◽  
F. Ferreres ◽  
A. Gil-Izquierdo

Unraveling the physiological linkage between gender, bioavailable hydroxytyrosol derivatives, and their microbial metabolites and the systemic metabolism of catecholamines.

Author(s):  
Н.В. Белобородова ◽  
В.В. Мороз ◽  
А.Ю. Бедова

Интеграция метаболизма макроорганизма и его микробиоты, обеспечивающая в норме симбиоз и саногенез, нарушается при заболеваниях, травме, критическом состоянии, и вектор взаимодействия может изменяться в пользу прокариотов по принципу «метаболиты бактерий - против хозяина». Анализ литературы показал, что, с одной стороны, имеется живой интерес к ароматическим микробным метаболитам, с другой - отсутствует четкое представление об их роли в организме человека. Публикации, касающиеся ряда ароматических микробных метаболитов (фенилкарбоновых кислот, ФКК), как правило, не связаны между собой по тематике и направлены на решение тех или иных прикладных задач в разных областях биологии и медицины. Цель обзора - анализ информации о происхождении, биологических эффектах ФКК в экспериментах in vitro и in vivo , и клинических наблюдениях. Обобщая результаты приведенных в обзоре исследований на клеточном, субклеточном и молекулярном уровнях, логично предположить участие ароматических микробных метаболитов в патогенезе полиорганной недостаточности при сепсисе. Наиболее перспективным для раскрытия роли ароматических микробных метаболитов представляется изучение механизмов вторичной почечной недостаточности и септической энцефалопатии. Важным направлением для будущих исследований является изучение влияния продуктов микробной биодеградации ароматических соединений на развитие диссеминированного внутрисосудистого свертывания крови, артериальной гипотензии и септического шока. Результаты дальнейших исследований будут иметь не только фундаментальное значение, но и обогатят практическую медицину новыми диагностическими и лечебными технологиями. Significant increases in blood concentrations of some aromatic metabolites (phenylcarboxylic acids, PhCAs) in patients with sepsis have been previously shown. Enhanced bacterial biodegradation of aromatic compounds has been demonstrated to considerably contribute to this process. Integration of macroorganism metabolism and its microbiota, which provides normal symbiosis and sanogenesis, is disturbed in diseases, trauma, and critical conditions. Direction of this interaction may change in favor of prokaryotes according to the principle, “bacterial metabolites are against the host”. Analysis of literature showed a particular interest of many investigators to aromatic microbial metabolites. However, there is no clear understanding of their role in the human body. Publications on PhCAs are generally not thematically interrelated and usually focus on solving applied tasks in different fields of biology and medicine. The aim of this work was to consolidate existing information about origin and biological effects of PhCAs in in vitro / in vivo experiments and some clinical findings. The presented summary of reported data from studies performed at cellular, sub-cellular, and molecular levels suggests participation of aromatic microbial metabolites in the pathogenesis of multiple organ failure in sepsis. Studying mechanisms of secondary renal failure and septic encephalopathy is most promising for discovering the function of aromatic microbial metabolites. Effects of microbial biodegradation products of aromatic substances on development of disseminated intravascular coagulation, hypotension, and septic shock are an important challenge for future studies. Results of further investigations will be not only fundamental, but will also enrich medical practice with new diagnostic and therapeutic technologies.


Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 159
Author(s):  
Yao Peng ◽  
Yuqiang Nie ◽  
Jun Yu ◽  
Chi Chun Wong

Colorectal cancer (CRC) is one of the leading cancers that cause cancer-related deaths worldwide. The gut microbiota has been proved to show relevance with colorectal tumorigenesis through microbial metabolites. By decomposing various dietary residues in the intestinal tract, gut microbiota harvest energy and produce a variety of metabolites to affect the host physiology. However, some of these metabolites are oncogenic factors for CRC. With the advent of metabolomics technology, studies profiling microbiota-derived metabolites have greatly accelerated the progress in our understanding of the host-microbiota metabolism interactions in CRC. In this review, we briefly summarize the present metabolomics techniques in microbial metabolites researches and the mechanisms of microbial metabolites in CRC pathogenesis, furthermore, we discuss the potential clinical applications of microbial metabolites in cancer diagnosis and treatment.


2021 ◽  
pp. 2100380
Author(s):  
Valentina Cecarini ◽  
Massimiliano Cuccioloni ◽  
Yadong Zheng ◽  
Laura Bonfili ◽  
Chunmei Gong ◽  
...  

2021 ◽  
Vol 22 (11) ◽  
pp. 5999
Author(s):  
David S. Goldstein

3,4-Dihydroxyphenylacetaldehyde (DOPAL) is the focus of the catecholaldehyde hypothesis for the pathogenesis of Parkinson’s disease and other Lewy body diseases. The catecholaldehyde is produced via oxidative deamination catalyzed by monoamine oxidase (MAO) acting on cytoplasmic dopamine. DOPAL is autotoxic, in that it can harm the same cells in which it is produced. Normally, DOPAL is detoxified by aldehyde dehydrogenase (ALDH)-mediated conversion to 3,4-dihydroxyphenylacetic acid (DOPAC), which rapidly exits the neurons. Genetic, environmental, or drug-induced manipulations of ALDH that build up DOPAL promote catecholaminergic neurodegeneration. A concept derived from the catecholaldehyde hypothesis imputes deleterious interactions between DOPAL and the protein alpha-synuclein (αS), a major component of Lewy bodies. DOPAL potently oligomerizes αS, and αS oligomers impede vesicular and mitochondrial functions, shifting the fate of cytoplasmic dopamine toward the MAO-catalyzed formation of DOPAL—destabilizing vicious cycles. Direct and indirect effects of DOPAL and of DOPAL-induced misfolded proteins could “freeze” intraneuronal reactions, plasticity of which is required for neuronal homeostasis. The extent to which DOPAL toxicity is mediated by interactions with αS, and vice versa, is poorly understood. Because of numerous secondary effects such as augmented spontaneous oxidation of dopamine by MAO inhibition, there has been insufficient testing of the catecholaldehyde hypothesis in animal models. The clinical pathophysiological significance of genetics, emotional stress, environmental agents, and interactions with numerous proteins relevant to the catecholaldehyde hypothesis are matters for future research. The imposing complexity of intraneuronal catecholamine metabolism seems to require a computational modeling approach to elucidate clinical pathogenetic mechanisms and devise pathophysiology-based, individualized treatments.


2021 ◽  
pp. 114220
Author(s):  
Marta Vigier ◽  
Katherine R. Thorson ◽  
Elisabeth Andritsch ◽  
Herbert Stoeger ◽  
Leonie Suerth ◽  
...  

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