Toxicological impact of three pharmacological therapeutics on human sperm

Detalhes bibliográficos
Autor(a) principal: Garcia, Carolina Capucha
Data de Publicação: 2021
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10773/33615
Resumo: Therapeutic drugs can negatively affect male fertility by inducing toxic effects that impair sperm production and/or function. Some drugs are able to cross the blood-testis barrier (BTB) and act directly on germ cells, interfering with sperm function. With the world pandemic of COVID-19, several drugs were repurposed as treatment options. As a result, these drugs started to be extensively administered worldwide. The urge for full knowledge on drugs’ safety became even more evident, to avoid undesirable side effects. Therefore, the aim of this in vitro study was to evaluate the toxicological effects of three therapeutic drugs used in COVID-19, in human sperm cells. Hydroxychloroquine (HCQ; antimalarial), dexamethasone (DEX; glucocorticoid) and remdesivir (RDV; antiviral) were the drugs studied. DEX and RDV are also recommend in co-administration for some COVID-19 patients, thus, these two drugs were evaluated for individual combined effects. Sperm vitality and motility, sperm oxidative stress and DNA damages were assessed in sperm cells exposed to usual therapeutic regimen of each drug and compared to a control group. HCQ was the only drug to induce significant effects in sperm vitality and motility. All drugs induced sperm DNA fragmentation, without alter the oxidative stress levels. Therefore, this study suggests HCQ is the most toxic drug for sperm cells, and that sperm DNA fragmentation is induced by different mechanism rather than exclusively due to oxidative stress. Moreover, results outlined the importance to include sperm DNA fragmentation evaluation in routine sperm analysis at fertility clinics. DEX and RDV seem to have addictive effects when administered simultaneously, however, further investigation is required to confirm these effects.
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spelling Toxicological impact of three pharmacological therapeutics on human spermHydroxychloroquineDexamethasoneRemdesivirDrug in vitro toxicityHuman spermSperm DNA fragmentationSperm vitalitySperm motilitySperm oxidative stressTherapeutic drugs can negatively affect male fertility by inducing toxic effects that impair sperm production and/or function. Some drugs are able to cross the blood-testis barrier (BTB) and act directly on germ cells, interfering with sperm function. With the world pandemic of COVID-19, several drugs were repurposed as treatment options. As a result, these drugs started to be extensively administered worldwide. The urge for full knowledge on drugs’ safety became even more evident, to avoid undesirable side effects. Therefore, the aim of this in vitro study was to evaluate the toxicological effects of three therapeutic drugs used in COVID-19, in human sperm cells. Hydroxychloroquine (HCQ; antimalarial), dexamethasone (DEX; glucocorticoid) and remdesivir (RDV; antiviral) were the drugs studied. DEX and RDV are also recommend in co-administration for some COVID-19 patients, thus, these two drugs were evaluated for individual combined effects. Sperm vitality and motility, sperm oxidative stress and DNA damages were assessed in sperm cells exposed to usual therapeutic regimen of each drug and compared to a control group. HCQ was the only drug to induce significant effects in sperm vitality and motility. All drugs induced sperm DNA fragmentation, without alter the oxidative stress levels. Therefore, this study suggests HCQ is the most toxic drug for sperm cells, and that sperm DNA fragmentation is induced by different mechanism rather than exclusively due to oxidative stress. Moreover, results outlined the importance to include sperm DNA fragmentation evaluation in routine sperm analysis at fertility clinics. DEX and RDV seem to have addictive effects when administered simultaneously, however, further investigation is required to confirm these effects.A fertilidade masculina pode ser negativamente afetada por diversos fármacos, que induzem efeitos tóxicos no sistema reprodutor masculino, resultando em profundas alterações na formação e/ou função dos espermatozoides. Alguns fármacos são capazes de atravessar a barreira hemato-testicular e atuar diretamente nas células germinativas podendo vir a interferir com a capacidade de fertilização dos espermatozoides. A pandemia COVID-19 obrigou à mobilização de diversos recursos farmacológicos. Inúmeros fármacos foram repropostos como tratamento para a COVID-19, passando a ser amplamente administrados em todo o mundo, tornando-se ainda mais urgente o total conhecimento da segurança dos fármacos em questão. Assim sendo, foi desenhado este estudo in vitro, para avaliar os efeitos de três fármacos utilizados como terapia para pacientes COVID-19 nos espermatozoides humanos. Hidroxicloroquina (HCQ; antimalárico), dexametasona (DEX, glucocorticoide) e remdesivir (RDV; antiviral) foram os fármacos estudados, sendo que a DEX e o RDV foram testados individualmente e em combinação. Os espermatozoides foram expostos às concentrações terapêuticas dos fármacos e os seguintes parâmetros foram avaliados: vitalidade, motilidade, stress oxidativo e danos no DNA. De acordo com os resultados, apenas a HCQ diminuiu significativamente a vitalidade e motilidade dos espermatozoides. Todos os fármacos induziram fragmentação no DNA espérmico, ainda que sem alterar os níveis de stress oxidativo. Assim, concluiu-se que a HCQ é o fármaco com maior potencial tóxico para os espermatozoides, induzindo danos ao nível macro e microscópico, e que a fragmentação do DNA é induzida por mecanismos que não implicam unicamente produção de espécies reativas de oxigénio. Mais ainda, este estudo tornou evidente a necessidade de incluir uma análise ao DNA espérmico nos espermogramas realizados em clinicas de fertilidade. DEX e RDV parecem ter um efeito aditivo quando administrados em conjunto, no entanto é necessário um estudo mais aprofundado para confirmar os seus efeitos em concomitância.2022-04-05T10:30:19Z2021-12-09T00:00:00Z2021-12-09info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/33615engGarcia, Carolina Capuchainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T12:04:41Zoai:ria.ua.pt:10773/33615Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:05:00.634848Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Toxicological impact of three pharmacological therapeutics on human sperm
title Toxicological impact of three pharmacological therapeutics on human sperm
spellingShingle Toxicological impact of three pharmacological therapeutics on human sperm
Garcia, Carolina Capucha
Hydroxychloroquine
Dexamethasone
Remdesivir
Drug in vitro toxicity
Human sperm
Sperm DNA fragmentation
Sperm vitality
Sperm motility
Sperm oxidative stress
title_short Toxicological impact of three pharmacological therapeutics on human sperm
title_full Toxicological impact of three pharmacological therapeutics on human sperm
title_fullStr Toxicological impact of three pharmacological therapeutics on human sperm
title_full_unstemmed Toxicological impact of three pharmacological therapeutics on human sperm
title_sort Toxicological impact of three pharmacological therapeutics on human sperm
author Garcia, Carolina Capucha
author_facet Garcia, Carolina Capucha
author_role author
dc.contributor.author.fl_str_mv Garcia, Carolina Capucha
dc.subject.por.fl_str_mv Hydroxychloroquine
Dexamethasone
Remdesivir
Drug in vitro toxicity
Human sperm
Sperm DNA fragmentation
Sperm vitality
Sperm motility
Sperm oxidative stress
topic Hydroxychloroquine
Dexamethasone
Remdesivir
Drug in vitro toxicity
Human sperm
Sperm DNA fragmentation
Sperm vitality
Sperm motility
Sperm oxidative stress
description Therapeutic drugs can negatively affect male fertility by inducing toxic effects that impair sperm production and/or function. Some drugs are able to cross the blood-testis barrier (BTB) and act directly on germ cells, interfering with sperm function. With the world pandemic of COVID-19, several drugs were repurposed as treatment options. As a result, these drugs started to be extensively administered worldwide. The urge for full knowledge on drugs’ safety became even more evident, to avoid undesirable side effects. Therefore, the aim of this in vitro study was to evaluate the toxicological effects of three therapeutic drugs used in COVID-19, in human sperm cells. Hydroxychloroquine (HCQ; antimalarial), dexamethasone (DEX; glucocorticoid) and remdesivir (RDV; antiviral) were the drugs studied. DEX and RDV are also recommend in co-administration for some COVID-19 patients, thus, these two drugs were evaluated for individual combined effects. Sperm vitality and motility, sperm oxidative stress and DNA damages were assessed in sperm cells exposed to usual therapeutic regimen of each drug and compared to a control group. HCQ was the only drug to induce significant effects in sperm vitality and motility. All drugs induced sperm DNA fragmentation, without alter the oxidative stress levels. Therefore, this study suggests HCQ is the most toxic drug for sperm cells, and that sperm DNA fragmentation is induced by different mechanism rather than exclusively due to oxidative stress. Moreover, results outlined the importance to include sperm DNA fragmentation evaluation in routine sperm analysis at fertility clinics. DEX and RDV seem to have addictive effects when administered simultaneously, however, further investigation is required to confirm these effects.
publishDate 2021
dc.date.none.fl_str_mv 2021-12-09T00:00:00Z
2021-12-09
2022-04-05T10:30:19Z
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instacron:RCAAP
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