Efficacy of Thymoquinone and Hesperidin in Attenuating Cardiotoxicity from 5-Fluorouracil: Insights from In Vivo and In Silico Studies

5-Fluorouracil (5-FU) is widely used in chemotherapy but poses serious risks of cardiotoxicity, which can significantly affect treatment outcomes. Identifying interventions that can prevent these adverse effects without undermining anticancer efficacy is crucial. This study investigates the efficacy...

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Main Authors: Juveriya Farooq, Rokeya Sultana, Jainey P. James, Zakiya Fathima C, Ali F. Almutairy, Abubakar Siddique Mustafa Hussain
Format: Article
Language:English
Published: MDPI AG 2024-09-01
Series:Toxics
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Online Access:https://www.mdpi.com/2305-6304/12/9/688
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author Juveriya Farooq
Rokeya Sultana
Jainey P. James
Zakiya Fathima C
Ali F. Almutairy
Abubakar Siddique Mustafa Hussain
author_facet Juveriya Farooq
Rokeya Sultana
Jainey P. James
Zakiya Fathima C
Ali F. Almutairy
Abubakar Siddique Mustafa Hussain
author_sort Juveriya Farooq
collection DOAJ
description 5-Fluorouracil (5-FU) is widely used in chemotherapy but poses serious risks of cardiotoxicity, which can significantly affect treatment outcomes. Identifying interventions that can prevent these adverse effects without undermining anticancer efficacy is crucial. This study investigates the efficacy of Thymoquinone (TQ) and Hesperidin (HESP) in preventing cardiotoxicity induced by 5-FU in Wistar rats and elucidates the molecular interactions through docking studies. We employed an experimental design involving multiple groups of Wistar rats exposed to 5-FU, with and without the concurrent administration of TQ and HESP. Cardiac function markers, oxidative stress indicators, and inflammatory markers were assessed. Additionally, molecular docking was used to analyze the interaction of TQ and HESP with key inflammatory proteins. Treatment with TQ and HESP not only lowered levels of cardiac enzymes but also improved antioxidant capacity and reduced inflammation in cardiac tissues. Notably, the combination of TQ and HESP provided more significant protective effects than either agent alone. Molecular docking supported these findings, showing effective binding of TQ and HESP to inflammatory targets. TQ and HESP demonstrate potential as protective agents against cardiotoxicity in 5-FU-treated rats, with their combined use offering enhanced protection. These findings suggest a viable strategy for reducing cardiac risks associated with 5-FU chemotherapy.
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spelling doaj-art-c1d29a4e73e54bd7be4813a8733e1cb72025-08-20T01:55:53ZengMDPI AGToxics2305-63042024-09-0112968810.3390/toxics12090688Efficacy of Thymoquinone and Hesperidin in Attenuating Cardiotoxicity from 5-Fluorouracil: Insights from In Vivo and In Silico StudiesJuveriya Farooq0Rokeya Sultana1Jainey P. James2Zakiya Fathima C3Ali F. Almutairy4Abubakar Siddique Mustafa Hussain5Department of Pharmacology, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, IndiaDepartment of Pharmacognosy, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, IndiaDepartment of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Mangalore 575018, IndiaDepartment of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Mangalore 575018, IndiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi ArabiaDiscipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor 11700, Malaysia5-Fluorouracil (5-FU) is widely used in chemotherapy but poses serious risks of cardiotoxicity, which can significantly affect treatment outcomes. Identifying interventions that can prevent these adverse effects without undermining anticancer efficacy is crucial. This study investigates the efficacy of Thymoquinone (TQ) and Hesperidin (HESP) in preventing cardiotoxicity induced by 5-FU in Wistar rats and elucidates the molecular interactions through docking studies. We employed an experimental design involving multiple groups of Wistar rats exposed to 5-FU, with and without the concurrent administration of TQ and HESP. Cardiac function markers, oxidative stress indicators, and inflammatory markers were assessed. Additionally, molecular docking was used to analyze the interaction of TQ and HESP with key inflammatory proteins. Treatment with TQ and HESP not only lowered levels of cardiac enzymes but also improved antioxidant capacity and reduced inflammation in cardiac tissues. Notably, the combination of TQ and HESP provided more significant protective effects than either agent alone. Molecular docking supported these findings, showing effective binding of TQ and HESP to inflammatory targets. TQ and HESP demonstrate potential as protective agents against cardiotoxicity in 5-FU-treated rats, with their combined use offering enhanced protection. These findings suggest a viable strategy for reducing cardiac risks associated with 5-FU chemotherapy.https://www.mdpi.com/2305-6304/12/9/6885-Fluorouracilcardiotoxicitythymoquinonehesperidinmolecular docking
spellingShingle Juveriya Farooq
Rokeya Sultana
Jainey P. James
Zakiya Fathima C
Ali F. Almutairy
Abubakar Siddique Mustafa Hussain
Efficacy of Thymoquinone and Hesperidin in Attenuating Cardiotoxicity from 5-Fluorouracil: Insights from In Vivo and In Silico Studies
Toxics
5-Fluorouracil
cardiotoxicity
thymoquinone
hesperidin
molecular docking
title Efficacy of Thymoquinone and Hesperidin in Attenuating Cardiotoxicity from 5-Fluorouracil: Insights from In Vivo and In Silico Studies
title_full Efficacy of Thymoquinone and Hesperidin in Attenuating Cardiotoxicity from 5-Fluorouracil: Insights from In Vivo and In Silico Studies
title_fullStr Efficacy of Thymoquinone and Hesperidin in Attenuating Cardiotoxicity from 5-Fluorouracil: Insights from In Vivo and In Silico Studies
title_full_unstemmed Efficacy of Thymoquinone and Hesperidin in Attenuating Cardiotoxicity from 5-Fluorouracil: Insights from In Vivo and In Silico Studies
title_short Efficacy of Thymoquinone and Hesperidin in Attenuating Cardiotoxicity from 5-Fluorouracil: Insights from In Vivo and In Silico Studies
title_sort efficacy of thymoquinone and hesperidin in attenuating cardiotoxicity from 5 fluorouracil insights from in vivo and in silico studies
topic 5-Fluorouracil
cardiotoxicity
thymoquinone
hesperidin
molecular docking
url https://www.mdpi.com/2305-6304/12/9/688
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