Repurposing Disulfiram as an Anti-Obesity Drug: Treating and Preventing Obesity in High-Fat-Fed Rats

Ziad Omran,1 Ryan Sheikh,2 Othman A Baothman,2 Mazin A Zamzami,2 Mohamed Alarjah1 1College of Pharmacy, Umm Al-Qura University, Makkah 21955, Kingdom of Saudi Arabia; 2Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Kingdom of Saudi ArabiaCorrespondence: Ziad OmranCol...

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Autores principales:	Omran Z, Sheikh R, Baothman OA, Zamzami MA, Alarjah M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	obesity drug repurposing aldh1a1 disulfiram Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/e355f663a6c1417dbd0e7b4dc185fd39
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spelling	oai:doaj.org-article:e355f663a6c1417dbd0e7b4dc185fd392021-12-02T09:22:57ZRepurposing Disulfiram as an Anti-Obesity Drug: Treating and Preventing Obesity in High-Fat-Fed Rats1178-7007https://doaj.org/article/e355f663a6c1417dbd0e7b4dc185fd392020-05-01T00:00:00Zhttps://www.dovepress.com/repurposing-disulfiram-as-an-anti-obesity-drug-treating-and-preventing-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Ziad Omran,1 Ryan Sheikh,2 Othman A Baothman,2 Mazin A Zamzami,2 Mohamed Alarjah1 1College of Pharmacy, Umm Al-Qura University, Makkah 21955, Kingdom of Saudi Arabia; 2Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Kingdom of Saudi ArabiaCorrespondence: Ziad OmranCollege of Pharmacy, Umm Al-Qura University, Al-Abidiyya, Makkah 21955, Kingdom of Saudi ArabiaTel +966 5 46461441Email zhomran@uqu.edu.saBackground and Objectives: A drug repurposing strategy is an approach for identifying new therapeutic uses for approved or investigational drugs. Thanks to the moderate cost of repurposing a drug compared to bringing new chemical entity to the market, drug repurposing is rapidly gaining ground. The aim of this work is to study the anti-obesity effect of disulfiram (DSF), an irreversible aldehyde dehydrogenase inhibitor approved by the Food and Drug Administration (FDA) to treat chronic alcoholism since 1951.Methods: Thirty male Albino rats were randomly assigned to six groups. G1, the control group, was given a standard diet. G2, the positive control group, was given a high-fat diet (HFD). G3 was given an HFD, and DSF 50 mg/kg/day was administered orally from day one for six weeks. G4 was given an HFD, and DSF 200 mg/kg/day was administered orally from day one for six weeks. G5 was given an HFD for six weeks; then treatment started with 50 mg/kg/day DSF orally. G6 was given an HFD for six weeks; then treatment started with 200 mg/kg/day DSF orally for three weeks. The body weight, food consumption and blood glucose levels were monitored over the given time interval.Results: Both doses of DSF significantly limited the body weight gain caused by an HFD for the treated animals. HF-fed rats received 50 and 200 mg/kg/day of DSF had their body weight increased by 51.93 ± 7.89% and 20.88 ± 15.05% respectively, whereas the body weight of control animals increased by 93.1 ± 20.04%. DSF also significantly decreased the body weight of obese animals. At 50 and 200 mg/kg/day of DSF, HF-fed rats lost 16.74 ± 8.61% and 23.9 ± 3.93% respectively, as their untreated counterparts had their body weight increased by 11.85 ± 3.79% after three weeks of treatment, thus restoring a body weight matching those who received a standard diet.Conclusion: FDA-approved disulfiram has a strong anti-obesity effect on HFD-fed rats.Keywords: obesity, drug repurposing, Aldh1a1, disulfiramOmran ZSheikh RBaothman OAZamzami MAAlarjah MDove Medical Pressarticleobesitydrug repurposingaldh1a1disulfiramSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 1473-1480 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	obesity drug repurposing aldh1a1 disulfiram Specialties of internal medicine RC581-951
spellingShingle	obesity drug repurposing aldh1a1 disulfiram Specialties of internal medicine RC581-951 Omran Z Sheikh R Baothman OA Zamzami MA Alarjah M Repurposing Disulfiram as an Anti-Obesity Drug: Treating and Preventing Obesity in High-Fat-Fed Rats
description	Ziad Omran,1 Ryan Sheikh,2 Othman A Baothman,2 Mazin A Zamzami,2 Mohamed Alarjah1 1College of Pharmacy, Umm Al-Qura University, Makkah 21955, Kingdom of Saudi Arabia; 2Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Kingdom of Saudi ArabiaCorrespondence: Ziad OmranCollege of Pharmacy, Umm Al-Qura University, Al-Abidiyya, Makkah 21955, Kingdom of Saudi ArabiaTel +966 5 46461441Email zhomran@uqu.edu.saBackground and Objectives: A drug repurposing strategy is an approach for identifying new therapeutic uses for approved or investigational drugs. Thanks to the moderate cost of repurposing a drug compared to bringing new chemical entity to the market, drug repurposing is rapidly gaining ground. The aim of this work is to study the anti-obesity effect of disulfiram (DSF), an irreversible aldehyde dehydrogenase inhibitor approved by the Food and Drug Administration (FDA) to treat chronic alcoholism since 1951.Methods: Thirty male Albino rats were randomly assigned to six groups. G1, the control group, was given a standard diet. G2, the positive control group, was given a high-fat diet (HFD). G3 was given an HFD, and DSF 50 mg/kg/day was administered orally from day one for six weeks. G4 was given an HFD, and DSF 200 mg/kg/day was administered orally from day one for six weeks. G5 was given an HFD for six weeks; then treatment started with 50 mg/kg/day DSF orally. G6 was given an HFD for six weeks; then treatment started with 200 mg/kg/day DSF orally for three weeks. The body weight, food consumption and blood glucose levels were monitored over the given time interval.Results: Both doses of DSF significantly limited the body weight gain caused by an HFD for the treated animals. HF-fed rats received 50 and 200 mg/kg/day of DSF had their body weight increased by 51.93 ± 7.89% and 20.88 ± 15.05% respectively, whereas the body weight of control animals increased by 93.1 ± 20.04%. DSF also significantly decreased the body weight of obese animals. At 50 and 200 mg/kg/day of DSF, HF-fed rats lost 16.74 ± 8.61% and 23.9 ± 3.93% respectively, as their untreated counterparts had their body weight increased by 11.85 ± 3.79% after three weeks of treatment, thus restoring a body weight matching those who received a standard diet.Conclusion: FDA-approved disulfiram has a strong anti-obesity effect on HFD-fed rats.Keywords: obesity, drug repurposing, Aldh1a1, disulfiram
format	article
author	Omran Z Sheikh R Baothman OA Zamzami MA Alarjah M
author_facet	Omran Z Sheikh R Baothman OA Zamzami MA Alarjah M
author_sort	Omran Z
title	Repurposing Disulfiram as an Anti-Obesity Drug: Treating and Preventing Obesity in High-Fat-Fed Rats
title_short	Repurposing Disulfiram as an Anti-Obesity Drug: Treating and Preventing Obesity in High-Fat-Fed Rats
title_full	Repurposing Disulfiram as an Anti-Obesity Drug: Treating and Preventing Obesity in High-Fat-Fed Rats
title_fullStr	Repurposing Disulfiram as an Anti-Obesity Drug: Treating and Preventing Obesity in High-Fat-Fed Rats
title_full_unstemmed	Repurposing Disulfiram as an Anti-Obesity Drug: Treating and Preventing Obesity in High-Fat-Fed Rats
title_sort	repurposing disulfiram as an anti-obesity drug: treating and preventing obesity in high-fat-fed rats
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/e355f663a6c1417dbd0e7b4dc185fd39
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Repurposing Disulfiram as an Anti-Obesity Drug: Treating and Preventing Obesity in High-Fat-Fed Rats

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