PARP Inhibitors: An Innovative Approach to the Treatment of Inflammation and Metabolic Disorders in Sepsis

Weronika Wasyluk,1,2 Agnieszka Zwolak1 1Chair of Internal Medicine and Department of Internal Medicine in Nursing, Faculty of Health Sciences, Medical University of Lublin, Lublin, Poland; 2Doctoral School, Medical University of Lublin, Lublin, PolandCorrespondence: Weronika WasylukChair of Internal...

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Autores principales:	Wasyluk W, Zwolak A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	sepsis septic shock inflammation metabolism poly(adp-ribose) polymerases parp inhibitors Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/b81ae721ef1448789419dd5e916dbe06
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spelling	oai:doaj.org-article:b81ae721ef1448789419dd5e916dbe062021-12-02T14:47:43ZPARP Inhibitors: An Innovative Approach to the Treatment of Inflammation and Metabolic Disorders in Sepsis1178-7031https://doaj.org/article/b81ae721ef1448789419dd5e916dbe062021-05-01T00:00:00Zhttps://www.dovepress.com/parp-inhibitors-an-innovative-approach-to-the-treatment-of-inflammatio-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Weronika Wasyluk,1,2 Agnieszka Zwolak1 1Chair of Internal Medicine and Department of Internal Medicine in Nursing, Faculty of Health Sciences, Medical University of Lublin, Lublin, Poland; 2Doctoral School, Medical University of Lublin, Lublin, PolandCorrespondence: Weronika WasylukChair of Internal Medicine and Department of Internal Medicine in Nursing, Faculty of Health Sciences, Medical University of Lublin, Ul. Witolda Chodźki 7, Lublin, 20-093, PolandTel +48 81 448 7720Email weronika.wasyluk@gmail.comAbstract: Sepsis is not only a threat to the health of individual patients but also presents a serious epidemiological problem. Despite intensive research, modern sepsis therapy remains based primarily on antimicrobial treatment and supporting the functions of failing organs. Finding a cure for sepsis represents a great and as yet unfulfilled need in modern medicine. Research results indicate that the activity of poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) may play an important role in the inflammatory response and the cellular metabolic disorders found in sepsis. Mechanisms by which PARP-1 may contribute to inflammation and metabolic disorders include effects on the regulation of gene expression, impaired metabolism, cell death, and the release of alarmins. These findings suggest that inhibition of this enzyme may be a promising solution for the treatment of sepsis. In studies using experimental sepsis models, inhibition of PARP-1 has been shown to ameliorate the inflammatory response and increase survival. This action was described, among others, for olaparib, a PARP-1 inhibitor approved for use in oncology. While the results of current research are promising, the use of PARP inhibitors in non-oncological diseases raises some concerns, mainly related to the enzyme’s role in deoxyribonucleic acid (DNA) repair. However, the results of studies on experimental models indicate the effectiveness of even short-term PARP-1 inhibition and do not confirm concerns regarding its impact on the integrity of nuclear DNA. Current research presents PARP inhibition as a potential solution for the treatment of sepsis and indicates the need for further research.Keywords: sepsis, septic shock, inflammation, metabolism, poly(ADP-ribose) polymerases, PARP inhibitorsWasyluk WZwolak ADove Medical Pressarticlesepsisseptic shockinflammationmetabolismpoly(adp-ribose) polymerasesparp inhibitorsPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 1827-1844 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	sepsis septic shock inflammation metabolism poly(adp-ribose) polymerases parp inhibitors Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	sepsis septic shock inflammation metabolism poly(adp-ribose) polymerases parp inhibitors Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Wasyluk W Zwolak A PARP Inhibitors: An Innovative Approach to the Treatment of Inflammation and Metabolic Disorders in Sepsis
description	Weronika Wasyluk,1,2 Agnieszka Zwolak1 1Chair of Internal Medicine and Department of Internal Medicine in Nursing, Faculty of Health Sciences, Medical University of Lublin, Lublin, Poland; 2Doctoral School, Medical University of Lublin, Lublin, PolandCorrespondence: Weronika WasylukChair of Internal Medicine and Department of Internal Medicine in Nursing, Faculty of Health Sciences, Medical University of Lublin, Ul. Witolda Chodźki 7, Lublin, 20-093, PolandTel +48 81 448 7720Email weronika.wasyluk@gmail.comAbstract: Sepsis is not only a threat to the health of individual patients but also presents a serious epidemiological problem. Despite intensive research, modern sepsis therapy remains based primarily on antimicrobial treatment and supporting the functions of failing organs. Finding a cure for sepsis represents a great and as yet unfulfilled need in modern medicine. Research results indicate that the activity of poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) may play an important role in the inflammatory response and the cellular metabolic disorders found in sepsis. Mechanisms by which PARP-1 may contribute to inflammation and metabolic disorders include effects on the regulation of gene expression, impaired metabolism, cell death, and the release of alarmins. These findings suggest that inhibition of this enzyme may be a promising solution for the treatment of sepsis. In studies using experimental sepsis models, inhibition of PARP-1 has been shown to ameliorate the inflammatory response and increase survival. This action was described, among others, for olaparib, a PARP-1 inhibitor approved for use in oncology. While the results of current research are promising, the use of PARP inhibitors in non-oncological diseases raises some concerns, mainly related to the enzyme’s role in deoxyribonucleic acid (DNA) repair. However, the results of studies on experimental models indicate the effectiveness of even short-term PARP-1 inhibition and do not confirm concerns regarding its impact on the integrity of nuclear DNA. Current research presents PARP inhibition as a potential solution for the treatment of sepsis and indicates the need for further research.Keywords: sepsis, septic shock, inflammation, metabolism, poly(ADP-ribose) polymerases, PARP inhibitors
format	article
author	Wasyluk W Zwolak A
author_facet	Wasyluk W Zwolak A
author_sort	Wasyluk W
title	PARP Inhibitors: An Innovative Approach to the Treatment of Inflammation and Metabolic Disorders in Sepsis
title_short	PARP Inhibitors: An Innovative Approach to the Treatment of Inflammation and Metabolic Disorders in Sepsis
title_full	PARP Inhibitors: An Innovative Approach to the Treatment of Inflammation and Metabolic Disorders in Sepsis
title_fullStr	PARP Inhibitors: An Innovative Approach to the Treatment of Inflammation and Metabolic Disorders in Sepsis
title_full_unstemmed	PARP Inhibitors: An Innovative Approach to the Treatment of Inflammation and Metabolic Disorders in Sepsis
title_sort	parp inhibitors: an innovative approach to the treatment of inflammation and metabolic disorders in sepsis
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/b81ae721ef1448789419dd5e916dbe06
work_keys_str_mv	AT wasylukw parpinhibitorsaninnovativeapproachtothetreatmentofinflammationandmetabolicdisordersinsepsis AT zwolaka parpinhibitorsaninnovativeapproachtothetreatmentofinflammationandmetabolicdisordersinsepsis
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PARP Inhibitors: An Innovative Approach to the Treatment of Inflammation and Metabolic Disorders in Sepsis

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