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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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2021
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| Acceso en línea: | https://doaj.org/article/b81ae721ef1448789419dd5e916dbe06 |
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| Sumario: | 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 |
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