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

• Published in: Journal of inflammation research 2021-01, Vol.14, p.1827-1844
• Main Authors: Wasyluk, Weronika, Zwolak, Agnieszka
• Format: Article
• Language: English
• Subjects: 20th century; Adenosine; Adenosine triphosphatase; Amino acids; Analysis; Care and treatment; Cell death; Cell division; Deoxyribonucleic acid; DNA; DNA repair; Enzymes; Epidemiology; Gene expression; Health aspects; Infection; Infections; Inflammation; Intensive care; Metabolic disorders; metabolism; Monosaccharides; Mortality; Nucleic acids; parp inhibitors; Pathogens; Physiological aspects; Poly(ADP-ribose) polymerase; poly(adp-ribose) polymerases; Polymers; Proteins; Review; Ribose; Sepsis; Septic shock; Sugars; Targeted cancer therapy
• ISSN: 1178-7031; 1178-7031
• DOI: 10.2147/JIR.S300679

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.