Matches in SemOpenAlex for { <https://semopenalex.org/work/W4310211229> ?p ?o ?g. }
- W4310211229 endingPage "3789" @default.
- W4310211229 startingPage "3789" @default.
- W4310211229 abstract "Poly(ADP-ribose) polymerase 1 (PARP1), as a potential target for the experimental therapy of acute lung injury (ALI), was identified over 20 years ago. However, clinical translation of this concept was not possible due to the lack of clinically useful PARP inhibitors. With the clinical introduction of several novel, ultrapotent PARP inhibitors, the concept of PARP inhibitor repurposing has re-emerged. Here, we evaluated the effect of 5 clinical-stage PARP inhibitors in oxidatively stressed cultured human epithelial cells and monocytes in vitro and demonstrated that all inhibitors (1–30 µM) provide a comparable degree of cytoprotection. Subsequent in vivo studies using a murine model of ALI compared the efficacy of olaparib and rucaparib. Both inhibitors (1–10 mg/kg) provided beneficial effects against lung extravasation and pro-inflammatory mediator production—both in pre- and post-treatment paradigms. The underlying mechanisms include protection against cell dysfunction/necrosis, inhibition of NF-kB and caspase 3 activation, suppression of the NLRP3 inflammasome, and the modulation of pro-inflammatory mediators. Importantly, the efficacy of PARP inhibitors was demonstrated without any potentiation of DNA damage, at least as assessed by the TUNEL method. These results support the concept that clinically approved PARP inhibitors may be repurposable for the experimental therapy of ALI." @default.
- W4310211229 created "2022-11-30" @default.
- W4310211229 creator A5018683554 @default.
- W4310211229 creator A5058049602 @default.
- W4310211229 creator A5068674408 @default.
- W4310211229 creator A5073503915 @default.
- W4310211229 creator A5079261852 @default.
- W4310211229 creator A5089530606 @default.
- W4310211229 date "2022-11-26" @default.
- W4310211229 modified "2023-10-01" @default.
- W4310211229 title "Efficacy of Clinically Used PARP Inhibitors in a Murine Model of Acute Lung Injury" @default.
- W4310211229 cites W1489071015 @default.
- W4310211229 cites W1499143025 @default.
- W4310211229 cites W1581913363 @default.
- W4310211229 cites W1964531991 @default.
- W4310211229 cites W1964968607 @default.
- W4310211229 cites W1967727360 @default.
- W4310211229 cites W1986824378 @default.
- W4310211229 cites W1992363536 @default.
- W4310211229 cites W1994011134 @default.
- W4310211229 cites W2009781172 @default.
- W4310211229 cites W2014484730 @default.
- W4310211229 cites W2017462648 @default.
- W4310211229 cites W2031885286 @default.
- W4310211229 cites W2035192573 @default.
- W4310211229 cites W2037820827 @default.
- W4310211229 cites W2044390268 @default.
- W4310211229 cites W2061298493 @default.
- W4310211229 cites W2061419115 @default.
- W4310211229 cites W2062747680 @default.
- W4310211229 cites W2065139599 @default.
- W4310211229 cites W2082618949 @default.
- W4310211229 cites W2086071317 @default.
- W4310211229 cites W2091328460 @default.
- W4310211229 cites W2092453902 @default.
- W4310211229 cites W2095798342 @default.
- W4310211229 cites W2098737737 @default.
- W4310211229 cites W2099904057 @default.
- W4310211229 cites W2104237068 @default.
- W4310211229 cites W2113807212 @default.
- W4310211229 cites W2114487246 @default.
- W4310211229 cites W2118000448 @default.
- W4310211229 cites W2121092271 @default.
- W4310211229 cites W2121144894 @default.
- W4310211229 cites W2123326944 @default.
- W4310211229 cites W2133771754 @default.
- W4310211229 cites W2134228124 @default.
- W4310211229 cites W2147521003 @default.
- W4310211229 cites W2148430259 @default.
- W4310211229 cites W2159922156 @default.
- W4310211229 cites W2160220971 @default.
- W4310211229 cites W2335177832 @default.
- W4310211229 cites W2412632611 @default.
- W4310211229 cites W2418754718 @default.
- W4310211229 cites W2542632279 @default.
- W4310211229 cites W2588135595 @default.
- W4310211229 cites W2612277616 @default.
- W4310211229 cites W2750626054 @default.
- W4310211229 cites W2790932079 @default.
- W4310211229 cites W2807450905 @default.
- W4310211229 cites W2895012854 @default.
- W4310211229 cites W2936628798 @default.
- W4310211229 cites W2944110805 @default.
- W4310211229 cites W2954782052 @default.
- W4310211229 cites W2973975455 @default.
- W4310211229 cites W2989981864 @default.
- W4310211229 cites W3008619716 @default.
- W4310211229 cites W3013143840 @default.
- W4310211229 cites W3014880483 @default.
- W4310211229 cites W3035340427 @default.
- W4310211229 cites W3040809597 @default.
- W4310211229 cites W3080460871 @default.
- W4310211229 cites W3081569548 @default.
- W4310211229 cites W3081798990 @default.
- W4310211229 cites W3092261196 @default.
- W4310211229 cites W3092592099 @default.
- W4310211229 cites W3114797453 @default.
- W4310211229 cites W3118684161 @default.
- W4310211229 cites W3141522254 @default.
- W4310211229 cites W3199641012 @default.
- W4310211229 cites W3208732148 @default.
- W4310211229 cites W3214965950 @default.
- W4310211229 cites W4210408852 @default.
- W4310211229 cites W4213043054 @default.
- W4310211229 cites W4213115859 @default.
- W4310211229 cites W4214673393 @default.
- W4310211229 cites W4220779662 @default.
- W4310211229 cites W4225793664 @default.
- W4310211229 cites W4226055543 @default.
- W4310211229 cites W4281645714 @default.
- W4310211229 cites W4313309945 @default.
- W4310211229 doi "https://doi.org/10.3390/cells11233789" @default.
- W4310211229 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36497049" @default.
- W4310211229 hasPublicationYear "2022" @default.
- W4310211229 type Work @default.
- W4310211229 citedByCount "2" @default.
- W4310211229 countsByYear W43102112292023 @default.
- W4310211229 crossrefType "journal-article" @default.