DPQ

DPQ is a potent, blood-brain barrier-permeable poly(ADP-ribose) polymerase-1 (PARP-1) selective inhibitor used to study DNA damage repair and related cellular processes^[1-2]. DPQ can be applied to investigate inflammatory responses and cell death mechanisms in acute lung injury, myocardial ischemia-reperfusion injury, and neurodegenerative diseases, demonstrating neuroprotective and cardioprotective effects^[3-4].

In vitro, pretreatment of non-small cell lung cancer cells (A549 and H1299) with DPQ (1μM) for 4 hours, followed by carbon ion irradiation (0.5–2Gy) for 24 hours, significantly inhibited cell migration, wound healing capacity, and the activity and expression of matrix metalloproteinases (MMP-2 and MMP-9)^[5]. Pretreatment of HeLa cells with DPQ (20–150μM) for 1 hour, followed by stimulation with PMA (50nM) for 3 hours, significantly suppressed the upregulation of histamine H1 receptor (H1R) gene expression and reduced H1R promoter activity^[6].

In vivo, pretreatment of C57BL/6 mice with DPQ (15mg/kg) 24 hours before renal ischemia for 45 minutes/reperfusion for 6 hours reduced ischemia-reperfusion-related pathological damage, such as acute tubular necrosis (ATN), tubular cell vacuolization, and brush border loss, by inhibiting PARP-1 overactivation, while also ameliorating tubular epithelial cell shedding and cast formation^[7]. Pretreatment of C57BL/6 mice with LPS (7.5mg/kg) for 30 minutes, followed by intraperitoneal injection of DPQ (10μg/kg) for 6 hours, significantly inhibited neutrophil infiltration and myeloperoxidase (MPO) activity in lung tissue, while reducing the mRNA expression levels of pro-inflammatory factors such as TNF-α, IL-1β, and IL-6^[8].

References:
[1] Meli E, Pangallo M, Picca R, et al. Differential role of poly(ADP-ribose) polymerase-1in apoptotic and necrotic neuronal death induced by mild or intense NMDA exposure in vitro. Mol Cell Neurosci. 2004 Jan;25(1):172-80.
[2] Wang J, Hao L, Wang Y, et al. Inhibition of poly (ADP-ribose) polymerase and inducible nitric oxide synthase protects against ischemic myocardial damage by reduction of apoptosis. Mol Med Rep. 2015 Mar;11(3):1768-76.
[3] Czapski GA, Cakala M, Kopczuk D, et al. Effect of poly(ADP-ribose) polymerase inhibitors on oxidative stress evoked hydroxyl radical level and macromolecules oxidation in cell free system of rat brain cortex. Neurosci Lett. 2004 Feb 6;356(1):45-8.
[4] Suh SW, Aoyama K, Alano CC, et al. Zinc inhibits astrocyte glutamate uptake by activation of poly(ADP-ribose) polymerase-1. Mol Med. 2007 Jul-Aug;13(7-8):344-9.
[5] Chowdhury P, Dey P, Ghosh S, et al. Reduction of metastatic potential by inhibiting EGFR/Akt/p38/ERK signaling pathway and epithelial-mesenchymal transition after carbon ion exposure is potentiated by PARP-1 inhibition in non-small-cell lung cancer. BMC Cancer. 2019 Aug 22;19(1):829.
[6] Mizuguchi H, Terao T, Kitai M, et al. Involvement of protein kinase Cdelta/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expression in HeLa cells. J Biol Chem. 2011 Sep 2;286(35):30542-30551.
[7] del Moral RM, Gómez-Morales M, Hernández-Cortés P, et al. PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal mouse model after cold prolonged ischemia. ScientificWorldJournal. 2013 Nov 11;2013:486574.
[8] Wang G, Huang X, Li Y, et al. PARP-1 inhibitor, DPQ, attenuates LPS-induced acute lung injury through inhibiting NF-κB-mediated inflammatory response. PLoS One. 2013 Nov 21;8(11):e79757.