INT99348
From wiki-pain
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Sentences Mentioned In
Key: | Protein | Mutation | Event | Anatomy | Negation | Speculation | Pain term | Disease term |
However, the potential toxicity of complete PARP inhibition necessitates the utilization of weaker PARP inhibitors with additional therapeutic properties. | |||||||||||||||
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In cultured MNCs from healthy subjects, inhibition of PARP-1 prevented lipopolysaccharide-induced increase in DNA binding activity of NF-kappaB and the expression of TNF-alpha and IL-6. | |||||||||||||||
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Poly(ADP-ribose) polymerase (PARP) inhibition has recently been identified as a novel approach to treatment of experimental peripheral diabetic neuropathy (PDN). | |||||||||||||||
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However, long-term inhibition of PARP, an enzyme involved in DNA repair, can potentially result in premature aging, loss of genome stability, and other side effects. | |||||||||||||||
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The cytoprotective effect of dipyrone is associated with a decrease in DNA fragmentation, as assessed by electrophoresis of genomic DNA and by flow cytometry; a reduction in the percentage of condensed nuclei, as evaluated by DNA staining with Hoescht 33342 and a decrease in poly(ADP)-ribose polymerase (PARP) cleavage, as assessed by Western blotting. | |||||||||||||||
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Although PJ-34 is a pharmacological inhibitor of PARP independent on the activating stimuli [5,16], WW85 is a novel metalloporphyrinic peroxynitrite decomposition catalyst, releasing of NO3. | |||||||||||||||
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Nicotinamide (vitamin B3) is a weak PARP inhibitor, antioxidant, and calcium modulator and can improve energy status and inhibit cell death in ischemic tissues. | |||||||||||||||
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PARP-1 is inhibited by nicotinamide and its analogues such as 3-aminobenzamide and metoclopramide [112, 113]. | |||||||||||||||
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Nicotinamide as a precursor of NAD+, ATP, and as an endogenous inhibitor of PARP-1 therefore plays significant roles in cellular protection and in determining cellular fate in response to genotoxic DNA damage.
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In various murine models, PARP-1 inhibition was shown to favor apoptotic cell death, reduce inflammatory response, and reduce genomic sensitivity to various carcinogens. | |||||||||||||||
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While PARP-1 inhibition could impair its role in DNA repair, PARP-1 overactivation is detrimental to the cells by depleting its substrate NAD+, which leads to cellular energy crisis and necrotic cell death. | |||||||||||||||
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The expression levels of heat shock protein 70 (HSP70), c-jun and c-fos genes were remarkably up-regulated and those of c-myc and poly (ADP ribose) polymerase (PARP) were down-regulated in bupivacaine-treated cells. | |||||||||||||||
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The inhibitor of caspase-3 blocked PARP-1 cleavage activity and protected against MEF-induced apoptotic cell death. | |||||||||||||||
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Finally, although unlikely according to the literature, we can not exclude that WW85 or PJ-34 affect microcirculatory hemodynamics with other mechanisms other than through catalysation of peroxynitrite decomposition and PARP inhibition, respectively.
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Anesthetized Sprague Dawley rats (n = 31), were subjected to intratracheal instillation of lipopolysaccharide at 10 mg/kg followed by 210 min of mechanical ventilation at either low tidal volume (6 mL/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (19 mL/kg) with zero positive end-expiratory pressure in the presence or absence of a peroxynitrite decomposition catalyst, WW85 or a PARP inhibitor, PJ-34. | |||||||||||||||
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Our current study extends previous observations [5] by further exploring the route of PARP inhibition involved in renal hemodynamic during LPS-induced lung injury aggravated by MV. | |||||||||||||||
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The lung wet/dry ratio was higher in the high Vt+Vehicle than in the low Vt+Vehicle group, and the treatment with the peroxynitrite decomposition catalyst or PARP inhibitor attenuated lung edema (Figure 2b).
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Peroxynitrite formation and PARP activation in lungs of animals with VILI have been demonstrated before [5,16,27] and our current study extends previous observations [5] by further exploring the route of PARP inhibition involved in renal hemodynamics during LPS-induced lung injury aggravated by MV. | |||||||||||||||
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We demonstrated that inhibition of PARP activation by peroxynitrite attenuates VILI and renal hypoperfusion and dysfunction, by maintaining endothelium-dependent vasodilation and decreasing inflammation and tissue injury.
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The compound thus blocks peroxynitrite and thereby reduces PARP activation [24-26]. | |||||||||||||||
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