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Inhibitors of poly(ADP-ribose) polymerase modulate signal transduction pathways and the development of bleomycin-induced lung injury.
J Pharmacol Exp Ther. 2005 May; 313(2):529-38.JP

Abstract

Poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the tissue injury associated with inflammation. The aim of our study was to evaluate the therapeutic efficacy of in vivo inhibition of PARP in an experimental model of lung injury caused by bleomycin administration. Mice subjected to intratracheal administration of bleomycin developed significant lung injury and apoptosis (measured by Annexin V coloration). An increase of immunoreactivity to nitrotyrosine and PARP, as well as a significant loss of body weight and mortality, was observed in the lung of bleomycin-treated mice. Administration of the two PARP inhibitors 3-aminobenzamide (3-AB) or 5-aminoisoquinolinone (5-AIQ) significantly reduced the 1) loss of body weight, 2) mortality rate, 3) infiltration of the lung with polymorphonuclear neutrophils (myeloperoxidase activity), 4) edema formation, and 5) histological evidence of lung injury. Administration of 3-AB and 5-AIQ also markedly reduced nitrotyrosine formation and PARP activation. These results demonstrate that treatment with PARP inhibitors reduces the development of inflammation and tissue injury events induced by bleomycin administration in the mice.

Authors+Show Affiliations

Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15644425

Citation

Genovese, Tiziana, et al. "Inhibitors of poly(ADP-ribose) Polymerase Modulate Signal Transduction Pathways and the Development of Bleomycin-induced Lung Injury." The Journal of Pharmacology and Experimental Therapeutics, vol. 313, no. 2, 2005, pp. 529-38.
Genovese T, Mazzon E, Di Paola R, et al. Inhibitors of poly(ADP-ribose) polymerase modulate signal transduction pathways and the development of bleomycin-induced lung injury. J Pharmacol Exp Ther. 2005;313(2):529-38.
Genovese, T., Mazzon, E., Di Paola, R., Muià, C., Threadgill, M. D., Caputi, A. P., Thiemermann, C., & Cuzzocrea, S. (2005). Inhibitors of poly(ADP-ribose) polymerase modulate signal transduction pathways and the development of bleomycin-induced lung injury. The Journal of Pharmacology and Experimental Therapeutics, 313(2), 529-38.
Genovese T, et al. Inhibitors of poly(ADP-ribose) Polymerase Modulate Signal Transduction Pathways and the Development of Bleomycin-induced Lung Injury. J Pharmacol Exp Ther. 2005;313(2):529-38. PubMed PMID: 15644425.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibitors of poly(ADP-ribose) polymerase modulate signal transduction pathways and the development of bleomycin-induced lung injury. AU - Genovese,Tiziana, AU - Mazzon,Emanuela, AU - Di Paola,Rosanna, AU - Muià,Carmelo, AU - Threadgill,Michael D, AU - Caputi,Achille P, AU - Thiemermann,Christoph, AU - Cuzzocrea,Salvatore, Y1 - 2005/01/11/ PY - 2005/1/13/pubmed PY - 2005/7/6/medline PY - 2005/1/13/entrez SP - 529 EP - 38 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 313 IS - 2 N2 - Poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the tissue injury associated with inflammation. The aim of our study was to evaluate the therapeutic efficacy of in vivo inhibition of PARP in an experimental model of lung injury caused by bleomycin administration. Mice subjected to intratracheal administration of bleomycin developed significant lung injury and apoptosis (measured by Annexin V coloration). An increase of immunoreactivity to nitrotyrosine and PARP, as well as a significant loss of body weight and mortality, was observed in the lung of bleomycin-treated mice. Administration of the two PARP inhibitors 3-aminobenzamide (3-AB) or 5-aminoisoquinolinone (5-AIQ) significantly reduced the 1) loss of body weight, 2) mortality rate, 3) infiltration of the lung with polymorphonuclear neutrophils (myeloperoxidase activity), 4) edema formation, and 5) histological evidence of lung injury. Administration of 3-AB and 5-AIQ also markedly reduced nitrotyrosine formation and PARP activation. These results demonstrate that treatment with PARP inhibitors reduces the development of inflammation and tissue injury events induced by bleomycin administration in the mice. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/15644425/Inhibitors_of_poly_ADP_ribose__polymerase_modulate_signal_transduction_pathways_and_the_development_of_bleomycin_induced_lung_injury_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15644425 DB - PRIME DP - Unbound Medicine ER -