02 May 2003 : Original article
Therapeutic potential of PARP inhibitors in inflammatory dermatosis
L. Virag, E. Bakondi, P. Bai, K. Erdelyi, E. Szabo, P. Gergely, C. SzaboMed Sci Monit 2003; 9(1): 75-0 :: ID: 15218
Abstract
Several inflammatory skin diseases are characterized by oxidative stress, i.e. production of reactive oxygen and nitrogen intermediates (ROI/RNI). These reactive species are capable of causing DNA damage and consequently PARP activation. Accumulating evidence point toward an important role of oxidative stress-induced PARP activation in various dermatological conditions. Most evidence supports the role of PARP activation in contact hypersensitivity (CHS). CHS is a form of delayed type of hypersensitivity reaction mediated mainly by T lymphocytes. The first phase of CHS is sensitization during which administration of antigens triggers the proliferation of antigen-specific T lymphocytes. In senzitized individuals, application of the same, lipofilic antigen on the skin surface results in immune-mediated inflammation (effector phase). Whereas the cellular events of the senzitization phase is well characterized, little is known about the mechanisms of the effector phase. Our previous work has demonstrated that peroxynitrite, the nitric oxide-derived reactive oxidant is produced in the oxazolone-induced murine model of contact hypersensitivity. Furthermore, we have also shown that DNA breakage and PARP activation occurs in this model. Moreover, our new data demonstrate the effectiveness of the PARP inhibitor PJ-34 in CHS. The underlining mechanisms include inhibition of migration of granulocytes, inhibition of chemokine production and prevention of keratinocyte dysfunction. Sporadic data in the literature also indicate a possible role of PARP activation in other skin diseases such as sunburn erythema, toxic epidermal necrolysis or Stevens-Johnson syndrom. Proposed mechanisms for the role of poly-ADP-ribosylation in these dermatological diseases and opportunities for therapeutic interventions will be discussed.
Keywords: peroxynitrite, poly(ADP-ribose) polymerase, Dermatitis, contact hypersensitivity, Sunburn
Editorial
01 May 2024 : Editorial
Editorial: First Regulatory Approval for Adoptive Cell Therapy with Autologous Tumor-Infiltrating Lymphocytes (TILs) – Lifileucel (Amtagvi)DOI: 10.12659/MSM.944927
Med Sci Monit 2024; 30:e944927
In Press
07 May 2024 : Clinical Research
Treatment of AVN-Induced Proximal Pole Scaphoid Nonunion Using a Fifth and Fourth Extensor Compartmental Ar...Med Sci Monit In Press; DOI: 10.12659/MSM.944553
16 Mar 2024 : Clinical Research
Diagnostic Efficiency of ACR-TIRADS Score for Differentiating Benign and Malignant Thyroid Nodules of Vario...Med Sci Monit In Press; DOI: 10.12659/MSM.943228
08 May 2024 : Clinical Research
Effect of Individualized PEEP Guided by Driving Pressure on Diaphragm Function in Patients Undergoing Lapar...Med Sci Monit In Press; DOI: 10.12659/MSM.944022
21 Mar 2024 : Clinical Research
Impact of Serum Vitamin D, B6, and B12 and Cognitive Functions on Quality of Life in Peri- and Postmenopaus...Med Sci Monit In Press; DOI: 10.12659/MSM.943249
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952