Salim Kemal Tuncer1, Seher Altinel2, Mehmet Toygar3, Hakan Istanbulluoglu4, Kahraman Ates5, Recai Ogur4, Ozcan Altinel6, Yildirim Karslioglu7, Turgut Topal8, Ahmet Korkmaz8, Bulent Uysal9. 1. Department of Emergency Medicine, Gulhane Military Medical Academy, Ankara, Turkey. 2. Department of Anesthesia and Reanimation, Dr. Abdurrahman Yurtaslan, Ankara Oncology Education and Research Hospital, Ankara, Turkey. 3. Department of Forensic Medicine, Gulhane Military Medical Academy, Ankara, Turkey. 4. Department of Public Health, Gulhane Military Medical Academy, Ankara, Turkey. 5. Department of Biophysics, Gulhane Military Medical Academy, Ankara, Turkey. 6. Department of Noncommissioned Officer Health College, Gulhane Military Medical Academy, Ankara, Turkey. 7. Department of Pathology, Gulhane Military Medical Academy, Ankara, Turkey. 8. Department of Physiology, Gulhane Military Medical Academy, Ankara, 06010, Turkey. 9. Department of Physiology, Gulhane Military Medical Academy, Ankara, 06010, Turkey. buysal@gata.edu.tr.
Abstract
OBJECTIVES: Paraquat (PQ) is a widely used herbicide. Exposure to PQ at toxic doses can result in fatal acute lung injury. Inhibition of the poly-(ADP-ribose) polymerase (PARP) enzyme alleviates inflammation and necrosis in various pathologies. Here we aimed to evaluate the effects of PARP inhibition on PQ-induced lung damage in a rat experimental model. METHODS: Female Sprague-Dawley rats (n = 24) were allocated into three groups: sham, PQ and PQ + 3-aminobenzamide (3-AB) that is a PARP inhibitor, groups. Experimental lung injury was induced by administration of 15 mg/kg PQ intraperitoneally in PQ and PQ + 3-AB groups. 3-AB (10 mg/kg twice per day) was administered to the PQ + 3-AB group for four consecutive days. The animals were killed on the fifth day following PQ administration. Lung tissue and blood samples were collected and stored until analysis. RESULTS: Serum lactate dehydrogenase (LDH) and neopterin levels, tissue oxidative stress parameters, transforming growth factor-beta1 (TGF-β) levels and histological injury scores in the PQ + 3-AB group were significantly lower than in the PQ group (P < 0.05, PQ vs. PQ + 3-AB). Total antioxidant capacity in the PQ + 3-AB group was significantly higher than in the PQ group (P < 0.05, PQ + 3-AB vs. PQ). CONCLUSION: Our results suggested that the use of PARP inhibitors following PQ toxicity might be useful for minimizing lung injury due to paraquat toxicity.
OBJECTIVES:Paraquat (PQ) is a widely used herbicide. Exposure to PQ at toxic doses can result in fatal acute lung injury. Inhibition of the poly-(ADP-ribose) polymerase (PARP) enzyme alleviates inflammation and necrosis in various pathologies. Here we aimed to evaluate the effects of PARP inhibition on PQ-induced lung damage in a rat experimental model. METHODS: Female Sprague-Dawley rats (n = 24) were allocated into three groups: sham, PQ and PQ + 3-aminobenzamide (3-AB) that is a PARP inhibitor, groups. Experimental lung injury was induced by administration of 15 mg/kg PQ intraperitoneally in PQ and PQ + 3-AB groups. 3-AB (10 mg/kg twice per day) was administered to the PQ + 3-AB group for four consecutive days. The animals were killed on the fifth day following PQ administration. Lung tissue and blood samples were collected and stored until analysis. RESULTS: Serum lactate dehydrogenase (LDH) and neopterin levels, tissue oxidative stress parameters, transforming growth factor-beta1 (TGF-β) levels and histological injury scores in the PQ + 3-AB group were significantly lower than in the PQ group (P < 0.05, PQ vs. PQ + 3-AB). Total antioxidant capacity in the PQ + 3-AB group was significantly higher than in the PQ group (P < 0.05, PQ + 3-AB vs. PQ). CONCLUSION: Our results suggested that the use of PARP inhibitors following PQtoxicity might be useful for minimizing lung injury due to paraquattoxicity.
Authors: Cathérine Gebhard; Barbara E Stähli; Yi Shi; Giovanni G Camici; Alexander Akhmedov; Lisa Hoegger; Christine Lohmann; Christian M Matter; Paul O Hassa; Michael O Hottiger; Tadeusz Malinski; Thomas F Lüscher; Felix C Tanner Journal: Biochem Biophys Res Commun Date: 2011-10-01 Impact factor: 3.575
Authors: Kazunori Murakami; Perenlei Enkhbaatar; Katsumi Shimoda; Robert A Cox; Ann S Burke; Hal K Hawkins; Lillian D Traber; Frank C Schmalstieg; Andrew L Salzman; Jon G Mabley; Katalin Komjáti; Pál Pacher; Zsuzsanna Zsengellér; Csaba Szabó; Daniel L Traber Journal: Shock Date: 2004-02 Impact factor: 3.454