Poly-ADP-ribose polymerase inhibition provides protection against lung injury in a rat paraquat toxicity model.
OBJECTIVE
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).


CONCLUSIONS
Our results suggested that the use of PARP inhibitors following PQ toxicity might be useful for minimizing lung injury due to paraquat toxicity.
Department of Emergency Medicine, Gulhane Military Medical Academy, Ankara, Turkey.
Salim Kemal
SK
Tuncer
Department of Anesthesia and Reanimation, Dr. Abdurrahman Yurtaslan, Ankara Oncology Education and Research Hospital, Ankara, Turkey.
Seher
S
Altinel
Department of Forensic Medicine, Gulhane Military Medical Academy, Ankara, Turkey.
Mehmet
M
Toygar
Department of Public Health, Gulhane Military Medical Academy, Ankara, Turkey.
Hakan
H
Istanbulluoglu
Department of Biophysics, Gulhane Military Medical Academy, Ankara, Turkey.
Kahraman
K
Ates
Department of Public Health, Gulhane Military Medical Academy, Ankara, Turkey.
Recai
R
Ogur
Department of Noncommissioned Officer Health College, Gulhane Military Medical Academy, Ankara, Turkey.
Ozcan
O
Altinel
Department of Pathology, Gulhane Military Medical Academy, Ankara, Turkey.
Yildirim
Y
Karslioglu
Department of Physiology, Gulhane Military Medical Academy, Ankara, 06010, Turkey.
Turgut
T
Topal
Department of Physiology, Gulhane Military Medical Academy, Ankara, 06010, Turkey.
Ahmet
A
Korkmaz
Department of Physiology, Gulhane Military Medical Academy, Ankara, 06010, Turkey. buysal@gata.edu.tr.
Bulent
B
Uysal
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001549:Benzamides / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D055370:Lung Injury / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D019798:Neopterin / Q000097:blood; D010269:Paraquat / Q000633:toxicity*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D001549:Benzamides; D015415:Biomarkers; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D019798:Neopterin; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases; D010269:Paraquat
Lung injury; Neopterin; PARP inhibition; Paraquat toxicity; TGF-β1