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

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.

• Authors: Salim Kemal Tuncer, Seher Altinel, Mehmet Toygar, Hakan Istanbulluoglu, Kahraman Ates, Recai Ogur, Ozcan Altinel, Yildirim Karslioglu, Turgut Topal, Ahmet Korkmaz, Bulent Uysal
• Journal: Inflammopharmacology (Inflammopharmacology) Vol. 24 Issue 4 Pg. 155-61 (Aug 2016) ISSN: 1568-5608 [Electronic] Switzerland
• PMID: 27271689 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Benzamides
• Biomarkers
• Poly(ADP-ribose) Polymerase Inhibitors
• Neopterin
• 3-aminobenzamide
• Poly(ADP-ribose) Polymerases
• Paraquat

Topics

• Animals
• Antioxidants (metabolism)
• Benzamides (administration & dosage, therapeutic use)
• Biomarkers (blood)
• Disease Models, Animal
• Female
• Injections, Intraperitoneal
• Lipid Peroxidation (drug effects)
• Lung Injury (chemically induced, enzymology, pathology, prevention & control)
• Neopterin (blood)
• Paraquat (toxicity)
• Poly(ADP-ribose) Polymerase Inhibitors (administration & dosage, therapeutic use)
• Poly(ADP-ribose) Polymerases (metabolism)
• Rats, Sprague-Dawley