• 225 Views
  • 83 Downloads
Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 1 (2011), Issue 1, pp. 9-21
doi:10.11131/2011/101327

Mitigation of Delayed Sodium Hypochlorite-Induced Lung Injury by Phosphodiesterase Enzyme Inhibitors (PDEIs), Pentoxifylline and Theophylline, in Guinea Pigs

Sawsan Aboul-Fotouh1 and Ghada M. Farouk2

1Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

2Department of Histology, Faculty of Medicine, Ain Shams University, Cairo, Egypt


Copyright © 2011 Sawsan Aboul-Fotouh and Ghada M. Farouk. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Sodium hypochlorite (NaOCI) is widely used as an industrial material as well as an ingredient in household cleaning products. Exposure to high concentrations of NaOCl, a powerful oxidant, results in acute lung injury that may proceed to delayed airway hyper responsiveness and remodeling. The present study aims at investigating the effects of two nonselective PDEIs, pentoxifylline ‘PTX’ and theophylline ‘THEO‘, versus dexamethasone ‘DEX’ on delayed airway functional and histopathological injury induced by NaOClinhalation in guinea pigs. Forty-eight guinea pigs were classified into 8 groups; 2 groups (control, 4% NaOClinhalation for 20 min) and another 6 groups were exposed to NaOCl and administrated intraperitoneally vehicle, PTX (50 mg/kg/day), THEO (50 mg/kg/day), DEX (20 mg/kg/day), PTX+DEX or THEO+DEX for 3 weeks. Guinea pigs were assessed for airway functional, biochemical and histopathological dysfunctions. Treatment with PENT or THEO, as monotherapy or in combination with DEX, reduced airway resistance and bronchial reactivity to methacholine. Similar findings were noticed with inflammatory markers such as total cell count, neutrophil percentage and TNF-α in bronchoalveolar lavage and lung myeloperoxidase activity and neutrophil infiltration. These data were parallel to lung histopathology and Aschorft fibrosis score that were improved in treatment groups. PENT, but not THEO or DEX could ameliorate oxidative stress biomarkers, malondialdehyde and superoxide dismutase, in lungs. Co-administration of PENT or THEO with DEX improved the effect of DEX on NaOCl-induced airway injury. In conclusion, ‘PENT and THEO’ are effective in mitigation of delayed NaOCl-induced lung injury in guinea pigs and if these findings were to translate into actual clinical benefit, they might provide a suitable alternative to corticosteroids or at least, reduce its dose needed in management of NaOCl and chlorine-induced lung toxicity.

Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 1 (2011), Issue 1, pp. 9-21
doi:10.11131/2011/101327

Mitigation of Delayed Sodium Hypochlorite-Induced Lung Injury by Phosphodiesterase Enzyme Inhibitors (PDEIs), Pentoxifylline and Theophylline, in Guinea Pigs

Sawsan Aboul-Fotouh1 and Ghada M. Farouk2

1Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

2Department of Histology, Faculty of Medicine, Ain Shams University, Cairo, Egypt


Copyright © 2011 Sawsan Aboul-Fotouh and Ghada M. Farouk. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Sodium hypochlorite (NaOCI) is widely used as an industrial material as well as an ingredient in household cleaning products. Exposure to high concentrations of NaOCl, a powerful oxidant, results in acute lung injury that may proceed to delayed airway hyper responsiveness and remodeling. The present study aims at investigating the effects of two nonselective PDEIs, pentoxifylline ‘PTX’ and theophylline ‘THEO‘, versus dexamethasone ‘DEX’ on delayed airway functional and histopathological injury induced by NaOClinhalation in guinea pigs. Forty-eight guinea pigs were classified into 8 groups; 2 groups (control, 4% NaOClinhalation for 20 min) and another 6 groups were exposed to NaOCl and administrated intraperitoneally vehicle, PTX (50 mg/kg/day), THEO (50 mg/kg/day), DEX (20 mg/kg/day), PTX+DEX or THEO+DEX for 3 weeks. Guinea pigs were assessed for airway functional, biochemical and histopathological dysfunctions. Treatment with PENT or THEO, as monotherapy or in combination with DEX, reduced airway resistance and bronchial reactivity to methacholine. Similar findings were noticed with inflammatory markers such as total cell count, neutrophil percentage and TNF-α in bronchoalveolar lavage and lung myeloperoxidase activity and neutrophil infiltration. These data were parallel to lung histopathology and Aschorft fibrosis score that were improved in treatment groups. PENT, but not THEO or DEX could ameliorate oxidative stress biomarkers, malondialdehyde and superoxide dismutase, in lungs. Co-administration of PENT or THEO with DEX improved the effect of DEX on NaOCl-induced airway injury. In conclusion, ‘PENT and THEO’ are effective in mitigation of delayed NaOCl-induced lung injury in guinea pigs and if these findings were to translate into actual clinical benefit, they might provide a suitable alternative to corticosteroids or at least, reduce its dose needed in management of NaOCl and chlorine-induced lung toxicity.

Original Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 1 (2011), Issue 1, pp. 9-21
doi:10.11131/2011/101327

Mitigation of Delayed Sodium Hypochlorite-Induced Lung Injury by Phosphodiesterase Enzyme Inhibitors (PDEIs), Pentoxifylline and Theophylline, in Guinea Pigs

Sawsan Aboul-Fotouh1 and Ghada M. Farouk2

1Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

2Department of Histology, Faculty of Medicine, Ain Shams University, Cairo, Egypt


Copyright © 2011 Sawsan Aboul-Fotouh and Ghada M. Farouk. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to Cite this Article

Sawsan Aboul-Fotouh and Ghada M. Farouk, “Mitigation of Delayed Sodium Hypochlorite-Induced Lung Injury by Phosphodiesterase Enzyme Inhibitors (PDEIs), Pentoxifylline and Theophylline, in Guinea Pigs,” Egyptian Journal of Basic and Clinical Pharmacology, vol. 1, Issue 1, pp. 9-21, 2011. doi:10.11131/2011/101327