Effects of Pentoxifylline on TNF-Alpha and Lung Histopathology in HCl-Induced Lung Injury

Abstract

To evaluate the effects of pentoxifylline on hydrochloric acid-induced lung lesions in rats subjected to mechanical ventilation. Twenty male, adult Wistar-EPM-1 rats were anesthetized and randomly grouped (n=5 animals per group) as follows: control-MV (mechanical ventilation, MV group); bilateral instillation of HCl (HCl group); bilateral instillation of HCl followed by pentoxifylline (50 mg/kg bw) infusion (HCl+PTX group) and pentoxifylline infusion followed by bilateral instillation of HCl (PTX+HCl group). At 20, 30, 90 and 180 min after treatments, the blood partial pressures of CO2 and O2 were measured. The animals were euthanized, and bronchoalveolar lavages were taken to determine the contents of total proteins, corticosterone [corrected] and TNF-alpha. Samples of lung tissue were used for histomorphometric studies and determining the wet-to-dry (W/D) lung weight ratio. In the MV group, rats had alveolar septal congestion, and, in the HCl group, a remarkable recruitment of neutrophils and macrophages into the alveoli was noticed; these events were reduced in the animals with PTX+HCl. The partial pressure of oxygen increased in PTX+HCl animals (121+/-5 mmHg) as compared with the HCl (62+/-6 mmHg) and HCl+PTX (67+/-3 mmHg) groups within 30 minutes. TNF-alpha levels in bronchoalveolar lavage were significantly higher in the HCl group (458+/-50 pg/mL), reduced in the HCl+PTX group (329+/-45 pg/mL) and lowest in the PTX+HCl group (229+/-41 pg/mL). The levels of corticosterone [corrected] in bronchoalveolar lavage were significantly lower in the HCl (8+/-1.3 ng/mL) and HCl+PTX group (16+/-2 ng/mL) and were highest in the PTX+HCl (27+/-1.9 ng/mL). Pretreatment with PTX improves oxygenation, reduces TNF-alpha concentration and increases the concentration of corticosterone [corrected] in bronchoalveolar lavage upon lung lesion induced by HCl.