Paracetamol and ibuprofen block hydrothorax absorption in mice

Abstract

Objectives: Non-steroidal anti-inflammatory agents (NSAIDs) and paracetamol alter pleural permeability, hindering pleural fluid recycling. The aim of this study was to investigate the effect of different analgesic and anti-inflammatory agents on fluid recycling in an induced hydrothorax model in mice.

Methods: Hydrothorax was induced in C57BL/6 mice by injecting 500 μl phosphate-buffered saline-bovine serum albumin 1% isosmotic in the right hemithorax. Paracetamol (1 g/kg), ibuprofen (250 mg/kg) and parecoxib (2 mg/kg) were administered systematically by intraperitoneal injections. Each drug group included eight mice, which were sacrificed at 2 h and 4 h, respectively, after injections. The remaining hydrothorax volume and total cells contained were determined.

Results: Regarding the paracetamol and ibuprofen groups, the remaining hydrothorax volume was greater than in the control group (350 ± 61, 348 ± 62 and 270 ± 51 μl, respectively, P = 0.042) when mice were sacrificed within 2 h. Similar observations were made in groups sacrificed after 4 h (202 ± 45 and 198 ± 44 vs 107 ± 56 μl, respectively, P = 0.002). In the parecoxib group, the remaining hydrothorax volume was 122 ± 53 μl (P = 0.038 versus paracetamol and ibuprofen, P > 0.05 versus control group). At the same time, the absorption rate in the paracetamol and ibuprofen groups was lower than in the parecoxib and control groups (P = 0.033). In the parecoxib group, the absorption rate was lower than that in the control group after 2 h (P = 0.042). In the paracetamol and ibuprofen groups, the total cell count and the macrophage and the neutrophils counts were increased, compared with the control and parecoxib groups (P = 0.025, 0.028 and 0.032, respectively).

Conclusions: Paracetamol and ibuprofen acutely hinder pleural fluid recycling by lowering the fluid absorption rate (higher remaining hydrothorax volume), while they increased total white cell counts. COX-2s presented lower remaining hydrothorax volume without acutely increasing the absorption rate. These findings could present some relevance to the administration of painkillers in patients with pleural effusion after thoracotomy.

Keywords: Absorption; Hydrothorax; Mice; NSAIDs; Paracetamol; Pleural.