Paracetamol potentiates stress-induced gastric ulceration in rats

The effect of paracetamol on gastric ulcers produced by restraint at 4 degrees C for 2 h (stress) was studied in rats. Paracetamol treatment s.c. or p.o., with a dose as high as 250 mg kg-1, did not produce any haemorrhagic lesions in the glandular mucosa. Oral administration with 250 mg kg-1, however, significantly reduced the mast cell count in the gastric glandular mucosa and potentiated haemorrhagic ulceration but not mast cell degranulation caused by stress. The potentiating action was maximum when paracetamol was given between 15 and 30 min before stress. Ranitidine, astemizole, dimethylsulphoxide, sucralfate and verapamil did not protect against the adverse action of paracetamol on stress-evoked lesions. This study suggests that paracetamol worsens stress-induced stomach ulceration by an action which appears not to be due to histamine release, free radical production or intracellular calcium disturbance in the gastric mucosa.