Effects of paracetamol and propacetamol on gastric mucosal damage and gastric lipid peroxidation caused by acetylsalicylic acid (ASA) in rats.

We have studied the effect of paracetamol and its pro-drug propacetamol on gastric mucosal damage induced by acetylsalicylic acid (ASA) and its possible relation to changes in gastric lipid peroxidation status in rats. Paracetamol or propacetamol were administered intragastrically 1h before ASA (300 mg kg(-1)) in the following equivalent doses: 62.5, 125.0 and 250.0 mg kg(-1) or 125.0, 250.0 and 500.0 mg kg(-1), respectively. The effects of the tested agents were compared to that of prostaglandin E2 (PGE2) 15, 30 and 60 mg kg(-1). Gastric ulcer formation was estimated morphometrically 4h after ASA administration. Malondialdehyde (MDA), glutathione (reduced, GSH, and oxidized, GSSG) and uric acid (UA) were determined in gastric mucosa and blood plasma and used as biochemical markers of the oxidative status. The results showed that paracetamol (250, 125, 62.5 mg kg(-1)) and propacetamol (500, 250, 125 mg kg(-1)) diminished the area of ASA-induced gastric lesions. The effect of propacetamol was more pronounced than that of paracetamol and similar to that of PGE2. Gastric MDA increased 3-fold in the ASA-group. The tested agents reduced it by a range of 30-70%. In all pretreated groups gastric glutathione and UA levels were found higher than that of control group and lower than that of ASA-group. Paracetamol and propacetamol, as well as PGE2, diminished the lipid peroxidation in plasma to a lesser extent than in gastric mucosa, but maintained elevated levels of the selective plasma antioxidant UA. These results show that the ASA-induced gastric mucosal damage is accompanied by the development of oxidative stress, evidenced by the accumulation of MDA, and concomitant initial activation of cell antioxidant defences. As paracetamol and propacetamol tend to decrease gastric lesions caused by ASA and alter gastric mucosal MDA, glutathione and UA values in a favorable manner, it could be suggested that their effects on the gastric mucosa could be related to interference with oxidative stress development.

Gastroprotective effect of propacetamol against cold/restraint stress ulcers in rats.

BACKGROUND: Comparative evaluation of propacetamol and morphine on the cold restraint stress ulcers in rats. METHODS: The present study compared the effects of propacetamol hydrochloride (250 and 500 mg.kg-1 i.p.) and morphine hydrochloride (10 mg.kg-1 i.p.) against gastric mucosal damage induced by cold/restraint stress (4 degrees C for 3 h) in rats. Morphometrical and histomorphological studies were carried out. Mean ulcer number and length were calculated. RESULTS: The results show that propacetamol in the lower dose tested decreases the ulcer number and length by 56.4% (p > 0.05) and by 68.94% (p < 0.01). After propacetamol 500 mg.kg-1 the ulcer number and length were found significantly decreased by 74.83% and 83.5%. Marked decrease was found in morphine-pretreated group (-77.03% and -85.09%). The morphometrical results have been confirmed histomorphologically. CONCLUSIONS: It might be concluded that morphine (10 mg.kg-1) and propacetamol (500 mg.kg-1) are equipotent in their ability to prevent the stress ulceration in rats.

[Prevention of aspiration syndrome in general anesthesia]. / Profilaktika na aspiratsionniia sindrom v obshtata anesteziologiia.

In 210 patients divided in 7 groups depending on surgical disease or pregnancy the authors estimated pH of the gastric content during the preoperative period. It was found that pH was below 2.5, i.e. the acid level of the gastric content was high enough to present a hazard for appearance of Mendelson's syndrome, should eventual regurgitation or aspiration occur during or after general anesthesia. In an effort to prevent aspiration syndrome, apart from the most reliable and well know precaution "empty stomach", the authors suggest premedication with antacid drugs before the operation. They have applied Almagel A or Cimetidin 30 min before the operative intervention. The acid level of the gastric juice was thus reduced for about 1 1/2 hours to pH levels higher than the critical 3.5, so that in the event of eventual regurgitation and aspiration the gastric content would not cause severe respiratory injury. With their suggestion for use of antacid drugs during the preoperative period the authors expand the preoperative preparation of the patient for general anesthesia with set purpose to prevent respiration (Mendelson's) syndrome.