Effects of phenacetin, paracetamol and caffeine on the erosive activity of acetylsalicylic acid in the rat stomach: dose-response relationships, time course of erosion development and effects on acid secretion

Abstract

Adult male and female Wistar rats were equally susceptible to gastric injury induced with acetylsalicylic acid (aspirin). Both in male and in female rats simultaneous administration of caffeine and aspirin caused significantly more gastric erosions than the same dose of aspirin alone; likewise addition of paracetamol to aspirin decreased the incidence of gastric lesions in either sex, and addition of phenacetin to aspirin had no effect. The potentiation by caffeine and the inhibition by paracetamol were both dose‐dependent and only markedly influenced the development of erosions after 3–4 h. Pretreatment with phenacetin or paracetamol 1 h before administration of aspirin did not affect its erosive activity. Administration of benorylate caused no more gastric erosions than the vehicle or than equivalent mixtures of aspirin and paracetamol. The histamine‐stimulated acid output of the stomach during gastric perfusion with aspirin was rapidly diminished. Neither paracetamol nor caffeine initially affected this decrease in acid output. However, 30 min after perfusion with aspirin and caffeine, acid secretion increased approximately as strongly as after caffeine alone. Caffeine potentiates aspirin‐induced erosions by its stimulatory effect on acid secretion whereas paracetamol inhibits these erosions by preventing their growth.

The influence of paracetamol on the erosive activity of indomethacin in the rat stomach

“…Median erosion scores with limits including 60% of the observations (n = 10). [8]. Finally, it seems that with doses causing comparable maximal erosion scores the onset and the development of erosions induced with indomethacin were faster than in the case of aspirin [8]; maximal erosion scores were reached after 4 h with indomethacin and after 8 h with aspirin.…”

“…Several PG's are reported to protect the gastric mueosa against the erosive activity of a variety of irritating agents, including NSAID [6,7]. The non-narcotic analgesic, paracetamol, which does not induce gastric damage, was found to protect the rat stomach against the erosive activity of one of the most common NSAID, aspirin [8].…”

“…The time-course of the development of gastric erosions induced by indomethacin was compared with the data obtained by SEEGERS et al [8] with aspirin. …”

Acetaminophen Directly Protects Human Gastric Epithelial Cell Monolayers against Damage Induced by Sodium Taurocholate

“…Van Kolfschoten et al [20] studied the effect of aspirin and acetaminophen on pro duction of prostaglandins in rat gastric mu cosa in vivo. They found no effect of acet aminophen on prostaglandin-I2-like activity production at 0.5, 5 and 17 h after adminis tration; PGE2-like activity was not affected at 0.5 h, increased at 5 h but decreased at 17 h though erosions were decreased at the latter two times [9], Furthermore, the inhib itory effect of aspirin on the production of PGE2-like activity was not affected by con current administration of acetaminophen. They concluded that it was unlikely that acetaminophen protection of gastric mucosa was due to stimulation of prostaglandin syn thesis.…”

“…In vivo studies in rats showed that acetaminophen protects gastric mucosa against acidified aspirin and ethanol [9,10]. Stern et al [ 11 ] demonstrated in man that a single dose of acetaminophen reduces gastric mucosal damage produced by either ethanol or acidified aspirin.…”