Enhancement of aspirin‐induced gastric damage by cholestasis in rats

Abstract

In this study the severity of aspirin-induced gastric mucosal damage was investigated in rats with obstructive cholestasis. Cholestasis was induced by ligation and resection of the bile duct under general anesthesia. Two weeks after operation, the rats were fasted for 24 hours. Aspirin was administered orally in doses of 0, 128, 192, 266 and 335 mg/kg, and the animals were killed four hours after dosing. The dose of 266 mg/kg was chosen for a study of the time-dependency; other groups of animals were killed at time intervals of one, three, five, seven and nine hours after aspirin administration. The results showed that aspirin induces more severe gastric damage in bile duct resected rats compared with sham-operated and control animals. Salicylate levels of serums were also measured but there was no significant difference in serum salicylate levels between bile duct resected, sham-operated and control rats. It can be concluded that cholestasis can potentiate aspirin-induced gastric damage in rats.

The increased gastroprotective effect of pioglitazone in cholestatic rats: role of nitric oxide and tumour necrosis factor alpha

“…It is well known that fatal upper gastrointestinal bleeding often occurs in critically ill or postoperative patients with obstructive jaundice (Urakawa et al 1987) and the frequency of gastrointestinal ulcerations are higher in jaundiced patients compared with normal population (Bastid et al 1990). Several experimental studies have shown that the gastric mucosa of cholestatic animals is more vulnerable to water-immersion stress (Sasaki et al 1986) and gastroinvasive agents such as aspirin, indomethacin, ethanol and taurocholate (Matsuo et al 1989;Dehpour et al 1998Dehpour et al , 1999Nahavandi et al 2001). Our results in this study also are consistent with previous reports.…”

“…; Dehpour et al . ). The exact mechanism of this increased frequency still remains uncertain, but the most important theory is that it is caused by a decrease in gastric wall blood flow (Sasaki et al .…”

“…The frequency of gastrointestinal ulceration is higher in jaundiced patients than in the normal population (Bastid et al 1990). Experimental studies have shown that the gastric mucosa of cholestatic animals is more vulnerable to stress (Sasaki et al 1986) and to gastroinvasive agents such as aspirin and bile salts than the gastric mucosa of intact animals (Matsuo et al 1989;Dehpour et al 1998). The exact mechanism of this increased frequency still remains uncertain, but the most important theory is that it is caused by a decrease in gastric wall blood flow (Sasaki et al 1986;Urakawa et al 1987).…”

Naloxone is protective against indomethacin-induced gastric damage in cholestatic rats

“…1 Experimental studies have shown that the gastric mucosa of cholestatic animals is more vulnerable to stress, 2 and to gastro-ulcerogenic agents (such as aspirin and bile salts) than the gastric mucosa of intact animals. 3,4 The underlying mechanism(s) of the greater mucosal damage in subjects with cholestasis is not clear, but the most important theory is that it is caused by a decrease in gastric wall blood flow. 5 Previous reports have also referred to increased gastric acid output, 2 and decreased mucosal noradrenaline and prostaglardin E 2 (PGE 2 ), 5 and increased free radical formation 6,7 in rats with obstructive cholestasis.…”

Effects of melatonin or acetylsalicylic acid on gastric oxidative stress after bile duct ligation in rats

“…On the other hand, some reports indicate that ASA induces free radical formation. [15][16][17][18][19] In the present study, we compared the effects of melatonin and acetylsalicylic acid on gastric oxidative stress induced by bile duct ligation. We also evaluated the activities of antioxidant enzymes, namely, SOD, CAT, and GPx, and we measured levels of NO, and malondialdehyde (MDA) in rat gastric tissue.…”