Role of oxygen-derived free radicals in mechanism of acute and chronic duodenal ulceration in the rat

Abstract

This study employed the oxygen-derived free radical removing agents DL-cysteine, methyl-methionine sulfonium bromide (MMSB), dimethyl sulfoxide (DMSO), and allopurinol to examine the role of oxyradicals in the mechanism of acute and chronic duodenal ulceration in the rat. These agents were administered by gavage under light ether anesthesia. All rats infused subcutaneously for 24 hr with pentagastrin (4 micrograms/kg/min) and carbachol (0.8 microgram/kg/min) developed acute duodenal ulceration and hyperchlorhydria (68 +/- 6.1 mumol vs 12.5 +/- 0.3 mumol, mean +/- SEM, N = 10, P less than 0.001). Pretreatment with DL-cysteine, MMSB, DMSO, or allopurinol provided dose-dependent protection against this ulceration without significantly influencing the hyperchlorhydria. One percent solutions of these agents protected at least 20% of rats against ulceration. Five or 10% solutions of DL-cysteine, MMSB, or DMSO protected at least 70% of rats against ulceration and similar concentrations of allopurinol protected all animals. All rats having intramuscular reserpine (0.1 mg/kg) every day for six weeks developed chronic duodenal ulceration and hyperchlorhydria (52 +/- 3.1 mumol vs 13.1 +/- 0.7 mumol, mean +/- SEM, N = 10, P less than 0.001). Pretreatment with DL-cysteine, MMSB, DMSO, or allopurinol achieved dose-dependent protection against ulceration without significantly influencing the hyperchlorhydria. One percent solutions of DL-cysteine, MMSB, or DMSO protected at least 60% of rats against ulceration; however, a similar concentration of allopurinol protected 80% of animals. Five or 10% solutions of DL-cysteine, MMSB, or DMSO protected at least 80% of rats against ulceration and similar concentrations of allopurinol protected all rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Sulphydryl-Containing Agents: A New Approach to the Problem of Refractory Peptic Ulceration

“…e.g. lysosomal enzymes, thereby leading to further tissue injury, besides caus ing degradation of hyaluronic acid, the princi pal component of the epithelial basement membrane, and cross-linking proteins, lipids and nucleic acids [14-16], These radicals were shown in experimental animals and in man to be implicated in the mechanism of peptic ulceration and removing them stimu lates the healing of this ulceration [7][8][9]13].…”

Effects of Zinc on Intestinal Injury and Some Serum Parameters in Ethanol-Administered Rats

“…7) Lipid peroxidation mediated by oxygen free radicals causes destruction and damage to cell membranes, and destroys the integrity of the duodenal mucosa. 3,37) In our study, the production of malondialdehyde as an index of lipid peroxidation was determined in intestinal tissues. Ethanol administration markedly elevated LPO levels in small intestine tissues with respect to the control animals.…”

“…37) Production of reactive oxygen species is a physiological process, but increase of it and dysbalance between the production of radicals and the antioxidant defense system can lead to oxidative stress. Acute or chronic ethanol administration increases lipid peroxidation of the cell membrane, and oxidative stress in several tissues.…”

The Relationship between Helicobacter Pylori and Oxygen-Derived Free Radicals in the Mechanism of Duodenal Ulceration.

“…It follows that an initial event of high magnitude adrenergic hypothalamovagal stimulation can result in a degree of mucosal ischaemia in the duodenum capable of yielding ulceration despite normochlorhydria (20)(21)(22). Free radicals were recently shownin the rat and in manto be implicated in peptic ulceration and scavenging them stimulates the healing of this ulceration (6)(7)(8)(9)(10). Helicobacter Pylori is found in the gastric antrum of more than 90% of patients with duodenal ulceration compared with only a minority of matched controls (1 1-15).…”

“…Recent experimental and clinical evidence suggests that oxygen-derived free radicals are directly responsible for the development of duodenal ulceration and that scavenging these radicals stimulates healing and prevents recurrence of ulceration (6)(7)(8)(9)(10). On the other hand, the pathogen Helicobacter Pylori has been implicated in the mechanism of peptic ulceration (ll-15) and infection with this bacterium triggers polymorphonuclear leukocyte and macrophage infiltration into its vicinity (16).…”