Alpha-Lipoic Acid Improves Acetic Acid-Induced Gastric Ulcer Healing in Rats
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Alpha-Lipoic Acid Improves Acetic Acid-Induced Gastric Ulcer Healing in Rats Berna Karakoyun,1,6 Meral Yüksel,2 Feriha Ercan,3 Can Erzik,4 and Berrak Ç. Yeğen5
Abstract—To evaluate the role of ALA treatment on the healing of acetic acid-induced gastric ulcer, rats were given ALA (35 mg/kg/day) or saline for 3 days before the induction of ulcer and the treatment was continued twice daily for 2 days (early) or 10 days (late) until they were decapitated. Gastric ulcer index, microscopic score, elevated DNA fragmentation and chemiluminescence levels of the saline-treated ulcer groups were all reduced by ALA treatment. Likewise, ALA treatment inhibited chemiluminescence levels in both early and late ulcer groups. Marked reduction in glutathione levels of the saline-treated early ulcer group was reversed by ALA treatment, while ALA treatment was effective in depressing gastric myeloperoxidase activity in the late ulcer group. In conclusion, ALA treatment shows protective role in the healing of acetic acid-induced gastric injury in rats via the suppression of neutrophil accumulation, preservation of endogenous glutathione, inhibition of reactive oxidant generation and apoptosis. KEY WORDS: alpha-lipoic acid; ulcer healing; acetic acid; oxidant damage; apoptosis.
cells, and submucosal acid sensors, prostaglandins, cytokines, enteric nerves and blood flow [2]. Disturbing the balance between aggressive and protective factors that control cell apoptosis and proliferation leads to gastric ulceration, which then activates the repairing system in the gastric mucosa. Gastric ulcer healing, which involves cell migration, proliferation, epithelial regeneration, angiogenesis, and matrix deposition, is largely coordinated by a variety of growth factors, transcription factors and cytokines [3–5]. Among many experimental ulcer models, acetic acid ulcer model is more commonly used to conduct pathophysiological and pharmacological studies on peptic ulcers. This chronic ulcer model, which highly resembles human ulcers in terms of both pathological features and healing mechanisms, is utilized to develop new anti-ulcer drugs that could potentially prevent ulcer relapse or enhance ulcer healing [6, 7]. Alpha-lipoic acid (ALA), an endogenous agent found in a variety of meats, notably kidneys, heart and liver, as well as in spinach, broccoli and potatoes, has been widely used as a dietary supplement [8]. This natural compound, chemically named as 1,2-dithiolane-
INTRODUCTION The pathogenesis of gastric ulcer is based on a multifactorial and complex interaction between so-called protective and aggressive factors, including mucosal integrity, secretion of gastric acid and pepsin, gastroduodenal motility, Helicobacter pylori and use of nicotine and non-steroidal anti-inflammatory drugs [1]. The mucosal barrier consists of a pre-epithelial mucus layer, intercellular tight junctions connecting the epithelial 1
Physiology, Health Sciences Faculty, Department of Nursing, Marmara University, Haydarpaşa 34668, İstanbul, Turkey 2 Vocational School of He
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