Lesions developing in the gastric mucosa of the rat after exposure to different gastric damaging agents (100 mg/kg aspirin, and 70% or 100% ethanol) were assessed by scanning electron microscopy. The severity of the lesions was quantified according to morphological criteria. Modifications in the severity of these lesions induced by pretreatment with zinc acexamate were also analyzed. The scanning electron microscope revealed that with the exception of absolute ethanol, which caused distinctive morphological features, lesions found under the different experimental agents shared a common pattern of progression. Ultrastructural lesions on surface epithelial cells preceded further alterations of parietal cells. After the integrity of the epithelial cells was lost, detachment of the parietal cells occurred, probably, through peptic digestion of the connections between cells and their extracellular matrices. Pretreatment of animals with zinc acexamate increased the presence of mucus on the gastric surface and significantly prevented the progression of lesions towards the severest stages. Ultrastructural damage of surface epithelial cells was not influenced by this treatment, but detachment of damaged cells was clearly diminished. These data confirm the protective effect of zinc acexamate against gastric aggressions. Moreover, our studies confirm the notion that mucus secretion and maintenance of continuity on the gastric lumen by surface epithelial cells is of critical importance in preventing the gastric damage induced in these experimental models.
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Hepatol Commun
November 2024
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain.
Biomed Pharmacother
September 2018
Department of physiology, Unité de Biologie et anthropologie moléculaires appliquées au développement et à la santé, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia. Electronic address:
Aim: Zinc has proved its efficacy in many models of ischemia reperfusion (I/R) injury. In this study, we used zinc acexamate (ZAC) as an exogenous source of zinc against renal I/R injury and we investigated whether its protective effects are mediated by the decrease of oxidative stress, inflammation, and mitochondria induced-apoptosis.
Methods: Rats were orally pretreated with vehicle or ZAC (10 or 100 mg/kg) 24 h and 30 min prior to 1 h of bilateral renal warm ischemia and 2 h of reperfusion.
Toxicol Res
September 2013
College of Pharmacy, Dankook University, Cheonan, Korea ; Life Science Pharmaceutical Research Center, Dankook University, Cheonan, Korea.
A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of ε-acetamidocaproic acid (AACA), the primary metabolite of zinc acexamate (ZAC), in rat plasma by using normetanephrine as an internal standard. Sample preparation involved protein precipitation using methanol. Separation was achieved on a Gemini-NX C18 column (150 mm × 2.
View Article and Find Full Text PDFJ Pharm Pharmacol
October 2012
College of Pharmacy, Dongguk University-Seoul College of Pharmacy, Seoul National University, Seoul, Korea.
Objectives: Anti-ulcer drugs are frequently used in patients with acute renal failure (ARF). Zinc acexamate is ionized to zinc and ε-acetamidocaproic acid and free EACA exerts a potent therapeutic effect in treating gastric or duodenal ulcers with few side effects. Thus, pharmacokinetic changes in rats with acute renal failure induced by uranyl nitrate (U-ARF rats) were investigated in this study.
View Article and Find Full Text PDFXenobiotica
March 2012
College of Pharmacy, Ewha Womans University, Seoul, South Korea.
The pharmacokinetics of ϵ-acetamidocaproic acid (AACA) were evaluated after the intravenous and oral administration of an antiulcer agent, zinc acexamate (ZAC) at a dose of 20 mg kg⁻¹ (ion pairing between zinc and AACA) in rats with indomethacin-induced acute gastric ulcer (IAGU) or indomethacin-induced small bowel inflammation (ISBI). In IAGU rats, the area under the curves (AUCs) of AACA were significantly smaller after both the intravenous (551 versus 1270 μg min ml⁻¹) and oral (397 versus 562 μg min ml⁻¹) administration of ZAC than controls, possible due to the significantly faster CL(R) of AACA. In ISBI rats, however, the AUCs of AACA were comparable with controls after both the intravenous and oral administration of ZAC.
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