N-acetylcysteine a possible protector against indomethacin-induced peptic ulcer: crosstalk between antioxidant, anti-inflammatory, and antiapoptotic mechanisms

Abstract

This study investigated the gastroprotective effects of N-acetylcysteine (NAC) against indomethacin-induced gastric ulcer in rats. Ulceration was induced by a single oral administration of indomethacin (30 mg/kg). 50 male albino rats were allocated into 5 equal groups: control group received normal saline orally, indomethacin group rats received normal saline orally for 5 days and indomethacin (50 mg/kg) on the last day, ranitidine group received ranitidine (reference drug) orally for 5 days (50 mg/kg) before receiving indomethacin (50 mg/kg) on the last day, and NAC groups received NAC orally at 300 and 500 mg/kg, respectively, for 5 days before receiving indomethacin (50 mg/kg) on the last day. Gastric tissue interleukin-1β (IL-1β), interferon-γ (IFN-γ), and caspase-3 levels were immunoassayed. Total thiol (T-SH), myeloperoxidase (MPO), and glucose-6-phosphate dehydrogenase (G6PD) were determined by spectrophotometry. Cytokine-induced neutrophil chemoattractant 2α (CINC-2α) gene expression was evaluated in addition to Bcl-2 immunohistochemistry. Pretreatment with NAC improved the inflammatory, apoptotic, and redox status in a dose-dependent manner particularly in NAC 500 mg/kg pretreated group. These results show a role for NAC in improving indomethacin-induced gastric ulceration via antioxidative, antiapoptotic, and anti-inflammatory interactive mechanisms.

Gastroprotective Effect of Vanillin on Indomethacin-Induced Gastric Ulcer in Rats: Protective Pathways and Anti-Secretory Mechanism

“…Then phenolphthalein was added as an indicator and continues titrating until red color reappears however the total volume of alkali added indicated total acidity as we described before [4]. Moreover, pH of gastric juice was determined by digital pH meter.…”

“…However it provokes aggressive ulcerogenic potential in both animals and humans [2]. Many previous studies tried to decrease damaging indomethacin effect on gastrointestinal mucosa [3][4][5].…”

Gastroprotective Effect of Punicalagin against Ethanol-Induced Gastric Ulcer: The Possible Underlying Mechanisms

“…Subsequently phenolphthalein was added as an indicator and continues titrating until red colour reappeared however the total volume of alkali added indicated total acidity as we described before [14].…”

“…Gastric tissue samples were fixed in buffered 10% formalin and processed for histopathological examination as we described before [14]. Briefly, five micrometre-thick paraffin sections were prepared and stained with haematoxylin and eosin for light microscope examination (magnification × 20) by double blind pathologist.…”

“…Animals were randomly divided into three experimental series, each consisting of 4 groups (n=6); first group act as normal control received vehicle orally by intra-gastric gavage, second group administered of 5 ml/kg of absolute ethanol orally [13], third group (Ran+ Ethanol): Rats received ranitidine (Ran) (used as a standard reference drug) orally (50 mg/kg) [14] 2 h before the administration of ethanol and group 4 (PCG +Ethanol): Treated with Punicalagin (PCG) orally (4 mg/kg) [15] for 2 h before the administration of ethanol. All animals were fasted 24 h prior to ethanol administration except for water to exclude exogenous dietary effect.…”