A New Participant in the Pathogenesis of Alcoholic Gastritis: Pyroptosis

Abstract

Background/Aims: Alcohol abuse exerts deleterious effects on the internal organs of the body, and alcohol-related gastritis is a common disease for which prompt treatment is essential to prevent the condition from growing worse. However, the therapeutic methods have some adverse effects. Determining the pathogenic mechanisms of alcoholic gastritis is therefore essential. Methods: The MTT assay was developed in order to determine the optimal concentration of alcohol needed to treat gastric mucosal cells. The effects of alcohol on the gastric mucosal cells were determined by qRT-PCR and western blot. The release of IL-1β and IL-18 were determined by ELISA assay. The immunofluorescence assay was used to detect caspase-1 activation levels, while immunohistochemical assay and HE staining were performed to identify the effectiveness of the caspase-1 inhibitor on alcoholic gastritis. The TUNEL assay was used to determine DNA fragmentation. Results: Here, we clarified that ethanol treatment could cause cell DNA damage, activate caspase-1, and promote the generation and release of IL-1β and IL-18. In other words, ethanol could induce pyroptosis. Interestingly, a caspase-1 inhibitor could significantly suppress pyroptosis, decrease the release of inflammatory cytokines induced by ethanol, and cause no side effects in vivo and in vitro. Conclusion: Collectively, our results showed that pyroptosis is involved in the pathogenesis of alcohol-induced gastritis and that caspase-1 inhibitor Ac-yvad-cmk could effectively decrease the damage caused by alcohol, making it a potentially promising agent for the treatment of alcoholic gastritis.

Lactobacillus reuteri DSM 17938 Protects against Gastric Damage Induced by Ethanol Administration in Mice: Role of TRPV1/Substance P Axis

“…Excessive alcohol consumption is an important public health problem, and globally, alcohol ingestion in 2016 was estimated to be 6.4 L of pure alcohol per person, which is related to risk of developing of several diseases, resulting in some 3 million deaths [1]. High ethanol concentrations present in alcoholic beverages have the capacity to directly injure the mucosa of the gastrointestinal tract, resulting in acute and chronic damage, such as erosive hemorrhagic gastritis and peptic ulcers [2,3,4]. Since ethanol is one of the most usually accepted and abused psychoactive drugs [1], the gastric injury generated by its abuse is a worrying consequence.…”

Preventive and Regenerative Effect of Glutamine and Probiotics on Gastric Mucosa in an Experimental Model of Alcohol-Induced Injury in Male Holtzman Rats

“…The cause of gastritis may be related to smoking, alcohol consumption and/or the use of non-steroidal anti-inflammatory drugs (NSAIDs) or steroids [2]. Long-term alcohol abuse may cause acute erosive hemorrhagic gastritis, upset stomach, and chronic atrophic gastritis [3,4]. Alcohol is able to activate cellular responses and increases reactive oxygen species (ROS), which is a cytotoxic agent of the stomach mucosa [5].…”

Alcohol-Induced Neuropathy in Chronic Alcoholism: Causes, Pathophysiology, Diagnosis, and Treatment Options

“…Excessive alcohol consumption leads to the severe failures of digestive, cardiovascular, and nervous (central and peripheral) systems [6][7][8][9][10]. The most frequent disorders related to alcohol abuse include alcoholic liver disease (including steatosis, steatohepatitis, cirrhosis, or hepatocellular carcinoma), pancreatitis, gastritis, hypertension, arrhythmia, or cardiomyopathy [11][12][13][14][15][16][17][18][19][20][21]. The prevalence of the alcoholic liver disease among heavy drinkers is estimated at 15-30% [22].…”

“…Alcohol-induced neuropathy, also known as alcoholrelated peripheral neuropathy (ALN), is a toxic polyneuropathy that leads to the damage of sensory, motor, and autonomic nerve fibers leading to the thinning of the myelin sheaths and further impairments of neural functions [14,49]. ALN is characterized by spontaneous burning pain, hyperalgesia, and allodynia.…”