Abstract
Small intestinal injury is known to be one of the most commonly appearing pathologies, resulting in the use of medications such as: nonsteroidal anti-inflammatory drugs (NSAIDs), antitumor drugs and angiotensin-converting enzyme (ACE) inhibitors. The principal objective of this study is to evaluate the action of a novel mercaptoacrylic acid derivative able to release H2S on parameters of NO-synthase system and oxidative stress. Inducing enteropathy, three types of medications were used: indomethacin, an NSAID (35 mg/kg); methotrexate, an antitumor drug (10 mg/kg); and enalapril, an ACE inhibitor (2 mg/kg/day). 2-[(4-chlorophenyl-carbamoyl)-methyl]-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-acrylic acid (2C3DHTA) was introduced based on the background of medication-induced enteropathy (10 mg/kg/day). The survey showed that malondialdehyde (MDA) concentration, myeloperoxidase (MPO) activity, superoxide dismutase (SOD), catalase, and NO-synthases (NOS) were determined in the small intestinal mucosa. The increase in inducible NO-synthase (iNOS) activity was due to indomethacin and methotrexate administration. Constitutive NO-synthase (cNOS) activity was decreased by an ACE-inhibitor. The cytoprotective effect was demonstrated by 2C3DHTA, which returned iNOS activity to its control level and increased cNOS activity. The enterotoxic action of studied medication was accompanied by the development of oxidative stress manifested, activity of MPO was increased. MPO activity and manifestations of oxidative stress were decreased by 2C3DHTA. Effects of 2C3DHTA can be explained by the action of H2S, released from this compound in the gastrointestinal (GI) system.
Highlights
The development of various medical therapies has led to an increased frequency of medication side-effects [1]
Non-steroidal anti-inflammatory drugs (NSAIDs), antitumor drugs and hypotensive medications that inhibit the activity of angiotensin-converting enzyme (ACE) possess the highest enterotoxicity and influence the status of small intestinal microbiota [3]
In correspondence to the increase of nitric oxide (NO)-synthases activity, the concentration of NOx increased in the group of animals treated by 2A5DHT by 67%, p ≤ 0.01, and it did not change after 2C3DHTA
Summary
The development of various medical therapies has led to an increased frequency of medication side-effects [1]. Non-steroidal anti-inflammatory drugs (NSAIDs), antitumor drugs and hypotensive medications that inhibit the activity of angiotensin-converting enzyme (ACE) possess the highest enterotoxicity and influence the status of small intestinal microbiota [3]. L-Arginine is aand precursor foritNO synthesis to administration. L-Arginine is a precursor for NOand synthesis mammals. Of NO-synthases small intestinal mucosa a decrease of L-Arginineofconcentration in mucosa blood serum in led to a decreaseand of L-Arginine concentration in blood serumits inincreased indomethacinand metothrexate-treated indomethacinmetothrexate-treated rats, indicating utilisation for the synthesis of rats, indicating increased utilisation. For the synthesis of NO in the small intestine (Figure 5).
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