Changes of nitric oxide system and lipid peroxidation parameters in the digestive system of rats under conditions of acute stress, and use of nonsteroidal anti-inflammatory drugs

Abstract

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with being physiologically stressed often occurs in in the course of different pathologies. This situation may result in the alteration of digestive system functioning. The effect of stress brings about changes in the activity of nitric oxide synthase (NOS), arginase, cyclooxygenase (COX) and lipid peroxidation, whereas the use of NSAIDs interrupts the multiple functions of the cell via the inhibition of prostaglandins (PGs) synthesis. Taking into account that NOS and COX-systems are connected in their regulation, the aim of the study was to determine the role played by NOS and lipid peroxidation under conditions of the combined action of NSAIDs and stress. In our study, male rats were used. The NSAIDs (naproxen - a non-selective COX inhibitor, celecoxib - a selective COX-2 blocker, and the compound 2A5DHT (which is the active substance of dual COX, and the lipoxygenase (LOX) inhibitor, darbufelone) were all administered at a dose 10 mg/kg, prior to water restraint stress (WRS). WRS brought about an increase of inducible NOS (iNOS) activity in the intestinal mucosal and muscular membranes, as well as in the pancreas. Because of this, constitutive NOS izoform (cNOS) and arginase activities decreased. Moreover, the MDA concentration increased, indicating the development of oxidative stress. In our work, pretreatment with naproxen, as in the WRS model, engendered a decrease in iNOS activity. What is more, administration of Celecoxib did not change iNOS activity, as compared to WRS alone, and it showed a tendency to reduce lipid peroxidation. In addition, 2A5DHT prior WRS brought about a decrease of iNOS activity, with the subsequent rise of cNOS activity. Of note, MDA concentration decreased in all studied organs, indicating the reduction of lipid peroxidation under the action of the darbufelone active substance.

Hydrogen Sulfide Releasing 2-Mercaptoacrylic Acid-Based Derivative Possesses Cytoprotective Activity in a Small Intestine of Rats with Medication-Induced Enteropathy

“…In our study, a novel 2-mercaptoacrylic acid-based derivative—2C3DHTA—was used. This compound was synthesized on the basis of its parent compound 2-amino-5-(3,5-ditertbutyl-4-hydroxybenzylidene)-thiazol-4-one (2A5DHT), which is an active substance of a well known dual COX/LOX inhibitor darbufelone [ 14 , 15 , 34 ]. In a randomized, double blind, rising single-and multiple-dose study in healthy volunteers, it was shown that darbufelone was well tolerated up to the oral daily dose of 100 mg and demonstrated anti-inflammatory effects [ 14 ].…”

“…Dual COX/LOX inhibitors constitute a valuable alternative to classical NSAIDs and selective COX-2 inhibitors for the treatment of inflammatory diseases. Moreover, they appear to be almost exempted from gastrointestinal toxicity [ 15 , 34 ]. Chemical insertion of a H 2 S-donating moiety into establishing a parent compound resulted in its new properties.…”

Synthesis of indoline-thiazolidinone hybrids with antibacterial and antifungal activities

“…Among the design strategies in drug discovery, considerable interest has been paid to thiazole-based heterocycles [3][4][5]. Thiazole/thiazolidinone derivatives constitute an important class of therapeutic agents in medicinal chemistry including antitrypanosomal [6], antiviral [7,8], anticancer [9][10][11], antioxidant [12,13], anti-inflammatory [14][15][16] activities and also display a pivotal role as antimicrobial and antifungal agents [17,18]. Thus, a thiazole ring is present in several drugs, such as penicillin, monobactam, sulfathiazole, thiabendazole and nizatidine, making this heterocyclic fragment ideal for construction more potent and safer drug candidates, especially in the therapy of infectious diseases (Fig.…”

Oxidative/antioxidant balance and matrix metalloproteinases level in the knee cartilage of rats under experimental osteoarthritis and probiotic administration

“…The state of the microbiome is also closely related to the pathogenesis of some metabolic and inflammatory diseases, that may involve in the development of OA. Factors such as stress, use of medication such as nonsteroidal anti-inflammatory drugs may lead to the formation of oxidative stress in intestines and have been found to contribute to intestinal dysbiosis [7]. Therefore, the study of the mechanisms that link the participation of intestinal microflora in the development of joint diseases becomes urgent.…”