Effect of NSAIDs Supplementation on the PACAP-, SP- and GAL-Immunoreactive Neurons in the Porcine Jejunum

Abstract

Side effects associated with nonsteroidal anti-inflammatory drugs (NSAIDs) treatment are a serious limitation of their use in anti-inflammatory therapy. The negative effects of taking NSAIDs include abdominal pain, indigestion nausea as well as serious complications such as bleeding and perforation. The enteric nervous system is involved in regulation of gastrointestinal functions through the release of neurotransmitters. The present study was designed to determine, for the first time, the changes in pituitary adenylate cyclase-activating polypeptide (PACAP), substance P (SP) and galanin (GAL) expression in porcine jejunum after long-term treatment with aspirin, indomethacin and naproxen. The study was performed on 16 immature pigs. The animals were randomly divided into four experimental groups: control, aspirin, indomethacin and naproxen. Control animals were given empty gelatin capsules, while animals in the test groups received selected NSAIDs for 28 days. Next, animals from each group were euthanized. Frozen sections were prepared from collected jejunum and subjected to double immunofluorescence staining. NSAIDs supplementation caused a significant increase in the population of PACAP-, SP- and GAL-containing enteric neurons in the porcine jejunum. Our results suggest the participation of the selected neurotransmitters in regulatory processes of the gastrointestinal function and may indicate the direct toxic effect of NSAIDs on the ENS neurons.

Glyphosate-induced changes in the expression of galanin and GALR1, GALR2 and GALR3 receptors in the porcine small intestine wall

“…Inflammatory processes in the intestines, such as proliferative enteropathy 33 , Brachyspira hyodysenterieae infection 11 , experimentally and naturally induced colitis 12 , or gastric ulcers 10 , had a considerable impact on the GAL level and increased its expression. Likewise, long-term NSAID (aspirin, naproxen and indometacin) supplementation increased GAL expression in all intestinal ganglia in pig duodenum and jejunum 34 , 35 . The same effect was observed as a result of pig intoxication with bisphenol A 13 and acrylamide 7 .…”

Acrylamide-Induced Changes in the Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Immunoreactivity in Small Intestinal Intramural Neurons in Pigs

“…Changes in the PACAP-positive neuron population in the ENS plexuses in the duodenum and jejunum regions of the pig have been described as an effect of the use of non-steroidal anti-inflammatory drugs (NSAIDs). Following naproxen, indomethacin, and aspirin supplementation, an increase in the number of PACAP-IR neurons in all three types of ENS plexuses (MP, OSP, ISP) was observed [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. Similarly, an increase in the number of PACAP-positive neurons in the submucosal ganglion was observed in the course of gastric hyperacidity induced by hydrochloric acid infusion [ 44 ].…”

1D and 2D Coordination Polymers of Calcium with Nonsteroidal Anti‐Inflammatory Drugs: Synthesis, Crystal Structures, Hirshfeld Surfaces, Antimicrobial and Antioxidant Activities

“…Moreover, NSAIDs are active against several tumors. Their activity is attributed to mitochondrial dysfunction, [26] free radical scavenging [27,28] and apoptosis of programmed cell death. [17,26,29] Furthermore, they were primary drugs to control inflammation and pain relief during the ongoing coronavirus pandemic.…”

“…[30] Unfortunately, long-term NSAID therapies can lead to severe adverse effects like abdominal pains, indigestion, nausea and serious complications from the gastrointestinal tract such as bleeding and perforation. [10,27,31] The therapeutic value of organic drugs may be improved by their complexation with properly selected metal cations. Imerging interactions enhance bioactivity and bioavailability of those substances.…”

“…Furthermore, they were primary drugs to control inflammation and pain relief during the ongoing coronavirus pandemic [30] . Unfortunately, long‐term NSAID therapies can lead to severe adverse effects like abdominal pains, indigestion, nausea and serious complications from the gastrointestinal tract such as bleeding and perforation [10,27,31] …”