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

Abstract

Background: A particularly pressing problem is determining consumer-safe doses of potentially health- and life-threatening substances, such as acrylamide. The aim of the study was to determine how acrylamide affects the pituitary adenylate cyclase-activating polypeptide (PACAP)-immunoreactive intramural neurons in the small intestine of sexually immature gilts. Methods: The study was conducted on 15 sexually immature Danish gilts receiving for 28 days empty gelatin capsules or acrylamide in low (0.5 µg/kg of body weight (b.w.)/day) and high (5 µg/kg b.w./day) doses. After euthanasia, intestinal sections were stained using the double immunofluorescence staining procedure. Results: Studies have shown that oral administration of acrylamide in both doses induced a response of intramural neurons expressed as an increase in the population of PACAP-immunoreactive neurons in the small intestine. In the duodenum, only in the myenteric plexus (MP) was an increase in the number of PACAP-immunoreactive (IR) neurons observed in both experimental groups, while in the outer submucous plexus (OSP) and inner submucous plexus (ISP), an increase was noted only in the high-dose group. In the jejunum, both doses of acrylamide led to an increase in the population of PACAP-IR neurons in each enteric plexus (MP, OSP, ISP), while in the ileum, only supplementation with the higher dose of acrylamide increased the number of PACAP-IR enteric neurons in the MP, OSP, and ISP. Conclusions: The obtained results suggest the participation of PACAP in acrylamide-induced plasticity of enteric neurons, which may be an important line of defence from the harmful action of acrylamide on the small intestines.

Dietary Exposure to Acrylamide Has Negative Effects on the Gastrointestinal Tract: A Review

“…In turn, in myenteric plexuses, ACR at a low dose increased the number of GAL-, nNOS-, and VIP-immunoreactive (IR) neurons in the cardia, corpus, and pylorus; VAChT-and SP-IR in the corpus and pylorus; and in the case of CART, the changes were significant only in the corpus and CGRP only in the pylorus. However, in all examined sections of the stomach (cardia, corpus, pylorus), an increase in the number of myenteric plexuses neurons immunopositive for all tested neuroactive substances (GAL, CART, VAChT, VIP, SP, CGRP, nNOS) was noted [89][90][91][92].…”

“…High dose: an increased population of PACAP-, CART-, CGRP-, VAChT-, VIP-, nNOS-, GAL-, and SP-immunoreactive neurons in the MP, OSP and ISP. [86,[92][93][94] jejunum pig 0.5 and 5 µg/kg of b.w./day for 28 days Low dose: increased immunoreactivity with respect to PACAP, CART, CGRP, VAChT, GAL, and SP in the MP; an increased number of PACAP-immunoreactive neurons in the OSP; an increase in the number of PACAP-, VIP-, and GAL-immunoreactive and a decrease in the nNOS-positive neurons in the ISP. High dose: an increase in the population of PA-CAP-, CART-, CGRP-, VAChT-, VIP-, GAL-, and SP-immunoreactive and a decrease in that of nNOS-positive neurons in the MP, OSP, and ISP.…”

“…High dose: an increase in the population of PA-CAP-, CART-, CGRP-, VAChT-, VIP-, GAL-, and SP-immunoreactive and a decrease in that of nNOS-positive neurons in the MP, OSP, and ISP. [86,[92][93][94][95] ileum pig 0.5 and 5 µg/kg of b.w./day for 28 days Low dose: an increase in the number of CART-, CGRP-, VIP-, GAL-, and SP-immunopositive and a decrease in the number of nNOS-positive in the MP; an increase in immunoreactivity with respect to VAChT, VIP, and SP and a decrease in the number of nNOS-immunoreactive neurons in the OSP; increased number of CGRP-, VAChT-, VIP-, and GAL-immunoreactive neurons the ISP. High dose: an increase in the number of PACAP-, CART-, CGRP-, VAChT-, VIP-, GAL-, and SP-immunoreactive and decreased the number of nNOSpositive neurons in the MP, OSP, and ISP.…”

“…High dose: an increase in the number of PACAP-, CART-, CGRP-, VAChT-, VIP-, GAL-, and SP-immunoreactive and decreased the number of nNOSpositive neurons in the MP, OSP, and ISP. [39,86,[92][93][94] Neuroactive substances: CART-cocaine-and amphetamine-regulated transcript peptide, CGRPcalcitonin gene-related peptide, GAL-galanin, nNOS-neuronal nitric oxide synthase, NPY-neuropeptide Y, PACAP-pituitary adenylate cyclase-activating polypeptide, VIP-vasoactive intestinal polypeptide, VAChT-vesicular acetylcholine transporter. Enteric plexuses: MP-myenteric plexus, OSP-outer submucous plexus, ISP-inner submucous plexus.…”

“…Further studies with a domestic pig model showed that a 4-week supplementation of ACR considerably altered the chemical coding of ENS neurons. The changes depended on the dose and the gastrointestinal tract section under investigation [39,86,[89][90][91][92][93][94][95]. In the stomach, low-dose ACR supplementation corresponding to a tolerable daily intake (TDI) (0.5 µg/kg b.w./day) caused an increase in the population of neurons immunoreactive to galanin (GAL), cocaine-and amphetamine-regulated transcript peptide (CART), vesicular acetylcholine transporter (VAChT), VIP, and SP in submucous plexuses in the corpus.…”