The Influence of High and Low Doses of Bisphenol A (BPA) on the Enteric Nervous System of the Porcine Ileum

Abstract

Bisphenol A, used in the production of plastic, is able to leach from containers into food and cause multidirectional adverse effects in living organisms, including neurodegeneration and metabolic disorders. Knowledge of the impact of BPA on enteric neurons is practically non-existent. The destination of this study was to investigate the influence of BPA at a specific dose (0.05 mg/kg body weight/day) and at a dose ten times higher (0.5 mg/kg body weight/day), given for 28 days, on the porcine ileum. The influence of BPA on enteric neuron immunoreactive to selected neuronal active substances, including substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL), vesicular acetylcholine transporter (VAChT-used here as a marker of cholinergic neurons), and cocaine-and amphetamine-regulated transcript peptide (CART), was studied by the double immunofluorescence method. Both doses of BPA affected the neurochemical characterization of the enteric neurons. The observed changes depended on the type of enteric plexus but were generally characterized by an increase in the number of cells immunoreactive to the particular substances. More visible fluctuations were observed after treatment with higher doses of BPA. The results confirm that even low doses of BPA may influence the neurochemical characterization of the enteric neurons and are not neutral for living organisms.

Neurochemical characterization of the enteric neurons within the porcine jejunum in physiological conditions and under the influence of bisphenol A (BPA)

“…33 The results obtained in the present study are very interesting and show that the human and the porcine nervous systems (especially the ENS) are similar with regard to electrophysiological, biochemical, and neurochemical organization, 23,34 and the domestic pig is being increasingly used as an animal model of processes taking place in the human body. 4,35 Therefore, the observations made in the present investigation may be the first step to a better understanding of the mechanisms connected with the impact of BPA on the human intestine.…”

“…Namely, BPA acts on the mast cells, causing an increase in the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, interferon-gamma (INF-γ), IL-4, histamine, and many other factors, 40,48,49 but the kind of immune factors released during exposure to BPA clearly depends on animal species and the toxin dose. 4,49 Moreover, it is known that BPA affects macrophages, which contributes to the increase in the synthesis of TNF-α and IL-6 with a simultaneous decrease in the production of IL-10 and transforming growth factor (TGF)-β. 48 The pro-inflammatory action of BPA also concerns the GI tract, in which the administration of this substance resulted in an increase in the number of eosinophils and neutrophils and intensification of the TNF-α, IL-1α and IL-1β synthesis.…”

“…First of all, this substance acts on the nervous and reproductive systems. 4,6,7 It is known that the neurotoxic effects of BPA consist in abnormalities in the development of dendrites and axons of neuronal cells 8 and changes in synaptogenesis. 9 Moreover, even short exposure to BPA may result in disorders in higher neural activity, including learning, cognition, and memorizing, which may occur a long time after intoxication.…”

“…The ENS is the part of the autonomic nervous system, which is located in the wall of the GI tract and is characterized by significant independence from the brain. 4,22 The essential characteristic of the ENS is the special differentiation of neuronal cells with respect to morphology, physiology, electrophysiological properties, and neurochemical characterization. 23 Enteric neurons are grouped into intramural ganglionated plexuses interconnected with a dense network of nerve fibers and the number and types of these plexuses depend on the animal species and fragment of the digestive tract.…”

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration

“…The in vivo experiments have demonstrated that BPA disrupts enteric innervation within particular parts of the porcine small intestine [11,12].…”