MECHANISMS OF CHANGES IN THE CONTRACTILE ACTIVITY OF SMOOTH MUSCLES OF THE GASTROINTESTINAL TRACT OF RATS UNDER PROLONGED ORAL EXPOSURE TO A MIXTURE OF POLYPROPYLENE NANO- AND MICROPARTICLES

Maria Shulha, Oleksandr Chunikhin, Ivan Voiteshenko, Andrij Sybirnyy, Tamara Davydovska, Serhii Bunak, Volodymyr Bondar, Khrystyna Sholota, Yurii Slinchenko, Olga Tsymbalyuk


DOI: http://dx.doi.org/10.30970/sbi.2003.903

Abstract


Background. Polypropylene ranks first in terms of world production among primary plastics. It is known that with prolonged intake into the body, polypropylene particles cause an increase in the total level of pro-inflammatory cytokines, lead to inflammation of the intestinal tissue and disruption of the intestinal barrier. In previous experiments, we showed that prolonged oral administration of a suspension of polypropylene particles causes changes in the frequency and strength of spontaneous contractions of the smooth muscles of the stomach and large intestine of rats. The aim of this work was to investigate the contractions of smooth muscles of the antrum and caecum induced by the activation of voltage-gated Са2+-channels, muscarinic and nicotinic acetylcholine receptors, as well as the release of Са2+ ions from intracellular stores during long-term oral consumption of polypropylene.
Materials and Methods. The experiments were conducted on female Wistar rats. The suspension of polypropylene particles was prepared from disposable dishes according to the Roursgaard method with minor modifications. The experimental group animals received a suspension of a mixture of polypropylene nano- and microparticles (with an average hydrodynamic diameter of 1.4 µm) in drinking water (at a dose of 2.5 mg/kg daily) for 6 weeks. The contractile activity of the preparations of the circular smooth muscles of the antrum and caecum was activated by: high-potassium solution (80 mM), the agonist of muscarinic cholinergic receptors acetylcholine (10-5 M), the activator of the L-type voltage-gated Са2+-channels BayK 8644 (10-6 M), the agonist of nicotinic cholinergic receptors nicotine (10-4 M), and the activator of ryanodine-sensitive Ca2+-channels of the sarcoplasmic reticulum caffeine (0.02 M). Contractile activity was recorded in isometric mode and analyzed by the method of Kosterin–Burdyga mechanokinetic analysis with the calculation of normalized maximum velocities of the contraction (Vnc) and relaxation (Vnr) phases.
Results. It was found that with prolonged oral intake of polypropylene particles, there is a significant increase in the amplitude of contractions of the antrum and caecum, activated by high-potassium solution and BayK 8644, due to increased influx of Ca2+ ions into myocytes through L-type voltage-gated Са2+-channels. Also, under these conditions, an increase in contractions of the antrum and caecum, activated by acetylcholine and nicotine, is observed due to increased cholinergic neurotransmission both at the level of enteric neurons and smooth muscle cells. With prolonged exposure to polypropylene particles, a significant increase in caffeine-induced contractions of both types of muscles is observed, caused by the release of Ca2+ ions from the sarcoplasmic reticulum. In the case of various contraction inducers, a significant decrease in the normalized maximum velocity of the relaxation phase was observed, likely due to a decrease in the efficiency of Ca2+ ion extrusion from myocytes.
Conclusions. Long-term oral administration of polypropylene particles induces a significant increase in contractile responses of the circular smooth muscles of the stomach and large intestine, caused by the pathways of electro- and pharmaco-mechanical excitation-contraction coupling and the release of excitatory neurotransmitters from enteric neurons, and also probably inhibits the systems of active pumping of Ca2+ ions from myocytes.


Keywords


mixture of nano- and microplastics, polypropylene, smooth muscles, gastrointestinal tract, voltage-gated Са2+-channels, cholinergic transmission, ryanodine receptors, contraction, mechanokinetic analysis

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