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Continued ingestion of plant secondary metabolites by ruminants can provoke pharmacological interactions with pharmaceutical agents used in animals. As some drugs and phytocompounds affect smooth muscle activity, the aim of this study was to verify the possible interaction between selected pharmaceutical agents and plant secondary metabolites towards bovine gastrointestinal motility. The interactions between phytocompounds—apigenin, quercetin, hederagenin, medicagenic acid—and medicines—erythromycin, flunixin meglumine and levamisole—were evaluated on bovine isolated abomasal and duodenal specimens obtained from routinely slaughtered cows. The obtained results confirmed the contractile effect of all three drugs used solely. Hederagenin and medicagenic acid (0.001 μM) enhanced the contractile effect of levamisole. Hederagenin additionally increased the impact of erythromycin. Both saponins (100 μM) showed synergistic effects with all tested pharmaceuticals. Apigenin and quercetin (0.001 μM) intensified the contractile response induced by erythromycin and levamisole. Moreover, both flavonoids (100 μM) showed an antagonistic interaction with all tested drugs which in that situation were devoid of the prokinetic effect. To conclude, plant metabolic metabolites such as saponins and flavonoids are potent modifiers of the effect of drugs towards gut motility. The synergy observed between phytocompounds and selected medicines can be beneficial in the treatment of cows with hypomotility disorders. [ABSTRACT FROM AUTHOR]

The application of pyriproxyfen (PPF) to drinking water and constant exposure of the whole population to this insecticide is an unprecedented action on a world scale and presents a new and serious challenge for toxicology. The aim of the study was to evaluate the potential effect of PPF on the intestine muscle activity. The experiments were performed on isolated duodenum and jejunum strips of rat, in isometric conditions. Doses of PPF in the range of 0.032-100 μM were used in the experiments. The obtained results indicate that PPF affected significantly the spontaneous activity of duodenum and jejunum strips, PPF caused the muscle relaxation when used in the concentration of 0.8 μM and higher. The reaction to acetylcholine (ACh) when PPF preceded or followed ACh application was also reduced. It is demonstrated that the reduction of the contraction caused by ACh was stronger when duodenum strips were preincubated in the presence of PPF solution than in case of ACh-precontracted strips. The first significant reaction of duodenal strips appeared in the presence of PPF in a dose of 0.16 μM and 0.8 μM when the insecticide application preceded and followed ACh treatment, respectively. Besides, the duodenum turned out to be much more susceptible to the tested insecticide than jejunum. Taking into account PPF kinetic data obtained in animals, the observed disturbances were caused by the insecticide used in relatively high concentrations. However, the full risk estimation requires the kinetic data obtained in human, especially from monitoring studies on general population after long-term exposure to PPF., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The coating of nanoparticles on materials for medical application [e.g., the coating of Fe3O4 nanopowder (IONP) with a carbon nanolayer] serves to protect and modify the selected biological, physical, and chemical properties of the coated material. Increases in chemical stability, changes in biocompatibility, and a modified surface structure are examples of the effects caused by the formation of carbon coatings. In the current study, Fe3O4 nanoparticles were coated with a carbon nanolayer (IONP@C) in a plasmochemical reactor (using radio-frequency plasma-enhanced chemical vapor deposition methods) under various experimental conditions. Based on data from X-ray diffraction, Raman, and IR spectroscopy, the best processing parameters were determined in order to produce a carbon coating that would not change the structure of the IONP. The materials with the best cover, i.e., a uniform carbon nanolayer, were used in cytotoxic tests to investigate their biological properties using the human HepG2 hepatocarcinoma cell line and chicken embryo red blood cells as an in vitro model. The obtained results proved the low cytotoxicity of Fe3O4 micropowder and IONP in contrast to IONP@C, which reduced cell viability, increased hemolysis, and generally was more toxic than bare Fe3O4.

The study was aimed at evaluating the effect of Roundup, polyoxyethylene tallow amine (POEA) and mixture of glyphosate and POEA in different levels on the motoric activity of jejunum strips. The incubation in the Roundup solutions caused a significant, mostly miorelaxant, reversible reaction of smooth muscle; only in the highest tested dose which is equivalent to the agricultural concentration (1% corresponding to 1.7g glyphosate/L) there was an irreversible disturbance of the spontaneous contractility and reactivity. The incubation in POEA solutions in the range of low doses (0.256; 1.28; 6.4mg/L) resulted in a biphasic muscle reaction (relaxation and contraction); whereas in the range of high doses, i.e. 32; 160 and 800mg/L (agricultural spray concentrations) induced only a miorelaxant, irreversible response. The results indicate very high toxicity of POEA which exceeds the toxicity of the commercial formulations. Besides, it is postulated that glyphosate and POEA may display antagonistic interaction towards the motoric activity of gastrointestinal tract., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Citrus flavonoids are acknowledged for numerous pharmacological activities, including the myorelaxant effect on various smooth muscles. However, there is no data on their effect on jejunum contractility. Therefore, the aim of the study at hand was to evaluate the impact of hesperetin and diosmetin along with their glycosides on the motoric activity of intestine and to verify the possible mechanism of hesperetin-induced effect. The experiments were performed on rat isolated jejunum strips and were conducted under isometric conditions. Hesperetin and diosmetin, but not hesperidin and diosmin, dose-dependently (10-100µM) and reversibly inhibited acetylcholine (1µM) and KCl (80mM) induced contractile activity. The antispasmodic effect of hesperetin was partially blocked by 4-aminopyridine (100µM), glibenclamide (100µM) and NG-nitro-L-arginine methyl ester (L-NAME, 100µM). By contrast, apamin (0.1µM), tetraethylammonium (500µM) and methylene blue (10µM) did not affect the magnitude of hesperetin-induced myorelaxant effect. Indomethacin (10µM) increased the force of hesperetin-evoked reaction. In conclusion, hesperetin and diosmetin are potent myorelaxant agents. The antispasmodic effect of hesperetin is partially mediated by fast current low-voltage activated K + channels, voltage-independent K+ channels and involves the nitric oxide pathway. Finally, hesperetin shows a synergistic effect with indomethacin towards jejunal KCl-precontracted smooth muscle., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Context: Plants of the genus Heracleum L. (Apiaceae) have a long history of being used in traditional medicines for the treatment of alimentary tract disorders, and these biological effects have been ascribed to the presence of furanocoumarins (including bergapten)., Objectives: This study aimed to develop an efficient, preparative, counter-current chromatographic separation of bergapten in order to characterize its spasmolytic activity in isolated rat jejunum strips., Materials and Methods: Successful separation of the dichloromethane extract of the fruits of Heracleum leskovii Grossh. was achieved by high-performance countercurrent chromatography (HPCCC) using a two-phase solvent system composed of n-heptane/EtOAc/MeOH/H2O (6:5:6:5, v/v/v/v). The pharmacological assessment of bergapten (0.0001-50 μM) on jejunum smooth muscle strips isolated from rats was conducted under isotonic conditions, following up to three hours of incubation., Results: The separation method was scaled up six-fold from analytical to semi-preparative conditions, affording bergapten of >99% purity in less than 30 min. This permitted bergapten to be available in quantity for spasmolytic tests on isolated jejunum strips from rats. Bergapten caused myorelaxation of the intestine preparations in the concentration range of 0.0001-1 μM. At higher doses, bergapten caused either relaxation or contraction of the smooth muscle., Discussion and Conclusion: Bergapten was successfully isolated by rapid HPCCC and its spasmolytic activity was confirmed, thereby providing a preliminary evidence base for the traditional medicine application. The data suggest that bergapten causes no irreversible changes to intestinal tissue.

Imperatorin, a psoralen-type furanocoumarin, is a potent myorelaxant agent acting as a calcium antagonist on vascular smooth muscle. Its effects on other types of smooth muscle remain unknown. Therefore, the aim of this study was to investigate the hypothesized myorelaxant effect of imperatorin on gut motor activity and, possibly, to define the underlying mechanism of action. Imperatorin was made available for pharmacological studies from the fruits of the widely available Angelica officinalis through the application of high-performance countercurrent chromatography (HPCCC). Imperatorin generated reversible relaxation of jejunum strips dose-dependently (1-100 μM). At 25 and 50 μM, imperatorin caused relaxation comparable to the strength of the reaction induced by isoproterenol (Isop) at 0.1 μM. The observed response resulted neither from the activation of soluble guanylate cyclase, nor from β-adrenoreceptor involvement, nor from Ca(2+)-activated potassium channels. Imperatorin relaxed intestine strips precontracted with high potassium concentration, attenuated the force and duration of K(+)-induced contractions, and modulated the response of jejunum strips to acetylcholine. The results suggest that imperatorin probably interacts with various Ca(2+) influx pathways in intestine smooth muscle. The types of some calcium channels involved in the activity of imperatorin will be examined in a subsequent study.

Glyphosate is an active substance of the most popular herbicides worldwide. Its common use results from the belief that it affects exclusively plants. However, studies on glyphosate and its trade formulations reveal that it causes numerous morphological, physiological and biochemical disturbances in cells and organisms of animals, including mammals. Due to the fact that shortly after oral exposure glyphosate is detected in the highest amount in small intestine, the aim of this study was to evaluate the effect of this compound on the spontaneous motoric activity of intestine under in vitro conditions. The experiments were conducted on rat jejunum strips under isotonic conditions. The strips were incubated in buffered (pH 7.35) and non-buffered (pH 5.2) glyphosate solutions ranged from 0.003 to 1.7 g/L. The results indicate that glyphosate applied in buffered solution affects significantly the spontaneous motoric activity of rat isolated jejunum strips. The muscle response is biphasic (miorelaxation accompanied by contraction). The contraction is observed already at a dose of 0.003 g/L and the first significant biphasic reaction at a dose of 0.014 g/L. The incubation of jejunum strips with glyphosate in non-buffered solution (pH 5.2) results in a different reaction. The smooth muscle undergoes only persistent relaxation, which is stronger than the response to glyphosate solution in pH 7.35. Motility disturbances are also observed after glyphosate removal from the incubation solution. The gathered data suggests that glyphosate impairs gastrointestinal strips' motility at concentration that are noticed in human exposed to non-toxic doses of glyphosate., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: The dry extract of Hedera helix leaves, due to its secretolytic and antispasmodic effects, is commonly used to produce pharmaceuticals applied in case of cough and other respiratory symptoms. The results of some in vitro studies as well as the clinical signs of poisoning caused by Hedera helix suggest however strong contractile effect on smooth muscle. In order to clarify the impact of α-hederin (the main active agent of ivy extract) on smooth muscle, the origin of activated calcium involved in α-hederin-induced contraction of gastric smooth muscle preparations was studied., Materials and Methods: The study was carried out on rat isolated stomach corpus and fundus strips, under isotonic conditions. The effect of α-hederin (100 μM) on smooth muscle preparations was measured before and after the treatment with verapamil during the incubation in modified Krebs-Henseleit solution (M K-HS). Besides, the effect of saponin was measured during the incubation of preparation in Ca2+-free modified Krebs-Henseleit solution or Ca2+-free EGTA-containing modified Krebs-Henseleit solution., Results: The obtained results revealed that the application of verapamil significantly inhibited the reaction evoked by α-hederin. The incubation of stomach strips in calcium-free modified Krebs-Henseleit solution did not change the force of the observed contraction in comparison to the reaction of the preparations incubated in regular incubation solution (M K-HS). In contrary, the replacement of M K-HS by calcium-free chelator-containing solution inhibited totally the reaction to α-hederin., Conclusions: The results indicated that α-hederin-induced contraction results from the influx of calcium which is located in intercellular spaces or bound to the outside of the cell membrane. The Ca2+ influx occurs predominantly through voltage-dependent calcium channels of L-type., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: The long tradition of using the dry extract of Hedera helix (common ivy) leaves in traditional and contemporary alternative medicine caused that many biological and pharmacological studies have been aimed at evaluating the effects of ivy. Some of the results suggest that Hedera helix extract possesses bronchodilatatory and antispasmodic activity. On the other hand, the symptoms of ivy intoxication in human and animals, as well as adverse-reactions observed during the therapy with ivy-based pharmaceuticals, indicate rather stimulant effect of the plant on smooth muscle. Thus, the aim of this study was to evaluate the effect of two main active substances extracted from the plant (α-hederin and hederacoside C) and the whole dry extract of Hedera helix on the gut motility., Materials and Methods: The experiments were carried out on isolated stomach corpus and fundus strips. The tissues were isolated from rats. The experiments were performed in isotonic conditions. The results are expressed as the percent of the reaction caused by a reference contractile substance, acetylcholine., Results and Conclusions: The obtained results revealed that α-hederin applied in the concentration ranged from 25 to 320μM significantly changed the spontaneous motoric activity of rat stomach smooth muscle. The observed reaction had always the same character, a contraction, and its force was concentration dependent. The second tested saponin, hederacoside C, did not alter the motility of rat isolated stomach corpus and fundus strips when administered in the concentration up to 100 μM, however, if applied in the concentration of 350 μM it induced a remarkable concentration of smooth muscle. Eventually, the whole extract of Hedera helix in a dose containing 60 μM of hederacoside C produced a strong contraction which strength was comparable with the reaction generated by acetylcholine. According to the results, it is very likely that α-hederin, but not hederacoside C contributes to the contractile response of isolated stomach corpus and fundus strips to the application of Hedera helix leaves' extract., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Experiments were performed on rat isolated gastrointestinal (GI) strips. The study was carried out in isotonic conditions during a long-term (5-8 h) incubation in modified Krebs-Henseleit solution, (M K-HS) at 37 degrees C. The reaction of GI muscle strips to acetylcholine (ACh) and histological images of the tissues strips were studied. Additionally, spontaneous motor activity of the jejunum strips was evaluated. The obtained results indicate that as well the spontaneous motility as the response of jejunum muscle strips to acetylcholine and the histological structure of the preparations changed throughout the incubation time. It suggests low time-stability of jejunum strips model during long-term experiment. In contrast, the response of stomach (corpus and fundus) strips to ACh application did not change significantly during 6 h incubation. Moreover, the histological structure of the stomach preparations was maintained unaffected for a long incubation time. Thus, the isolated stomach strips can be described as an alternative experimental model of high time-stability during long-term experiments.

Usually practicing veterinarians and animal keepers have to deal with inadequate supplementation of copper which causes deficiency diseases. However, instead of curing, the consequential intake of copper is likely to cause copper intoxication. Copper poisoning is observed particularly frequently, in sheep--the most sensitive domestic animal to copper toxicity. In most cases, sheep undergo chronic exposure to copper causing liver necrosis and resulting in massive haemolysis, haemoglobinuria and eventually in renal failure. The observed symptoms have an acute character and a set of them is called haemolytic crisis. The pathogenesis, signs and diagnosis of this syndrome are described in this article.