[Plant-derived contaminants in food : Occurrence, effects and risk assessment]. / Pflanzliche Kontaminanten in Lebensmitteln : Vorkommen, Wirkung und Risikobewertung.

Among the various contaminants, the group of natural plant-derived substances in the modern food chain has been generating increasing concern in recent years. The adverse effects encountered may be diverse and pose risks of acute, subchronic or chronic toxicity. The underlying mechanisms of toxicity may be thresholded or be based on interactions with DNA, as for genotoxic carcinogens, for which the existence of a threshold cannot be assumed. This article gives an overview of the major plant-derived contaminants of present concern in the modern food chain and describes their mode of action and adverse effects.

Improving the food safety of bakery products by simultaneously monitoring the occurrence of pyrrolizidine, tropane and opium alkaloids.

The exponential number of food alerts about concerning levels of some plant-alkaloids, such as pyrrolizidine, tropane and opium alkaloids, have stressed the need to monitor their occurrence in foods to avoid toxic health effects derived from their intake. Therefore, analytical strategies to simultaneously monitor the occurrence of these alkaloids should be developed to ensure food safety an comply with regulations. Accordingly, this work proposes an efficient multicomponent analytical strategy for the simultaneous extraction of these alkaloids from commercial bakery products. The analytical method was validated and applied to the analysis of 15 samples, revealing that 100% of them contained at least one of the target alkaloids, in some cases exceeding the maximum limits legislated. Moreover, in two samples the 3 different alkaloid families were detected. These results confirm the importance of simultaneously monitoring these alkaloids in food and highlight also considering some opium alkaloids in current legislation.

The Toxicity and Attenuation Methods of Toxic Chinese Materia Medica for its Reasonable Application: A Review.

Over a millennia, traditional Chinese medicine (TCM) has been used to treat various diseases in China. In recent years, more and more Chinese materia medica (CMM) have been studied in scientific research projects, applied in clinical practice, and their extracts have even appeared in some health products. However, the toxicity of some CMM is often overlooked, including hepatotoxicity, nephrotoxicity, neurotoxicity, cardiotoxicity, etc. In this review, the toxic components and their toxicological mechanisms of some toxic CMM were listed according to the chemical structure classification of toxic components. Afterwards, the traditional methods (processing and compatibility) and modern methods (structural modification, biotransformation, etc.) of attenuation of CMM were discussed. Since ancient times, it has been said that "fight fire with fire, fight poison with poison," and toxic CMM are of great significance in the treatment of difficult and severe diseases. The rational application of toxic CMM and their components in clinical practice was also exemplified in this review. While the pharmacological effects of TCMs have been emphasized, the scientific attenuation and rational application of toxic components should be concerned. We hope this review can provide a reference for future related research.

Screening of drugs and homeopathic products from Atropa belladonna seed extracts: Tropane alkaloids determination and untargeted analysis.

Homeopathic products are still a controversial issue in modern medicine, understood as complementary or alternative medicine (CAM). In this particular case, homeopathic products prepared from Atropa belladonna extracts may present specific problems due to the effects derived from its components. This article applies a simple, rapid, reliable method to the analysis of different homeopathic products obtained from Atropa belladonna; drugs containing high concentration of plant extracts; and Atropa belladonna seeds. The method was based on a simple solid-phase preconcentration method followed by ultra-high pressure liquid chromatography (UHPLC) coupled to high resolution mass spectrometry using Exactive-Orbitrap as an analyser. An in-house database was set and atropine and scopolamine were the compounds detected at highest concentrations in homeopathic products from Atropa belladonna extracts (4.57 and 2.56 µg/kg, respectively), in Belladonna ointment (4007 and 1139 µg/kg, respectively) and Belladonna seeds (338 and 32.1 mg/kg, respectively). Other tropane alkaloids such as tropine, apoatropine, aposcopolamine, tropinone, homatropine, and anisodamine were detected at lower concentrations (0.04-1.36 µg/kg). When untargeted analysis was performed, other tropane alkaloids were identified in the tested samples, such as ecgonine (0.003 µg/kg), benzoylecgonine (0.56 µg/kg), calystegines A (19.6 µg/kg), B (33.1 µg/kg), and C (1.01 µg/kg). Finally other compounds present in the homeopathic products, such as sugars (fructose, glucose, and lactose) or amino acids (valine, ornithine, leucine, and phenylalanine), were identified.

Interaction of competitive antagonists: the anti-curare action of hexamethonium and other antagonists at the skeletal neuromuscular junction.

1. In the rat isolated diaphragm preparation hexamethonium and other low potency competitive antagonists of acetylcholine (ACh), including gallamine and hyoscine butylbromide, reverse block by the potent antagonists tubocurarine, pancuronium and alcuronium. 2. In the presence of tubocurarine, hexamethonium increases the amplitude of the end-plate potential without increasing the quantal content. It enhances the response to ACh applied iontophoretically to the end-plate but does not enhance the response to ACh applied in the bath. 3. The anti-curare effect of hexamethonium is abolished in the diaphragm of the rat, guinea-pig and mouse by inhibitors of acetylcholinesterase. The effect is not observed in the indirectly stimulated toad sartorius muscle. 4. The effect is explained if tubocurarine does not dissociate appreciably in the time taken for ACh to achieve high occupancy of receptors, so that a fraction of receptors is completely excluded from occupation by ACh. Equilibration with hexamethonium reduces the fraction excluded by tubocurarine and the transmitter now competes with hexamethonium for more receptors and produces a larger response. 5. On the basis of this explanation the half-time for dissociation of tubocurarine must be about 1 millisecond. It follows that tubocurarine does not act competitively with ACh at synapses when transmitter action is sufficiently brief, and that its binding to the receptor is probably diffusion-limited.

Modification by hexamethonium of the muscarinic receptors blocking activity of pancuronium and homatropine in isolated tissues of the guinea-pig.

In the guinea-pig left atrium, hexamethonium (C6) (0.1-3 mM) caused a parallel rightward shift of concentration-response curves for the negative inotropic response to carbachol (CCh) and oxotremorine (Oxo), the dose ratios obtained with the latter agonist being significantly greater than those for CCh at all concentrations of C6 investigated. In the presence of C6, the muscarinic receptor blocking activity of homatropine (20 microM) or of pancuronium (0.3-2.7 microM) appears to be reduced but if the effect of hexamethonium on concentration-response curves to the agonists is taken into consideration, the dose ratios produced by the combination of C6 with either homatropine or pancuronium were essentially as predicted for the combination of 2 competitive antagonists. The difference in the affinity of pancuronium for cardiac muscarinic receptors and ileal muscarinic receptors was also reduced in the presence of hexamethonium (0.3 mM).

Failure of gallamine and pancuronium to inhibit selectively (-)-[3H]quinuclidinyl benzilate binding in guinea-pig atria.

Binding of (-)-[3H]quinuclidinyl benzilate (QNB) to muscarinic sites in guinea-pig atrial and ileal longitudinal muscle homogenates showed the presence of a single population of binding sites in atria (KD = 41 (32-53) (95% confidence limits) pM; Bmax = 0.225 +/- 0.02 pmol/mg protein (3)) and two binding sites in the ileum (KD = 20.9 (8.8-49) pM and 11.3 nM; Bmax = 0.436 +/- 0.09 and 11.85 +/- 2.63 pmol/mg protein (4), respectively). Atropine, gallamine, and pancuronium displaced (-)-[3H]QNB binding from the high affinity binding sites in the two tissues in a dose-dependent manner with -log Ki values of 8.6, 6.4, and 6.9, respectively, in atria and 8.7, 6.8, and 6.9, respectively, in ileal longitudinal muscle. The lack of selectivity of gallamine and pancuronium in binding experiments differed from results obtained in isolated tissue experiments where these antagonists showed a marked difference in their ability to antagonize cholinomimetics in the two tissues. In addition, the Ki values for gallamine and pancuronium in ileal homogenates were ca. 130- and 16-fold lower, respectively, than their KB values determined from isolated tissue experiments. Attempts to correlate data from binding experiments and isolated tissue experiments using combinations of antagonists led to variable results attributed to differences in the rates of dissociation of the antagonists from muscarinic receptors. It is concluded that the interaction of gallamine or pancuronium with agonists or antagonists at muscarinic receptors is not a simple bimolecular interaction.