Vasorelaxant effects and mechanisms of action of Heracleum sphondylium L. (Apiaceae) in rat thoracic aorta.

ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Heracleum sphondylium L. (HS) are used in traditional medicine to treat hypertension. To provide pharmacological basis for this use, we investigated the vasorelaxant effects of a dichloromethane extract of HS (HSDE) and the mechanisms involved. MATERIALS AND METHODS: Activity of HSDE was evaluated on rat isolated thoracic aortic rings. RESULTS: HSDE induced vasorelaxation in phenylephrine (PE, 10(-6)mol/L) and high KCl-(6×10(-2)mol/L) pre-contracted aortic rings that was independent on the presence of endothelium. HSDE markedly decreased extracellular Ca(2+)-induced contraction in high-KCl and PE pre-challenged rings. It also inhibited the intracellular Ca(2+) release sensitive to PE (10(-6)M). The relaxant effect of HSDE were blunted by 4-amino-pyridine (4-AP, 10(-3)mol/L), an inhibitor of voltage-dependent K(+) channels. CONCLUSION: Our results provide the first evidence that a dichloromethane extract of Heracleum sphondylium L. exhibits vasorelaxant properties through endothelium-independent mechanisms involving the inhibition of Ca(2+) mobilization and changes in Kv channel conductances. These data argue for its use as antihypertensive therapy in traditional medicine.

Estimation of ochratoxin A in the human blood of Romanian population.

UNLABELLED: Ochratoxin A (OTA) is a toxic secondary metabolite of fungi belonging to the Aspergillus and Penicillium genera, its presence in human blood being the primary indicator of exposure. AIM: In the present study we determined OTA in 38 blood samples collected from healthy Romanian subjects of both genders. MATERIAL AND METHODS: The OTA was determined through the direct, competitive, solid-phase immunoenzymatic method; the minimum quantification limit for determining OTA in serum samples was 0.0289 ng/mL. RESULTS: The positive sample percentage was 100%. OTA concentrations varied between < 0.04 ng/mL and 1 ng/mL. There were no significant differences between OTA concentrations in men versus women (0.24 +/- 0.20 ng/mL versus 0.17 +/- 0.15 ng/mL, p = 0.3527). CONCLUSIONS: The analyzed blood samples exhibit a very high degree of exposure to OTA, but in only approximately 10% of the subjects exceeded 0.5 ng/mL, considered the threshold for OTA-induced renal pathology.

Multi-analytic detection of antibiotic residues in honey using a multiplexing biochip assay.

UNLABELLED: Contamination of honey may occur through the common use of antibiotics and chemotherapeutics by certain beekeepers to cure or to prevent bacterial or other bee diseases. In order to protect human health the use of antimicrobials in apiculture is usually strictly regulated or banned. LC/MS/MS is currently regarded the tool of choice for analysis of drug residues in animal-derived food. Screening methods (immunoassays and biosensors) are also required and are being developed. AIM: The present paper reviews one of the most recent methods for analysis of drug residues in honey and also the abridged method validation according to the criteria set by Commission Decision 2002/657/EC for simultaneous determination of drug residues in honey samples using a test panel which screens for quinolones (QNL), ceftiofur (CEFT), thiamphenicol (TAF), streptomycin (STR), tylosin (TYL) and tetracyclines (TCN). MATERIAL AND METHODS: A chemiluminescence--based biochip array sensing technique has been applied. Using a multiplex approach, metabolites of CEFT, TAF, QNL, STR, TCN and TYL were simultaneously detected in honey samples. RESULTS AND DISCUSSION: The simultaneous immunoassays showed specificity for the target analytes. The limits of detection were between 1 microg/kg for TAF and 9 microg/kg for TCN. Good linearity was obtained, with determination coefficients higher than 0.980. The decision limit (CCalpha) and the capability of detection (CCbeta) were well below established Reference Point for Action (RPA). Method applicability was demonstrated through application to various kinds of honey. CONCLUSIONS: Biochip array technology allows simultaneous and selective multi-analytic measurement of antimicrobials in honey at levels well below established Reference Point for Action (RPA). The performance of biochip screening method was comparable to that achieved for the confirmatory LC/MS/MS method.

Estimation of dietary intake of cadmium and lead through food consumption.

Cadmium and lead are toxic metals occurring in the environment naturally and from anthropogenic activities and can lead to chemical contamination of products entering in the human food chain. The consumption of polluted food is the main source of lead and cadmium intake in the non-smoking population. Lead is a heavy metal that can affect different organs and systems in humans including the peripheral and central nervous system, the gastrointestinal tract, muscles, kidneys, and the hemopoetic system. Neurological symptoms can range from fatigue, headache, and lethargy to peripheral neuropathy, severe convulsions, encephalopathy, and even coma. The direct neurotoxic actions of lead include apoptosis, excitotoxicity. Lead has been associated with impaired neurobehavioral functioning in children, decrements in intelligence quotient (IQ) while the critical effect of long-term exposure to cadmium is renal tubular dysfunction, which is irreversible; chronic renal failure is the final and severe endpoint. Cadmium is able to induce bone damage (Itai-ltai). The body burden of cadmium and lead depends mostly on the dietary intake of these elements. This paper aims to present a brief overview of cadmium and lead contents present in foodstuffs from different countries and the estimated dietary intake of cadmium and lead through food consumption. It has been shown that in some countries the concentrations of cadmium and lead contained in foodstuffs are higher than normal therefore the health of the people consuming them is in danger.

[Nitrates and nitrites in meat products--nitrosamines precursors]. / Nitratii si nitritii din preparatele din carne-precursori ai nitrozaminelor.

AIM: To determine the content in nitrates and nitrites and the formation of two nitrosamines (N-nitrosodimethylamine--NDMA, and N-nitrosodiethylaamine--NDEA) in samples of chicken ham, dry Banat salami, dry French salami, traditional Romania sausages, and pork pastrami. MATERIAL AND METHODS: Nitrites were determined by spectrophotometry with Peter-Griess reagent, and nitrates by the same method after reduction to nitrites with cadmium powder. High performance liquid chromatography with UV detection was used to determine nitrosamines. RESULTS: The initial concentration of nitrates, nitrites, NDMA and NDEA in the samples ranged as follows: 14.10-60.40 mg NO3/kg, 2.70-26.70 mg NO2/kg, from non-detectable to 0.90 microg NDMA/kg, and from non-detectable to 0.27 microg NDEA/kg, respectively. After 28 days the concentrations were: 3.24-17.1 mg NO3/kg, 0.04 -1.87 mg NO2/kg, 0.8-29 microg NDMA/kg, and 11.6-61.9 microg NDEA/kg, respectively. CONCLUSIONS: The decreased nitrate and nitrite and increased NDMA and NDEA concentrations prove that in food products nitrosamines are formed due to residual nitrite during their preservation. The determination of nitrasamines revealed levels much above the admitted maximal concentration for these food products.

Protective effects of selenium on acrylamide toxicity in the liver of the rat. Effects on the oxidative stress.

UNLABELLED: Acrylamide (AA), obtained for the first time by Moureu in Germany in 1893, is presently used as polyacrylamide in water treatment and wastewater treatment, paper and pulp processing, mineral processing, crude-oil production processes. Acrylamide is a chemical product formed when frying, roasting, grilling or baking carbohydrate-rich foods at temperatures above 120 degrees C. Acrylamide is thus found in a number of foods, such as bread, crisps, French fries and coffee. Tobacco smoking also generates substantial amounts of acrylamide. Acrylamide administration is associated with significant increase of oxidative stress parameters; acrylamide caused disturbances in the oxidative status and enzyme activities and the effect was pronounced with the high doses. MATERIAL AND METHODS: This study investigates the effect of selenium (as sodium selenite and as a selenium dietary supplements--Celnium) on the oxidative stress in Wistar rats which received high doses of acrylamide. RESULTS: The administration of sodium selenite and selenium dietary supplements (Celnium) significantly increased GSH and GPx levels and decreased MDA compared to group which received only acrylamide. CONCLUSIONS: Our results show that sodium selenite and selenium dietary supplements (Celnium) can partially prevent the biochemical changes in the liver of the rats which received high doses of acrylamide.

Food-drug interactions: grapefruit juice.

Food-drug interactions are increasingly recognized as important clinical events which may change significantly the bioavailability of oral administrated drugs. Grapefruit juice (GFJ) demonstrated multiple interactions with drugs leading to loss of the therapeutic effects or increased side-effects. GFJ decreases pre-systemic metabolism through a) competitive or mechanism-based inhibition of gut wall CYP3A4 isoenzymes and b) P-glycoprotein (P-gp), c) multidrug resistance protein-2 (MRP2) or d) organic anion-transporting polypeptide (OATP) inhibition. Although, GFJ presents high amounts of flavonoids (e.g. naringin, naringenin), furanocoumarins (e.g. 6',7'-dihydroxybergamottin, bergamottin) are the main chemicals involved in the pharmacokinetic interactions. As compounds of GFJ show additive or synergistic effects, all the major furanocoumarins are necessary for the maximal inhibitory effect. Also, related citrus fruits (sweeties, pummelo and sour orange) or various plants containing furanocoumarins may present pharmacological interactions, yet to be discovered.

Grapefruit juice--drug interactions: importance for pharmacotherapy.

In spite of known health benefits of grapefruit juice, its consumption in combination with drugs requires caution. The drugs most susceptible to pharmacokinetic interactions with clinical significance are those with narrow therapeutic index and low bioavailability due to important first-pass metabolism. Most vulnerable populations are elderly, cirrhotics, subjects with genetic polymorphisms and individuals taking other CYP3A4 inhibitors. The major drug classes that have been reported to present interactions with grapefruit juice are antiallergics, antibiotics, antimalaria drugs, anxiolytics, calcium channel blockers, HIV protease inhibitors, HMG-CoA reductase inhibitors; the degree of pharmacokinetic interaction varies among the compounds of the same class.

[Flavonoids--bioactive compounds in fruits juice]. / Flavonoidele--componente bioactive din sucuri de fructe.

UNLABELLED: Since 1989, grapefruit juice is reported to modify, with clinical implications, the pharmacokinetic of a series of drugs such as calcium channel blockers that are dihydropyridine derivates and/or some HMGCoA reductase inhibitors. All these drugs are metabolized to a large extent by the most abundant human isoform of cytochrome P450, CYP3A4. Grapefruit inhibits the cytochrome P450 3A4 enzyme system responsible for the oxidative metabolism of many orally administered drugs. The most important compounds of GFJ considered to be involved in the pharmacokinetic interaction are flavonoids (naringin, naringenin, narirutin, quercetin, kaempferol, hesperidin, neohesperidin, didymin, and poncirin), furanocoumarins (6',7'-dihydroxy-bergamottin, bergamottin, bergamottin-6',7'-epoxide, bergapten, epoxy-bergamottin) and sesquiterpens (noot-katone). MATERIAL AND METHOD: The experimental researches had as object the comparative study of total content of flavonoidic compounds, like naringin in different fruit juices: citric fruit (white, pink and red grapefruit), apples, pears--industrial or laboratory prepared juices (by squeezing). They praised a different content in flavonoidic compounds for citric and for the rest of analyzed fruits. RESULTS: For grapefruit juices the concentrations in flavonoidic compounds are higher in total fruit juice: 143.86 mg/100 mL in red, 131.47 mg/100 mL in pink and 84.21 mg/100 mL in white grapefruit juice. In juice prepared from fruit pulp, the concentrations were 81.92 mg/100 mL, 108.23 mg/100 mL and 65.76 mg/100 mL, respectively. The content in naringin, the most important flavanone in citrus fruit, varied between 1.98 and 51.2 mg/100 mL juice.

Biogenic amines determination in some Romanian meat products.

AIM: Biogenic amines are compounds synthesized in human body which in high concentration become toxic and lead to a wide range of symptoms as palpitations, nausea and headache. Meat products can contain high levels of biogenic amines. Ingestion of such product can cause severe illness. For these reason it becomes necessary to determine the biogenic amines levels in meat products. In our work we have determined the amount of some biogenic amines and the ration in which they are present in different type of fresh and processed meat products made by several producers. MATERIAL AND METHOD: Meat sample was homogenized with TCA 5%, than centrifuged at 4000 rpm and supernatant collected was eluted on a solid cartridge extraction. The extracted liquid was than analyzed on high performance liquid chromatography (HPLC) system in order to determine histamine, tyramine, cadaverine and putrescine. RESULTS: Concentration of biogenic amines such as histamine, tyramine, cadaverine and putrescine, find in the foodstuffs we have analyzed, showed significant differences. CONCLUSIONS: Our study indicates the presence of biogenic amines in Romanian meat products and signals to the risk of food consumption, for persons which are allergic or for those under classical monoamine-oxidase inhibitor drug therapy.

Total antioxidant status in the blood serum of rats after biogenic amines administration.

UNLABELLED: The aim of our study was to investigate the influence of biogenic amines on rat blood levels of total antioxidant status (TAS). Total antioxidant species refers to all circulating species in plasma including vitamin E, vitamin C, beta-carotene, uric acid, bilirubin, albumin as well as metal-binding proteins (e.g. ferritin or ceruloplasmin). MATERIAL AND METHOD: We worked on three series of Wistar male rats. Series I received histamine (10 mg/kg body) intra peritoneal (i.p.) single dose, Series II received tyramine (10 mg/kg body) intra peritoneal (i.p.) single dose and Series III received biogenic amines mixture (histamine, tyramine and cadaverine 5 mg/kg body) intra peritoneal (i.p.) single dose. At 72 hours after biogenic amines administration blood samples were collected and total antioxidant status was determined using a RANDOX kit for manual use. RESULTS: Our data shows that total antioxidant status present a significant decrease after 72 hours after amines administration as compared with initial moment, before administration. CONCLUSIONS: The biogenic amines decrease the level of the total oxidant status in rat blood serum and reduce the capacity of the antioxidant defense system. The amines administration as a mixture seems to have no cumulative effect on individual amine toxicity.