Isidora Samojlik

Antioxidant and hepatoprotective potential of essential oils of coriander (Coriandrum sativum L.) and caraway (Carum carvi L.) (Apiaceae).

Essential oils of Coriandrum sativum L. and Carum carvi L. fruits were analyzed by gas chromatography-mass spectrometry and assayed for their in vitro and in vivo antioxidant activity and hepatoprotective effect against carbon tetrachloride (CCl(4)) damage. The in vitro antioxidant activity was evaluated as a free radical scavenging capacity (RSC), measured as scavenging activity of the essential oils on 2,2-diphenyl-1-picrylhydrazyl (DPPH(*)) and OH radicals and effects on lipid peroxidation (LP) in two systems of induction. Some liver biochemical parameters were determined in animals pretreated with essential oils and later intoxicated with CCl(4) to assess in vivo hepatoprotective effect. Tested essential oils were able to reduce the stable DPPH(*) in a dose-dependent manner and to neutralize H(2)O(2), reaching 50% neutralization with IC(50) values of <2.5 microL/mL for Carvi aetheroleum and 4.05 microL/mL for Coriandri aetheroleum . Caraway essential oil strongly inhibited LP in both systems of induction, whereas coriander essential oil exhibited prooxidant activity. In vivo investigation conferred leak of antioxidative capacity of coriander essential oil, whereas the essential oil of caraway appeared promising for safe use in folk medicine and the pharmaceutical and food industries.

Chemical Composition, Antioxidant and Antibacterial Properties of Achillea collina Becker ex Heimerl s.l. and A. pannonica Scheele Essential oils

The in vitro antioxidant and antimicrobial activities of two Achillea millefolium (Adanson) Koch s.l species essential oils (A. collina Becker ex Heimerl s.l. and A. pannonica Scheele, Asteraceae) originating from the Golija and Radan mountains (Serbia) were investigated. The chemical profiles of the essential oils were evaluated by GC-MS. Antioxidant activity was assessed as free radical scavenging capacity (RSC) towards 2,2-diphenyl-1-picrylhydrazil (DPPH) radicals, together with effects on lipid peroxidation (LP). Antibacterial activity was examined on 21 bacterial strains. Based on the chemical composition of the essential oil, A. collina s.l. from Mount Golija was classified as a chamazulene chemotype (tetraploid). The high percentage of oxygenated monoterpenes and absence of azulene in the essential oil obtained from A. pannonica from Radan pointing that this population is octaploid. Essential oil of A. pannonica expressed stronger antimicrobial activity on almost all tested bacteria. Furthermore, this essential oil expressed higher scavenging effects on DPPH radical (IC50 = 0.52 comparing to 0.62 μg/mL). Only in the LP evaluation, essential oil of A. collina s.l. from Golija exhibited stronger antioxidant activity (IC50 = 0.75 comparing to 2.12 μg/mL).

Impact of origin and biological source on chemical composition, anticholinesterase and antioxidant properties of some St. John's wort species (Hypericum spp., Hypericaceae) from the Central Balkans.

The study shows the influence of the origin of plant material and biological source on the in vitro antioxidant (neutralization of DPPH and OH radical, nitric oxide, and inhibition of lipid peroxidation) and anticholinesterase activity of chemically characterized and quantified ethanol extracts of ten St. John’s wort samples. The investigated samples were: five Hypericum perforatum species representatives collected at different localities, one commercial sample of Hyperici herba purchased at a local market and four Hypericum species autochtonous to the Balkan Peninsula (H. maculatum subsp. immaculatum, H. olympicum, H. richeri subsp. grisebachii and H. barbatum). All the examined extracts exhibited notable antioxidant potential, but in most of the cases indigenous Hypericum species expressed stronger effects compared to the original source of the drug, H. perforatum. The changes in the content of phenolic compounds, especially flavonoids, hyperforin and hypericin, related to the source of the drug affected the investigated activities. Since all of the investigated species have shown prominent inhibition of acetylcholinesterase in vitro activity, they could be further investigated as potential substances in preventing of Alzheimer’s disease.

The influence of essential oil of aniseed (Pimpinella anisum, L.) on drug effects on the central nervous system

Anise (Pimpinella anisum L.; Apiaceae) and its essential oil have been widely used in folk medicine, pharmacy and food industry. Since there are some data about the impact of anise on functions of central nervous system (CNS), the issue of possible interactions with drugs acting in CNS should be considered. This survey aimed to examine the influence of aniseed essential oil (EO) intake on the effects of drugs that act in CNS. The chemical profile of essential oil determined by GC-MS revealed as the main components: trans-anethole (88.49%), γ-himachalene (3.13%), cis-isoeugenol (1.99%), and linalool (1.79%). The effects of codeine, diazepam, midazolam, pentobarbital, imipramine and fluoxetine were tested in mice after 5days of peroral pretreatment with human equivalent dose of aniseed EO (0.3mg/kg). The intake of EO led to significant increase of analgesic effect of codeine. The motor impairment caused by midazolam was enhanced in the group treated by EO. The application of diazepam decreased the number and percentage of entries in open arm in elevated maze plus test in the group pretreated with EO indicating augmented effect of drug on motor activity. EO pretreatment caused significant shortage of pentobarbital induced sleeping time when compared to control. The decrease in antidepressant effect of imipramine and fluoxetine was diminished by the pretreatment with aniseed EO. Based on the results of this study we conclude that concomitant intake of aniseed EO preparations and drugs that act on CNS should be avoided due to potential herb-drug interactions, which also need further clinical confirmation.

Acute and Chronic Pretreatment with Essential Oil of Peppermint (Mentha × piperita L., Lamiaceae) Influences Drug Effects

The appearance of common and self‐initiative usage of various herbal preparations in everyday practice and life imposes the question of possible interactions with drugs. This survey examined the influence of acute and chronic peppermint oil (PO – Mentha × piperita L., Lamiaceae; prepared as emulsion for oral use) on pentobarbitone‐induced sleeping time, analgesic effect of codeine and impairment of motor coordination caused by midazolam in mice. The chemical profile of essential oil was determined by GC‐MS. Applied doses of PO were 0.1 and 0.2 mL/kg. Chronic PO intake (in both doses) led to significant decrease of analgesic effect of codeine, while acute intake of PO did not change this effect. Acute PO pretreatment in higher dose caused significant prolongation of pentobarbitone‐induced sleeping time, while it was significantly shortened by chronic PO pretreatment at the same dose. Midazolam effect was enhanced and prolonged significantly by chronic PO intake at higher dose, while acute intake of PO did not change this effect. Gut motility was increased only by acute intake of higher PO dose. Regarding the fact that PO produces changes in tested drug effects, the interaction between drugs and phytopreparations containing PO should be additionally followed/confirmed in humans. Copyright

Ethanol Concentrations in Antemortem Blood Samples Under Controlled Conditions

AIM The change of antemortem blood alcohol concentration (BAC) in inadequately processed samples was examined. METHODS The study was performed on nine healthy, sober volunteers after overnight fasting. Blood samples were divided into groups and stored, with or without NaF, for varying time periods (12, 24 and 48 h) and at different temperatures (4 degrees C and 20 degrees C). BAC analysis was performed by the gas-chromatography method. RESULT All groups showed very low values of BAC. CONCLUSION Surprisingly, this study showed no ethanol production in improperly processed antemortem blood samples in healthy and sober individuals who were subjected to overnight fasting.

The activity of liver oxidative enzymes after single and multiple grapefruit juice ingestion

In the recent time, several in vitro and in vivo studies have shown the inhibitory effect of grapefruit juice on metabolism of xenobiotics catalyzed by liver oxidative enzymes including cytochrome P450 izoenzymes. However, all these experiments were done with a single dose of grapefruit juice. The primary aim of this study was to evaluate if the chronical ingestion of grapefruit juice can cause enzyme activity alteration as well as a single dose. Three groups of male mice were used: the control group, the group which was administered 0.2 mL of grapefruit juice per os 10 days and the group which was administered single dose of 0.5 mL grapefruit juice per os 90 min. before the sacrificing. After the sacrificing of animals, liver was homogenized with appropriate buffer, and the activity of oxidative liver enzymes: xanthine oxidase (XOD), peroxidase (Px), catalase (CAT), lipid peroxidase (LPx), glutathion peroxidase (GSH-Px) and liver glutathion contents (GSH) were detected by standard methods. The results show that the enzyme activity of liver MFO was changed according to a single or multiple grapefruit juice ingestion. The grapefruit juice in a single oral dose significantly decreases the activity of xanthine oxidase, glutathion peroxidase, lipid peroxidase and liver glutathion contents, and has no effect on activity of catalase and peroxidase. The multiple grapefruit ingestion increases the activity of XOD, GSH-Px, LPx, Px and GSH, while the activity of CAT enzyme is unchanged. The chronical and single grapefruit ingestion has no effect on relative liver weight, but the liver protein content is significantly decreased after the multiple oral grapefruit juice ingestion.

Methadone-Related Deaths – Epidemiological, Pathohistological, and Toxicological Traits in 10-year Retrospective Study in Vojvodina, Serbia†

The number of methadone‐related deaths (MRDs) during a 10‐year period (2002–2011) in the region of Vojvodina, Serbia, was increased. The cases were evaluated according to epidemiological parameters, pathohistological findings, and toxicological screening. The majority of victims were men, aged from 20 to 38. Pathohistologically, the signs of acute focal myocardial damage were present in the heart of victims with drug abuse history shorter than 2 years, while both signs of recent and chronic focal myocardial damage were developed among victims with longer drug abuse history (2–5 years). In postmortem blood samples of 54.84% of victims, methadone was detected in combination with diazepam, both in therapeutic range. Alcohol was absent in most cases. Other detected drugs were antipsychotics and antidepressants in therapeutic concentrations. These findings raise the attention to the concomitant use of methadone and benzodiazepines with the need for further studies to clarify the mechanism of death in such cases.

Fatal Intoxication Because of Trihexyphenidyl

Abstract:  Trihexyphenidyl (THP) is an anticholinergic agent with forensic toxicological interest. We present a case of a 59‐year‐old woman with a history of paranoid disorder, who was found dead in the house where she lived alone. The autopsy findings revealed no marked pathological changes. Toxicological analysis based on gas chromatography–mass spectrometry (GC–MS) analysis revealed THP and its major metabolite (hydroxy—THP) in blood and urine, with THP concentrations of 0.053 and 0.560 mg/L, respectively. The blood and urine ethanol concentrations were low 0.096 and 0.100 g/L, respectively. Based on these results, we determined the cause of death to be THP poisoning. It is suggested that rare case of death associated with THP overdosage should be taken in conjunction with central nervous system depressants (benzodiazepines, ethanol) and/or with other pathological disorders. Thus, our case could not be supportive for this allegation.

Herb-drug interactions: the influence of essential oil of caraway (Carum carvi L.) on the pharmacokinetics of paracetamol

Methods The essential oil (EO) of caraway, prepared as emulsion for peroral use, was applied to male mice during 5 consecutive days. Paracetamol, in the dose of 200 mg/kg, was applied p.o. or i.p. 2 hours after the last EO dose. Blood samples for pharmacokinetic assay were collected from the tail vein before paracetamol intake and 10, 30, 60, 90 and 120 min thereafter. Blood concentrations of paracetamol were determined by HPLC and the pharmacokinetic parameters were calculated using the WinNonlin software.