The influence of caffeine on ethyl glucuronide levels in rat serum and in rat hair.

BACKGROUND: Ethanol and caffeine are the most widely used psychoactive substances in the world, with an observed steady increase in the combined consumption of alcohol and caffeine. Specific signs of ethanol-caffeine interactions have been reported both in humans and in animals. The metabolic effects of these interactions have not been fully elucidated. There are no published reports on the influence of caffeine on ethyl glucuronide (EtG) formation. EtG is a direct metabolite of ethanol and is very often used as a biomarker of alcohol consumption. Here, we investigated the influence of caffeine on the formation of EtG in rat plasma and EtG incorporation into the hair. METHODS: Studies were conducted on three male Wistar rat groups, each receiving either ethanol at 3g/kg/day, ethanol (at the same dose) with caffeine at 3mg/kg/day, or caffeine at 3mg/kg/day for four weeks. EtG and caffeine levels were evaluated in hair and in blood after the last administration. RESULTS: Blood EtG levels after the administration of ethanol together with caffeine were significantly higher than after the administration of ethanol alone. EtG levels in rat hair in the ethanol-and-caffeine group were also higher than in the ethanol-only group, but the difference was not statistically significant. CONCLUSION: This study shows the possible effect of ethanol and caffeine co-administration on EtG formation. Caffeine stimulates EtG synthesis resulting in increased blood and, possibly, hair levels of this metabolite. However, the role of these changes in estimating alcohol consumption requires further studies.

Difficulties in interpretation when assessing prolonged and subacute exposure to the toxic effects of chlorine.

The purpose of this study was a toxicological interpretation of exposure to chlorine with unusual course. Medical, clinical and court records, as well as reviews of the literature, served as the basis for this interpretation. The first case of poisoning concerns a 52-year-old man who for a short time (probably several hours), during the industrial cleaning of facilities with sodium hypochlorite, was exposed to chlorine in a presumed high concentration. The man was obese and suffered from hypertension and moderate atherosclerosis, and therefore could be more susceptible to the toxic effects of chlorine. After exposure no pulmonary edema or symptoms typical for acute respiratory distress syndrome were present. The second case concerns the chronic poisoning of a 56-year-old man who worked for eight years, 8 h a day, 5 days a week, in a room which was next to a chlorination room. In this chamber technical sodium hypochlorite was stored and dosed. In both cases, determining a cause and effect relationship between exposure to toxic and allergic agents in the form of active chlorine, and the onset of symptoms may be difficult. The findings described above in the first and second case are particularly important in cases of compensation claims and may have a completely different etiology than previously described in medical literature.

THE EFFECT OF METHANOL USED AS VEHICULUM ON SERUM PHENACETIN CONCENTRATION IN THE RAT.

The xenobiotic absorption process is dependent on many factors, related both to the substance and form of its administration. During administration of small amounts of drugs, the effect of vehiculum on drug fate in the body becomes also evident. The intensity of absorption depends on numerous factors not necessarily related to the substance and its formulation, and also on biotransformation and active transport processes. Additional problem is the fact that many medicines are lipophilic compounds and insoluble in the water (e.g. phenacetin). Methanol and its aqueous solutions facilitate administration to the experimental animals, in the dissolved form of a number of medicines practically insoluble in water. Taking into consideration that methanol is particularly for rats, of low toxicity, it is quite frequently applied as vehiculum. The aim of this study was to investigate the potential interactions that may occur during the use of methanol as vehiculum and compare changes when were used solution 1% of carboxymethylcellulose. The study was performed on male Wistar rats. The tests were performed using phenacetin, which is recognized as biomarker of CYP 2E 1 isoform activity. Phenacetin was given per os in a single dose of 100 mg/kg b. w. Various procedures of phenacetin administration were tested, including solubilization in methanol or suspension in 1% water solution of carboxymethylcellulose. The results of this study show that methanol influences the phenacetin bioavailability and kinetics. Comparing the administration of this drug in methanol solutions against 1% of carboxymethylcellulose, it is in the case of phenacetin triple increase in AUC0-4 h. The presence of methanol affects the shape of kinetic curves of phenacetin causing higher their course until 4 hours after administration.

[A rare case of infant poisoning due to accidental administration of 1,2,3-triketohydrinden hydrate (ninhydrin)]. / Rzadki przypadek zatrucia niemowlecia wskutek blednego podania wodzianu 1, 2, 3-trójketohydrindenu (ninhydryny).

The paper presents a case of medical malpractice during the test for phenylketonuria. The authors analyzed all documents collected in the course of the investigation of infant poisoning due to accidental administration of ninhydrin. The medical assessment was based on an extensive review of the case history, as well as on spectroscopy (FT-IR), chromatography and chemical analysis findings that allowed for confirming the presence of the toxic substance in the evidence material collected during the initial investigation. The obtained results confirmed the presence of ninhydrin in the tea cup and in the teaspoon, which were used to prepare the diagnostic medium. No ninhydrin was found in other investigated materials. The employment of routine research methods, including GC-MS, FT-IR and UV-VIS, allowed for detection and identification of the pure chemical form of ninhydrin, as well as its color complex with amino acids. The detailed case analysis, as well as the variability of extensive evidence material collected during the investigation allowed for determining the identity of persons responsible for accidental administration of the poisoning substance to the infant.

In vivo effect of 5- and 8-methoxypsoralens and cimetidine on R,S-warfarin metabolism in rat.

Several forms of cytochrome P-450 (CYP) metabolize R,S-warfarin in a regio- and enantioselective manner, therefore R,S-warfarin can be recognized as a metabolic probe for a number of CYP isoforms. We have applied a warfarin model in vivo in order to estimate the inhibitory properties of 5- and 8-methoxypsoralens on the activity of rat CYP isoforms. The area under the serum concentration versus time curve (AUC) values from time zero to 5 h for R- and S-warfarin and their metabolites were calculated. R,S-Warfarin kinetics measurements were made three times on each rat: a week before the 7-days inhibitor treatment, 3 h after the last dose of inhibitor and 3-7 days after the inhibitor was withdrawn. The inhibitory effect of cimetidine on CYP 2C11 and CYP 2C6 activities was confirmed in this approach and can be recognized as a positive control in validation of the in vivo experiment. Both 5- and 8-methoxypsoralen inhibited CYP 2C6 activity as the respective AUC for metabolite/warfarin enantiomer ratio decreased significantly. The activity of CYP 2C6 in 5- and 8-methoxypsoralen-treated rats increased over control values after the inhibitor was withdrawn. It was also observed that cimetidine additionally inhibits the absorption of R,S-warfarin and a decrease in the sum of AUC for R- and S-enantiomers became evident in spite of inhibition of the activity of both CYPs. 5-Methoxypsoralen modified the serum R-warfarin/S-warfarin ratio and a selective increase in AUC(S-warfarin) was observed, the most pronounced being after the inhibitor was withdrawn. This effect is not likely to be mediated by P-glycoprotein (P-gp) because quinidine--, a P-gp inhibitor at a dose of 15 mg kg(-1) body wt.--did not influence the AUC for either enantiomer.