Ml Of Grapefruit Juice Research Articles

Co3O4 nanoparticles synthesized with rotten-grape extract for use in supercapacitors and oxygen evolution devices

Phytochemicals in grape fruit juice have never been considered as potential sources of surface modification, shape modification, and energy storage. In our study, we demonstrate the hydrothermal synthesis of Co3O4 nanostructures from grape fruit extracts. X-ray diffraction analysis revealed that Co3O4 nanostructures exhibit a cubic phase, while Fourier transform infrared spectroscopy identified several functional groups. An analysis of Co3O4 nanostructures using a scanning electron microscope revealed that uniformly distributed nanoparticles of Co3O4 were trapped in the carbon content of the spices during calcination. UV–visible spectrometer analysis of Co3O4 nanostructures reveals a wide range of optical bands. It was found that one mL of grape fruit juice provided the lowest optical band gap of 2.51 eV for Co3O4 nanostructures. Nanostructures of Co3O4 were studied under alkaline conditions for use in supercapacitors and oxygen evolution reactions. An aqueous solution containing 1 mL of assisted Co3O4 nanostructures exhibited an overpotential of 290 mV at a current density of 10 mA cm−2 in 1 M KOH. In addition, they showed a Tafel slope of 80 mV dec−1. When dissolved in 3 M KOH electrolyte, grape fruit juice assisted Co3O4 nanostructures showed a specific capacitance of 867 F/g at 1.5 A/g in 3 M KOH aqueous solution. A specific capacitance retention percentage of about 101.1 % was achieved after 40000 galvanic charge-discharge cycles. It has been shown that the total photochemistry of biomass waste can be tuned and enhanced to enhance the functional properties of nanostructures derived from rotten grape fruit extract in order to develop functional materials with high performance for a wide range of applications.

Pharmacokinetic and Pharmacodynamic Interactions between Food or Herbal Products and Oral Anticoagulants: Evidence Review, Practical Recommendations, and Knowledge Gaps.

Interactions between food and oral anticoagulants (OACs), particularly vitamin K antagonists such as warfarin, are widely recognized and may also be clinically relevant for direct OACs. Pharmacokinetic and pharmacodynamic interactions with food or herbs can lead to anticoagulation potentiation, increased risk of bleeding, or reduced drug efficacy, all compromising patient safety. We conducted a systematic search for randomized controlled trials (RCTs) on PubMed for assessments of interactions between OACs and various ingestants. Since the RCT evidence was slim, we also reviewed prospective longitudinal studies, case series, and case reports to identify possible associations between foods and anticoagulation therapy. We referred to basic or translational studies that shared putative explanations for such interactions, but we failed to identify high-quality evidence in most cases. The limited evidence, small sample size of the studies, conflicting results, and possible heterogeneity in the contents of herbal products prevent a conclusive assessment of these interactions. Existing evidence suggests that (1) cranberry juice consumption (up to 240 mL/d and probably even more) with warfarin is safe; (2) use of green leafy vegetables with a high daily content (more than 250 µg) of vitamin K should be cautioned for patients receiving warfarin, because it may decrease warfarin efficacy. It is also advisable for patients to maintain highly constant intake of green leafy vegetables to ensure stable warfarin effectiveness; (3) ginger, even in small quantities (excluding commercial ginger-flavored beverages, which contain only negligible amounts of ginger), and mango (more than one fruit) can both potentiate warfarin effects; (4) patients taking OACs should avoid St. John's wort due to diminished anticoagulant effect; and (5) consumption of less than 240 mL of grapefruit juice daily is unlikely to interact with OACs. Future longitudinal observational cohort studies and RCTs with larger sample sizes are needed to study specific interactions between food or herbal products and OACs.

Grapefruit juice containing rich hydroxyl and oxygenated groups capable of transforming 1D structure of NiCo2O4 into 0D with excessive surface vacancies for promising energy conversion and storage applications

Fabrication of an efficient electrode material is highly demanded for obtaining high energy conversion electrochemical system. In this study, we describe a green and innovative approach of using grape fruit juice as a high carrier of reducing and surface modifying agents for manipulating the surface properties of nickel‑cobalt bimetallic oxide NiCo2O4 nanostructures. Different amounts of grape fruit juice were used to discern its role on the morphological and surface vacancies of NiCo2O4 nanostructures during oxygen evolution reaction (OER). Importantly, the physical characterization revealed the morphological transformation of NiCo2O4 nanostructures from 1D nanorods to short range 0D nanoparticles. Furthermore, the surface studies have shown that NiCo2O4 nanostructures prepared with grapefruit juice have high density of surface vacancies and higher amount of Ni2+ and a Co2+ metallic ions on the surface of NiCo2O4 compare to pure NiCo2O4 nanostructures. The OER of electrodes modified with NiCo2O4 nanostructures, particularly (sample-2, 2 mL of grape fruit juice) gave rise to an overpotential value of 260 mV at 10 mAcm−2 in 1.0 M KOH aqueous solution along with high durability/stability for 40 h. Additionally, the obtained electrochemical impedance spectroscopy value of 80 Ω and active surface area of 18.1 μFcm−2 attested for the excellent OER performance of NiCo2O4 nanostructures (sample-2). Eventually, the proven enhancement in surface vacancies, alternation in the mixed oxidation states of both Ni and Co together with the morphological transformation that have been accomplished via the green, simple, and low-cost strategy of using grape juice make it a suitable option for large scale production of wide range of multifunctional metal oxides and related nanostructured materials for plethora of energy conversion and storage applications.

Urinary metabolic markers reflect on hepatic, not intestinal, CYP3A activity in healthy subjects

Intestinal cytochrome P450 3A (CYP3A) plays an important role in oral drug metabolism, but only endogenous metabolic markers for measuring hepatic CYP3A activity were identified. Our study evaluated whether hepatic CYP3A markers reflected intestinal CYP3A activity. An open-label, three-period, six-treatment, one-sequence clinical trial was performed in 16 healthy Korean males. In the control phase, all subjects received a single dose of intravenous (IV) and oral midazolam (1 mg and 5 mg, respectively). Clarithromycin (500 mg) was administered twice daily for 4 days to inhibit hepatic and intestinal CYP3A, and 500 mL of grapefruit juice was given to inhibit intestinal CYP3A. Clarithromycin significantly inhibited total CYP3A activity, and the clearance of IV and apparent clearance of oral midazolam decreased by 0.15- and 0.32-fold, respectively. Grapefruit juice only reduced the apparent clearance of oral midazolam by 0.84-fold, which indicates a slight inhibition of intestinal CYP3A activity. Urinary markers, including 6β–OH–cortisol/cortisol and 6β–OH–cortisone/cortisone, were significantly decreased 0.5-fold after clarithromycin administration but not after grapefruit juice. The fold changes in 6β–OH–cortisol/cortisol and 6β–OH–cortisone/cortisone did not correlate to changes in intestinal availability but did correlate to hepatic availability. In conclusion, endogenous metabolic markers are only useful to measure hepatic, but not intestinal, CYP3A activity.

Grapefruit juice nutritional profile

Based on the published data on the content of nutritive (NS) and biologically active substances (BAS) and the results of studies of various samples of domestic industrial grapefruit juice, the article presents the nutrient profile of grapefruit juice containing data about more than 30 NS and BAS. Grapefruit juice is one of the relatively low-calorie fruit juices - 100 ml of grapefruit juice contains an average of 39 kcal. Like other citrus juices, it is rich in organic acids, the main of which is citric acid (0.8-2 g/100 ml). Potassium, magnesium, vitamin C, as well as flavonoids (mostly narigin) are the most significant for the estimation of nutritional and biological value of grapefruit juice of industrial production. A glass of grapefruit juice contains, on average, about 10% of the daily requirement in potassium, 6% - in magnesium and about 100% - in vitamin C. The amount of flavonoids in a glass of grapefruit juice provides up to 60% of the adequate daily intake. Conducted studies of fresh grapefruits purchased in the trade network show that the content of potassium, magnesium and vitamin C in grapefruit juice of industrial production is comparable to the content of these micronutrients in fresh fruits.

Does consumption of red grapefruit juice alter naringenin concentrations in milk produced by breastfeeding mothers?

The content of certain ingredients of human milk, such as flavonoids, depend on the types and amounts of plant products consumed and may vary from woman to woman. The aim of the study was to determine to what extent consumption of an average amount of grapefruit juice (250 ml) affected naringenin content in human milk. A total of 14 breastfeeding mothers were included in the study. The subjects remained on a diet with restricted intake of naringenin for a total of five days except on the third day, when they drank a single serving of 250 ml of grapefruit juice. A considerable subject-to-subject variability in naringenin content was observed in both initial and subsequent determinations. Baseline concentration values, which may reflect naringenin content in the milk produced by the breastfeeding mother who eat an everyday (unmodified) diet, ranged from 420.86 nmol/l to 1568.89 nmol/l, with a mean of 823.24 nmol/l. Switching to the modified diet resulted in a decrease in naringenin concentrations to the mean value of 673.89 nmol/l measured 48 hours after the switch. The highest mean values were observed four and 12 hours after consumption of the juice, equalling 908.25 nmol/l (SD ± 676.84 nmol/l) and 868.96 nmol/l (SD ± 665.54 nmol/l), respectively. Naringenin is commonly found in human milk in quantities expressed in nmol/l, and its concentrations vary from woman to woman. Consumption of 250 ml of red grapefruit juice by breastfeeding mothers does not significantly alter naringenin concentrations in their milk.

Effect of grapefruit juice on the bioactivation of prasugrel.

The P2Y12 inhibitor prasugrel is a prodrug, which is activated after its initial hydrolysis partly by cytochrome P450 (CYP) 3A4. Grapefruit juice, a strong inactivator of intestinal CYP3A4, greatly reduces the activation and antiplatelet effects of clopidogrel. The aim of this study was to investigate the effects of grapefruit juice on prasugrel. In a randomized crossover study, seven healthy volunteers ingested 200 ml of grapefruit juice or water three times daily for 4 days. On day 3, they ingested a single 10 mg dose of prasugrel with an additional 200 ml of grapefruit juice or water. Plasma concentrations of prasugrel metabolites and the antiplatelet effect were measured. Grapefruit juice increased the geometric mean area under the plasma concentration-time curve (AUC(0-∞)) of the primary, inactive metabolite of prasugrel to 164% of the control value (95% confidence interval 122-220%, P = 0.008), without a significant effect on its peak plasma concentration (C(max)). The C(max) and AUC(0-∞) of the secondary, active metabolite were decreased to 51% (95% confidence interval 32-84%, P = 0.017) and 74% of the control value (95% confidence interval 60-91%, P = 0.014) by grapefruit juice (P < 0.05). The average platelet inhibition, assessed with the VerifyNow® method at 0-24 h after prasugrel intake, was 5 percentage points (95% confidence interval 1-10 percentage points) lower in the grapefruit juice phase than in the water phase (P = 0.034). Grapefruit juice reduces the bioactivation of prasugrel, but this has only a limited effect on the antiplatelet effect of prasugrel.

Grapefruit Juice Inhibits the Metabolic Activation of Clopidogrel

Cytochrome P450 (CYP) enzymes, including CYP2C19 and CYP3A4, participate in the bioactivation of clopidogrel. Grapefruit juice constituents potently inactivate intestinal CYP3A4 and have been shown to inhibit CYP2C19 as well. In a randomized crossover study, 14 healthy volunteers ingested 200 ml of grapefruit juice or water three times daily for 3 days. On day 3, they ingested a single 600-mg dose of clopidogrel. Grapefruit juice reduced the peak plasma concentration (Cmax) of the active metabolite of clopidogrel to 13% of the control (range 11-17%, P < 0.001) and the area under the plasma concentration-time curve from 0 to 3 h to 14% (range 12-17%, P < 0.001) of the control, but it had no significant effect on the parent clopidogrel. Moreover, grapefruit juice markedly decreased the platelet-inhibitory effect of clopidogrel, as assessed with the VerifyNow P2Y12 test in two of the participants. In conclusion, concomitant use of grapefruit juice may impair the efficacy of clopidogrel. Therefore, the use of grapefruit juice is best avoided during clopidogrel therapy.

Grapefruit juice markedly increases the plasma concentrations and antiplatelet effects of ticagrelor in healthy subjects

This study examined the effects of grapefruit juice on the new P2Y12 inhibitor ticagrelor, which is a substrate of CYP3A4 and P-glycoprotein. In a randomized crossover study, 10 healthy volunteers ingested 200 ml of grapefruit juice or water thrice daily for 4 days. On day 3, they ingested a single 90 mg dose of ticagrelor. Grapefruit juice increased ticagrelor geometric mean peak plasma concentration (Cmax ) to 165% (95% confidence interval 147, 184%) and area under the concentration-time curve (AUC(0,∞)) to 221% of control (95% confidence interval 200, 245%). The Cmax and AUC(0,34 h) (P < 0.05) but not the AUC(0,∞) of the active metabolite C12490XX were decreased significantly. Grapefruit juice had a minor effect on ticagrelor elimination half-life prolonging it from 6.7 to 7.2 h (P = 0.036). In good correlation with the elevated plasma ticagrelor concentrations, grapefruit juice enhanced the antiplatelet effect of ticagrelor, assessed with VerifyNow® and Multiplate® methods, and postponed the recovery of platelet reactivity. Grapefruit juice increased ticagrelor exposure by more than two-fold, leading to an enhanced and prolonged ticagrelor antiplatelet effect. The grapefruit juice-ticagrelor interaction seems clinically important and indicates the significance of intestinal metabolism to ticagrelor pharmacokinetics.

Grapefruit Juice Enhances the Exposure to Oral Oxycodone

Grapefruit juice alters the concentrations of many CYP3A substrates. The objective of this study was to examine the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral oxycodone in a randomized cross-over study with two phases at an interval of 4 weeks. Twelve healthy volunteers ingested 200 ml of grapefruit juice or water t.i.d. for 5 days. An oral dose of oxycodone hydrochloride 10 mg was administered on day 4. Oxycodone, noroxycodone, oxymorphone and noroxymorphone concentrations were analysed from the plasma samples for 48 hr and behavioural and analgesic effects were recorded for 12 hr. Grapefruit juice increased the mean area under the oxycodone concentration-time curve (AUC(0-∞) ) by 1.7-fold (p<0.001), the peak plasma concentration by 1.5-fold (p<0.001) and the half-life of oxycodone by 1.2-fold (p<0.001) as compared to the water. The metabolite-to-parent AUC(0-∞) ratios (AUC(m)/AUC(p) ) of noroxycodone and noroxymorphone decreased by 44% (p<0.001) and 45% (p<0.001), respectively. Oxymorphone AUC(0-∞) increased by 1.6-fold (p<0.01) after grapefruit juice, but the AUC(m)/AUC(p) remained unchanged. Pharmacodynamic changes were modest and only self-reported performance significantly impaired after grapefruit juice. Analgesic effects were not influenced. Grapefruit juice inhibited the CYP3A4-mediated first-pass metabolism of oxycodone, decreased the formation of noroxycodone and noroxymorphone and increased that of oxymorphone. We conclude that dietary consumption of grapefruit products may increase the concentrations and effects of oxycodone in clinical use.

Grapefruit Juice Greatly Reduces the Plasma Concentrations of the OATP2B1 and CYP3A4 Substrate Aliskiren

In a randomized crossover study, 11 healthy volunteers ingested 200 ml of grapefruit juice or water three times a day for 5 days. On day 3, they ingested a single 150-mg dose of aliskiren. Grapefruit juice reduced aliskiren peak plasma concentration (C(max)) by 81% (range, 42-91%, P < 0.001), area under the plasma aliskiren concentration-time curve (AUC)(0-infinity) by 61% (range, 15-72%, P < 0.001), and elimination half-life (t(1/2)) from 26.1 to 23.6 h (P = 0.020). Therefore, concomitant use of aliskiren and grapefruit juice is best avoided.

Grapefruit juice, lyophilized grapefruit juice, and powdered whole grapefruit inhibit cytochrome P450-mediated triazolam hydroxylation by beagle dog liver microsomes

Coadministration of grapefruit juice (GFJ) has been proposed to enhance the systemic availability and decrease the required dose of drugs such as cyclosporine that are extensively metabolized in the intestine and liver. Although GFJ inhibits human cytochrome P450 (CYP) 3A, effects on dog CYP have not yet been reported. Consequently, we determined whether GFJ inhibits triazolam hydroxylation by Beagle dog liver microsomes (DLM) using human liver microsomes (HLM) as positive control. Results were compared with the effects of lyophilized GFJ and commercially-available powdered grapefruit capsules, which may be more convenient dosage forms. GFJ inhibited alpha-hydroxytriazolam formation in both DLM and HLM with similar IC(50) (inhibitor concentration producing a 50% decrease in reaction velocity) values of 0.56% and 0.52% (v/v), respectively. Lyophilized GFJ and powdered grapefruit also inhibited DLM alpha-hydroxytriazolam formation with IC(50) values of 0.76 and 1.2 mg/mL, respectively. Consistent with mechanism-based enzyme inhibition, preincubation of DLM with any of the grapefruit products for 20 min resulted in significant enhancement of inhibition of triazolam alpha-hydroxylation by 8-20%. The results indicate that 16 g of lyophilized GFJ or 23 g of powdered grapefruit would be equivalent to dosing 100 mL of GFJ. In vivo pharmacokinetic interaction studies are needed to confirm these in vitro findings.

Grapefruit juice alters plasma sertraline levels after single ingestion of sertraline in healthy volunteers

Objective. Grapefruit juice contains a number of natural substances that have the capacity to inhibit the activity of human cytochrome P450 (CYP) 3A4, CYP1A2, and p-glycoprotein. We investigated the effects of grapefruit juice on the pharmacokinetics of sertraline in healthy volunteers. Methods. Eight healthy subjects volunteered for the study after providing written informed consent to participate. The study used a crossover design with two phases separated by an interval of at least 2 weeks. The subjects ingested 250 ml of grapefruit juice or 250 ml of water 3 times daily for 5 days. On day 6, each subject was given 75 mg of sertraline with 250 ml of grapefruit juice or water. Blood samples were taken 2, 4, 6, 8, 10, 24, and 48 h later. Plasma levels of sertraline were determined by high-performance liquid chromatography. Results. Grapefruit juice increased the mean peak concentrations in plasma (Cmax) of sertraline from 17.6±6.1 to 29.3±11.5 ng/ml (mean±SD, P=0.003) and the mean area under the plasma sertraline concentration–time curve (AUC) from 0 to ∞ of sertraline from 402.0±151.9 to 820.5±313.0 h ng/ml (mean±SD, P=0.002). Conclusion. These results suggest that grapefruit juice affects the pharmacokinetics of sertraline.

The Use of Heat Treatment to Eliminate Drug Interactions Due to Grapefruit Juice

Grapefruit juice (GJ) contains components that may increase the bioavailability of drugs; however, approaches to the removal of these components have been little investigated. It is known that furanocoumarin derivatives (FCs), such as bergamottin (BG) and 6',7'-dihydroxybergamottin (DHB) in GJ, induce such drug interactions. In the present study, it was found that the heat treatment of grapefruit juice decreases concentrations of BG and DHB as well as their interactions both in vitro and in vivo. We incubated GJ for 10, 20, 30, 40, 50, and 60 min at 37, 62, 72, and 95 degrees C; FCs in each sample were then measured, using high-performance liquid chromatography (HPLC). The concentrations of BG and DHB were decreased in a time- and temperature-dependent manner, by 82.5 and 97.9% respectively, after incubation for 1 h at 95 degrees C. In contrast, the concentration of bergaptrol (BT) increased in a time- and temperature-dependent manner (27.7% after 60 min at 95 degrees C). In addition, the effect of each GJ sample on testosterone 6beta-oxidation in human liver microsomes was observed. The inhibitory effects of GJ heated to 95 degrees C were decreased in a time-dependent manner, as in the case of BG and DHB concentrations. Furthermore, 2 ml of GJ treated for 60 min at 95 degrees C was administered into the rat duodenum. After 30 min, nifedipine (NFP) was administered intraduodenally at a dose of 3 mg/kg body weight. The concentrations of NFP in the plasma samples were determined by HPLC. No significant increase in the AUC of NFP was observed in the rats given heat-treated GJ. These results suggest that the heat treatment of GJ reduces the concentrations of FCs, thus eliminating the potential for drug interactions.

A reply:

In their letter to the editor, Josefsson & Ahlner correctly admit that grapefruit juice has no appreciable effect on the pharmacokinetics and pharmacodynamics of amlodipine. However, they argue that in their paper [1], Cmax as well as AUC were significantly (P < 0.05) higher when 5 mg amlodipine was administered with 250 ml of grapefruit juice compared with when administered with water. They claim that variability in the pharmacokinetics of amlodipine rather than variability due to analytical methods underlie the differences in the conclusions from their paper compared with the results from our study [2], although they did not indicate the confidence intervals of the ratios of their Cmax and AUC. In addition, Josefsson & Ahlner claim that whereas they showed data from all their subjects, we excluded one half of our subjects and implicitly skewed our results. While pharmacokinetic variations due to biological factors are feasible, the magnitude of the mean absolute bioavailability for amlodipine reported in our study is in agreement with data reported independently by Abernethy et al.[3], as well as data on file from a study in mildly hypertensive patients. With an absolute bioavailability > 80%, bioavailability enhancement as described for calcium channel blockers with a high first-pass metabolism when grapefruit juice is concurrently administered is unlikely to be significant with amlodipine, even if one assumes complete absorption. There is a correlation between blood pressure fall and plasma concentrations of calcium channel blockers [4–6], including amlodipine [3]. In studies with felodipine and nisoldipine, significant changes in exposure following concurrent administration of grapefruit juice were accompanied by changes in haemodynamics [7, 8]. The absence of any change in blood pressure or heart rate in their study is therefore consistent with the absence of any meaningful changes in blood concentrations of amlodipine. The assertion that we excluded subjects in our analysis is a complete misrepresentation of our paper. Pharmacokinetic and pharmacodynamic data from all 20 subjects were used in the analyses of both the oral and intravenous arms of the data on unresolved amlodipine. Plasma samples collected during our study were assayed for unresolved amlodipine prior to enantiomer assays being run. In a few subjects, the volume of plasma was inadequate at all time points for the enantiomer assays. We correctly identified all such data in our manuscript. We believe that the conclusions from our study have not been compromised because of the missing enantiomer data, recognizing the consistency of the data shown. There were also substantial differences between the conditions and design of our study and the study reported by Josefsson & Ahlner. We used a larger sample size of 20 subjects compared with their 12 subjects. We also used a higher dose of amlodipine (10 vs 5 mg), to ensure a more appropriate characterization of plasma concentrations over a longer interval. In our study, grapefruit juice was administered with amlodipine on the day of dosing and repeated daily with breakfast for the 9 days during which blood samples were obtained for pharmacokinetics. This profile more clearly mimics real life situations for subjects who routinely drink grapefruit juice with breakfast when medications are commonly consumed. In addition, the conditions of our study would more readily demonstrate any potential interaction, recognizing that grapefruit juice was on board continuously. Finally, we studied both oral and intravenous amlodipine to more appropriately define its pharmacokinetics under the conditions of our study. The results with both formulations were consistent for both unresolved amlodipine and the enantiomers. In conclusion, while it may be argued that normal biological variability could influence the pharmacokinetic data shown in these studies, it is unfortunate that Josefsson & Ahlner misrepresented our data in their letter. We agree with the conclusion in their paper that grapefruit juice does not alter the pharmacokinetics and pharmacodynamics of amlodipine.

Influence of low-dose oral contraceptives, alcohol, and grapefruit on.

The aminopryine breath test (ABT) measures hepatic reserve in patients with acute and chronic liver disease and gives an assesment of the hepatic function in patients undergoing major liver surgery. Aminopyrine is metabolized by the mixed cytochrome P-450 system, which can be influenced by many foreign compounds and drugs. Whether these foreign compounds and drugs can influence the results of the ABT has seldomly been tested. We studied three groups: Healthy female volunteers, either normally menstruating or taking oral contraceptives, were asked to perform a [13C]ABT during the time of the menses and at midcylce. Healthy volunteers were asked to perform a ABT after consuming 30 g of alcohol. Healthy volunteers were asked to perform a ABT after consuming 250 ml of grapefruit juice. The 13C/12C ratio in expired air was measured by gas isotope ratio mass spectrometry.

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.

The effect of paracetamol on peritoneal reflex after single and multiple grapefruit ingestion

In the last few years, more attention has been paid to the influence of grapefruit juice on metabolism on many drugs. It has been reported that grapefruit juice increases the plasma concentrations of orally administrated drugs, that undergo metabolism in liver. 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 could also cause these effects. Paracetamol is metabolized by reactions of oxidation and conjugation to nontoxic ineffective metabolites. These reactions, partly catalyzed by cytochrome P450 izoenzymes, take place in liver. The analgesic effect of paracetamol was examined by Writhing tests, where we used acetic acid as an irritating agent. We used three groups of male mice: the control group, the group which was administrated 0.2 mL of grapefruit juice per os 10 days (GPOch) and the group which was administrated single dose of 0.5 mL grapefruit juice per os 90 min. before the experiment (GPOac). Dose of 50 mg/kg of paracetamol was applicated s.c. 5 min. before i.p. application of 3 % acetic acid. The writhing phenomenon was observed in periods of 5-15 min. and 15-30 min. after the application of paracetamol. The results show that paracetamol in GPOch group significantly decreases irritant effect of acetic acid in the period of 15-30 min. after the application in relation to the control group. However, the acetic acid shows stronger irritant effect in GPOch group than in the control group and less irritant effect in GPOac group than in the control group. In the period of 5-15 min. after the application, paracetamol shows analgesic effect neither in the control nor in the other groups.