Antioxidant activity of Paraguayan plant extracts.

The antioxidant properties of six medical herbs used in the traditional Paraguayan medicine were studied using free radical-generating systems. The methanol extracts from Aristolochia giberti, Cecropia pachystachya, Eugenia uniflora, Piper fulvescens, Schinus weinmannifolia and Schinus terebinthifolia protected against enzymatic and non-enzymatic lipid peroxidation in microsomal membranes of rat. C. pachystachya, E. uniflora, S. weinmannifolia and S. terebinthifolia showed the highest scavenging activity on the superoxide and DPPH radicals.

Effect of physical activity on the pharmacokinetics of ceftazidime in mice.

BACKGROUND: The aim of the present work was to assess comparatively the pharmacokinetic profile of ceftazidime (CAZ) in trained and non-trained mice. METHODS: The study was performed on 256 mice divided at random into four groups: long-term physically trained mice with (E1a) and without (E1b) physical activity prior to the administration of CAZ, and untrained mice with (E2a) and without (E2b) physical activity prior to the administration of the antibiotic. CAZ was administered intramuscularly (25 mg/kg) to all mice, and blood samples were obtained at different time points. The plasma concentrations of CAZ were determined by HPLC and analyzed by non-compartmental models. RESULTS: The area under the curves in groups E1a and E2a (27.3 and 22.9 microg x ml(-1) x h, respectively) were different compared to the other groups [(E1b) = 11.1 and (E2b) = 15.6 microg x ml(-1) x h; p < 0.05]. Differences were observed between the concentration-time of CAZ in E1a compared to E1b, E1a versus E2a, E1a versus E2b, E1b versus E2a and E1b versus E2b (p < 0.05). CONCLUSION: Physical activity performed prior to CAZ administration modified the pharmacokinetic profile of the drug administered to mice.

Antioxidant activity of anti-inflammatory plant extracts.

The antioxidant properties of twenty medical herbs used in the traditional Mediterranean and Chinese medicine were studied. Extracts from Forsythia suspensa, Helichrysum italicum, Scrophularia auriculata, Inula viscosa, Coptis chinensis, Poria cocos and Scutellaria baicalensis had previously shown anti-inflammatory activity in different experimental models. Using free radical-generating systems H. italicum. I. viscosa and F. suspensa protected against enzymatic and non-enzymatic lipid peroxidation in model membranes and also showed scavenging property on the superoxide radical. All extracts were assayed at a concentration of 100 microg/ml. Most of the extracts were weak scavengers of the hydroxyl radical and C. chinensis and P. cocos exhibited the highest scavenging activity. Although S. baicalensis inhibited the lipid peroxidation in rat liver microsomes and red blood cells, the extract showed inhibitory actions on aminopyrine N-demethylase and xanthine oxidase activities as well as an pro-oxidant effect observed in the Fe3+-EDTA-H2O2 system. The results of the present work suggest that the anti-inflammatory activities of the same extracts could be explained, at least in part, by their antioxidant properties.

Pharmacokinetics and penetration into tissue fluid of ceftizoxime in normal and hyperthermic sheep.

The pharmacokinetics of ceftizoxime was studied in six sheep before and after inducing hyperthermia using Escherichia coli endotoxin. Sheep implanted subcutaneously with cages of non-reactive material for collecting tissue cage fluid (TCF) were used to conduct two trials. In Trial 1 animals with normal basal temperature (normal sheep (NS)) were given intravenous (i.v.) and intramuscular (i.m.) monodoses of ceftizoxime (20mg/kg BW) at 1 week interval. One and 5 weeks later (Trial 2) each sheep were injected 1µg/kg BW of endotoxin to produce hyperthermia (hyperthermic sheep (HS)) previously to i.v. administration (HSi.v.) and i.m. (HSi.m.) of ceftizoxime (20mg/kg BW), respectively. Serum and TCF samples were collected over 6h post-administration. Ceftizoxime concentrations in serum and TCF were determined by a microbiological assay. The concentrations in serum and TCF of ceftizoxime were analyzed through compartmental and non-compartmental models.Rectal temperature were significantly incremented in all animals during Trial 2. The half-time and constant of elimination in serum of ceftizoxime in NSi.v. (t(1/2)=1.1+/-0.4h; lambda(z)=0.7+/-0.2h(-1)) were statistically different those observed in HSi.v. (t(1/2)=1.4+/-0.4h; lambda(z)=0.5+/-0.2h(-1)). The constants of distribution in NSi.v. and HSIV were 5.1+/-4.6 and 4.1+/-3.4h(-1), respectively. The time to reach the maximum concentrations in TCF was latter (p<0.05) in NS (t(max)=2.3+/-0.7h) than in HS (t(max)=1.3+/-0.6 h). After i.m. administration in NS the absorption half-life (0.12+/-0.19h) was latter (p<0.05) than in HS (0.06+/-0.007h) with greater areas under the curve (AUC in NS=65.4+/-20.8 and AUC in HS=34.7+/-7.5 (µg/ml) h). The maximum value of concentration in serum (C(max)) and AUC in TCF were greater (p<0.05) in NS (C(max)=46.1+/-10.6µg/ml and AUC=84.4+/-17.4 (µg/ml) h) as compared to same HS (C(max)=27.0+/-12.9µg/ml and AUC=47.9+/-3.9 (µg/ml) h). The concentrations of ceftizoxime in TCF after i.v. and i.m. in NS and HS were elevated during a 6h period after administration. The bioavailability of ceftizoxime in NS (101.6+/-59.9%) and HS (87.4+/-63.3%) was suitable for its use by the i.m. route.

Antioxidant effects of an aqueous extract of Ilex paraguariensis.

In this work we investigate the antioxidant properties of an aqueous extract prepared from an infusion of Ilex paraguariensis (Aquifoliaceae) using free radical-generating systems. The extract inhibited the enzymatic and nonenzymatic lipid peroxidation in rat liver microsomes in a concentration-dependent fashion, with IC(50) values of 18 microg/ml and 28 microg/ml, respectively. The extract also inhibited the H(2)O(2)-induced peroxidation of red blood cell membranes with an IC(50) of 100 microg/ml and exhibited radical scavenging properties toward superoxide anion (IC(50) = 15 microg/ml) and 2,2-diphenyl-1-picrylhydrazyl radical. In the range of concentrations used, the extract was not a scavenger of the hydroxyl radical. Our results suggest that ingestion of extracts of Ilex paraguariensis could contribute to increase the antioxidant defense of an organism against free radicals attack.

Effect of the chloroform extract of Tanacetum vulgare and one of its active principles, parthenolide, on experimental gastric ulcer in rats.

This study examines the anti-ulcerogenic activity of a chloroform extract of Tanacetum vulgare and purified parthenolide, the major sesquiterpene lactone found in the extract. Gastric ulcers induced by oral administration of absolute ethanol to rats were reduced dose-dependently by oral pretreatment of animals with the chloroform extract (2.5-80 mg kg(-1)) or parthenolide (5-40 mg kg(-1)). When administered 30 min before challenge with the alcohol the protection ranged between 34 and 100% for the extract and 27 and 100% for parthenolide. When the products were administered orally 24 h before treatment with ethanol, 40 mg kg(-1) of the extract and of the lactone reduced the mean ulcer index from 4.8+/-0.3 for control animals to 1.4+/-0.2 and 0.5+/-0.1, respectively. The products also prevented alcohol-induced reduction of the number of sulphydryl groups within the gastric mucosa (50.6+/-2.3 microg (mgprotein)(-1) for normal animals compared with 17.7+/-3.0 microg (mg protein)(-1) for alcohol-treated animals). Administration of the extract (80 mg kg(-1)) or parthenolide (40 mg kg(-1)) 24 h before ethanol treatment restored the numbers of mucosal -SH groups to values near those found for normal animals. These results suggest that the products assayed, in particular parthenolide, might find therapeutic application, although further work is required to establish their profit/risk ratio.

Anti-inflammatory effects of South American Tanacetum vulgare.

In recent years the role of phenolic compounds and sesquiterpene lactones, particularly parthenolide, in the anti-migraine and anti-inflammatory effects of Tanacetum parthenium (Asteraceae) has attracted much attention. However, the closely-related cosmopolitan species T. vulgare has remained outside the mainstream of research in this field. After treating the aerial parts of T. vulgare with dichloromethane and methanol, and applying conventional column and thin-layer chromatographic techniques, it was possible to isolate from the moderately lipophilic fractions the principles responsible for the anti-inflammatory activity of this plant against the mouse-ear oedema induced by 12-O-tetradecanoylphorbol 13-acetate. These were identified by ultraviolet and nuclear magnetic resonance spectroscopy as parthenolide (93% oedema inhibition at 0.5 mg/ear, ID50 (dose of drug inhibiting the oedema by 50%) = 0.18 micromol/ear) and the methoxyflavones jaceosidin (80% oedema inhibition at 0.5 mg/ear, ID50 = 0.50 micromol/ear), eupatorin, chrysoeriol and diosmetin. Because in molar terms the potency of parthenolide was nearly three times greater than that of the most active of the flavones and because it is obtained from the plant in considerably larger amounts, the flavonoids must only be partially responsible, and to a minor extent, for the observed in-vivo anti-inflammatory local effect.

Effect of arsenic (V) on the antioxidant defense system: in vitro oxidation of rat plasma lipoprotein.

Adult male rats were treated orally with sodium arsenate (10 mg As/kd/day) for 2 days, and in increase in hepatic glutathione level was seen. Ascorbic acid content increased in both liver and plasma of intoxicated animals. Hepatic activities of superoxide dismutase and glutathione peroxidase did not change with the treatment and there was no increase in the level of lipid peroxidation measured as thiobarbituric acid-reacting substances (TBARS). Arsenic decreased the plasma level of uric acid and increased the plasma triglycerides content without modifying vitamin E levels. Both total lipoproteins and very low density lipoprotein plus low density lipoprotein (VLDL + LDL) fractions demonstrated greater propensity for in vitro oxidation than the corresponding untreated rats. The last finding might be a useful parameter for determining the degree of oxidative stress in the initial steps of intoxication with arsenic.

The pharmacokinetics of ceftazidime in lactating and non-lactating cows.

The pharmacokinetics of ceftazidime (CAZ) were studied in lactating (LTG) and non-lactating (NLTG) cows. Two groups (LTG and NLTG) of 5 healthy dairy cows were given ceftazidime (10 mg/ kg body weight) intravenously (i.v.) and intramuscularly (i.m.). Serum and milk (LTG) and serum samples (NLTG) were collected over a 24-h period post-administration. CAZ concentrations in serum and milk were determined by high-performance liquid chromatography, and an interactive and weighted-non-linear least-squares regression analysis was used to perform the pharmacokinetic analysis. The pharmacokinetic profiles in LTG and NLTG cows which had received CAZ i.v. fitted a three-compartment model and a two-compartment model, respectively. The CAZ concentration-time curves in serum and the area under the curve were greater and more sustained (p < 0.05) in the LTG cows by both routes, while the serum clearance (Cls = 72.5 +/- 18.1 ml/h per kg) was lower (p < 0.05) than that in the NLTG cows (Cls = 185.9 +/- 44.2 ml/h per kg). CAZ given i.v. exhibited a relatively long half-life of elimination (t1/2 beta (LTG) = 1.1 +/- 0.2 h; t1/2 beta (NLTG) = 1.4 +/- 0.3 h). Compared with other cephalosporins, CAZ had good penetration into the mammary gland (47.7 +/- 38.2% for CAZ i.v.; 51.1 +/- 39.0% for CAZ i.m.). Finally, the bioavailability of CAZ (F(LTG) = 98.9 +/- 36.8%; F(NLTG) = 77.1 +/- 25.3%) was suitable for its used by the i.m. route in lactating and non-lactating cows.

Pharmacokinetics and penetration into tissue fluid of cefotaxime in bovines.

Concentrations of cefotaxime in serum and tissue fluid were studied in the bovine after intravenous and intramuscular administration at a dosage of 10 mg.kg-1 body weight. Steers implanted subcutaneously with tissue cages were used. After intravenous bolus administration, profiles of mean concentrations in serum over time were described by a two-compartment open model. The rate constant of elimination was 1.4 +/- 0.3 h-1 and the half-life 0.6 +/- 0.1 h. The rate constant of distribution was 11.5 +/- 1.9 h-1, and the half-life was 0.06 +/- 0.01 h. The volume of distribution at steady state was 250.6 +/- 37.3 ml.kg-1. The area under the curve was 31.8 +/- 7.4 micrograms.ml-1.h. The penetration ratio into tissue fluid was 36.5 +/- 15.4%. After intramuscular injection, the half-life was 1.1 +/- 0.3 h, the area under the curve was 27.5 +/- 6.8 micrograms.ml-1.h, and the penetration ratio into tissue fluid was 47.1 +/- 15.8%. The concentrations in tissue fluid after intravenous and intramuscular administration of cefotaxime were elevated during a 6-hour period after administration.