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Emodin reverses CCl4 induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural changes: The in vivo evidence

Monika Bhadauria
Aim:, The curative effect of emodin (1,3,8-trihydroxy-6-methyl anthraquinone), an active compound of the plant species Ventilago maderaspatana Gaertn, was evaluated against carbon tetrachloride (CCl4) induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural alterations in rats. Methods:, Female rats were administered CCl4 (1.5 mL/kg, ip) followed by varying doses of emodin (20, 30 and 40 mg/kg, oral po) after 24 h of CCl4 administration. Animals were euthanized after 24 h of last administration to determine liver function tests in serum, hepatic light microscopic and ultrastructural changes, activity of CYP enzymes, microsomal lipid peroxidation and protein contents, hexobarbitone induced sleep time and bromosulphalein retention. Results:, The CCl4 induced-toxic effects were observed with sharp elevation in the release of serum transaminases, alkaline phosphatase, lactate dehydrogenase and ,-glutamyl transpeptidase. An initial study for an optimum dose of emodin among different dose levels revealed that a 30 mg/kg dose was effective in restoring all the enzymatic variables and liver histoarchitecture in a dose dependent manner. Exposure to CCl4 diminished the activities of CYP enzymes (i.e. aniline hydroxylase and amidopyrine-N-demethylase and microsomal protein contents with concomitant increase in microsomal lipid peroxidation). Emodin at 30 mg/kg effectively reversed the CCl4 induced hepatotoxic events, which was consistent with ultrastructural observations. Hexobarbitone-induced sleep time and plasma bromosulphalein retention also improved liver functions after emodin therapy. Conclusion:, By reversal CYP activity and ultrastructural changes, emodin shows a strong hepatoprotective abilities. [source]

Clenbuterol in the horse: urinary concentrations determined by ELISA and GC/MS after clinical doses

J. D. Harkins
Clenbuterol is a ,2 agonist/antagonist bronchodilator marketed as Ventipulmin® and is the only member of this group of drugs approved by the US Food and Drug Administration (FDA) for use in horses. Clenbuterol is a class 3 drug in the Association of Racing Commissioners International (ARCI) classification system; therefore, its identification in postrace samples may lead to sanctions. Recently, the sensitivity of postrace testing for clenbuterol has been substantially increased. The objective of this study was to determine the ,detection times' for clenbuterol after administration of an oral clinical dose (0.8 g/kg, b.i.d.) of Ventipulmin syrup. Five horses received oral clenbuterol (0.8 g/kg, b.i.d.) for 10 days, and urine concentrations of clenbuterol were determined by an enhanced enzyme-linked immunoabsorbent assay (ELISA) test and gas chromatography/mass spectrometric (GC/MS) analysis by two different methods for 30 days after administration. Twenty-four hours after the last administration, urine concentrations of apparent clenbuterol, as measured by ELISA, averaged about 500 ng/mL, dropping to about 1 ng/mL by day 5 posttreatment. However, there was a later transient increase in the mean concentrations of apparent clenbuterol in urine, peaking at 7 ng/mL on day 10 postadministration. The urine samples were also analysed using mass spectral quantification of both the trimethylsilyl (TMS) and methane boronic acid (MBA) derivatives of clenbuterol. Analysis using the TMS method showed that, at 24 h after the last administration, the mean concentration of recovered clenbuterol was about 22 ng/mL. Thereafter, clenbuterol concentrations fell below the limit of detection of the TMS-method by day 5 after administration but became transiently detectable again at day 10, with a mean concentration of about 1 ng/mL. Derivatization with MBA offers significant advantages over TMS for the mass spectral detection of clenbuterol, primarily because MBA derivatization yields a high molecular weight base peak of 243 m/z, which is ideal for quantitative purposes. Therefore, mass spectral analyses of selected urine samples, including the transient peak on day 10, were repeated using MBA derivatization, and comparable results were obtained. The results show that clenbuterol was undetectable in horse urine by day 5 after administration. However, an unexpected secondary peak of clenbuterol was observed at day 10 after administration that averaged ,1 ng/mL. Because of this secondary peak, the detection time for clenbuterol (0.8 g/kg, b.i.d. × 10 days) is at least 11 days if the threshold for detection is set at 1 ng/mL. [source]

Evaluation of antioxidant activity of Ginkgo biloba phytosomes in rat brain

Suresh R. Naik
Abstract Ginkgo biloba from the traditional Chinese system of medicine has been found to possess neurocognitive enhancing effects. The mechanism of action of Ginkgo seems to be related to its antioxidant properties. In the present study, Ginkgo biloba phytosomes were administered to Wistar rats at 50 mg/kg and 100 mg/kg for 7 and 14 days. Chemical hypoxia was induced by administration of sodium nitrite (75 mg/kg) 1 h after the last administration of treatment. Thirty minutes after sodium nitrite administration, the animals were killed and the cerebral cortex, cerebellum, hippocampus and striatum were isolated and homogenized. The supernatants were used for the estimation of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Ginkgo biloba phytosome treatment was found to increase superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities in all the brain regions compared with those treated only with sodium nitrite. The prevention of depletion of the antioxidant enzymes by sodium nitrite in the presence of Ginkgo biloba phytosomes may be correlated to its antioxidant activity. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Four-year study of controlled timed breeding of rhesus monkeys (Macaca mulatta)

Kathrine Phillippi-Falkenstein
Abstract As part of the timed breeding colony at Tulane National Primate Research Center, exogenous progesterone administration (5 mg/day for 10 days) has been used to select conception dates by inducing artificial luteal phases in female rhesus monkeys. A retrospective analysis of data obtained during four breeding seasons (1998,2001) revealed that conceptions occurred an average of 18 days after the last administration of progesterone. The age of the female to be bred, previous pregnancy history, and timing of breeding during the breeding season were determined to be critical factors in the success of the procedure. The benefit of this method of timed breeding is that it does not require tracking of menstrual cycles, which can be labor-intensive and requires that animals be monitored several months in advance of breeding to determine each female's individual cycle length. It also provided an efficient use of breeding-age males. Am. J. Primatol. 60:23,28, 2003. © 2003 Wiley-Liss, Inc. [source]

Effects of Subchronic Lithium Treatment on Levels of BDNF, Bcl-2 and Phospho-CREB in the Rat Hippocampus

Michael D. Hammonds
Few studies have examined the effects of lithium exposure on the regulation of these molecules in the dentate gyrus (DG) and area CA1 in the hippocampus. We examined the effects of subchronic lithium treatment on the levels of BDNF, Bcl-2 and phosphorylated CREB in the DG and area CA1. We administered LiCl intraperitoneally (1 mEq/kg per day) to adult rats for 14 days, killed animals in 24 hr after the last administration of the drug, and determined the tissue levels of BDNF, Bcl-2 and pCREB in the DG and area CA1. Subchronic lithium treatment for 14 days did not significantly alter the levels of BDNF, Bcl-2 or phosphorylated CREB in the DG and area CA1 in the hippocampus. This study indicates that the lithium-induced up-regulation of these molecules may be various depending on the duration of lithium exposure and particular brain regions exposed to the drug. [source]

The role of Lactobacillus casei rhamnosus Lcr35 in restoring the normal vaginal flora after antibiotic treatment of bacterial vaginosis

L Petricevic
Objective, To evaluate the efficacy of additional topical Lactobacillus casei rhamnosus (Lcr35) subsequent to antibiotic treatment of bacterial vaginosis (BV) to restore the normal vaginal flora. Study design, Single-centre, randomised, observerblinded study. Setting, Population-based study in Vienna over 1 year. Sample, 190 women were enrolled in the study. Methods, Women with Nugent scores between 7 and 10 on initial vaginal swab were randomised to the one of two groups. All women were treated with standard antibiotic therapy for 7 days. Only women in the intervention group received vaginal capsules containing 109 colony-forming units of live Lcr35 for 7 days after antibiotic treatment. Final vaginal swabs for Nugent scoring were taken 4 weeks after the last administration of the study medication. Main outcome measures, The primary efficacy variable was a change in the Nugent score between the baseline and the end of the study of at least 5 grades in each individual woman. Results, Sixty-nine of the 83 women (83%) in the intervention group and 31 of the 88 women (35%) in the control group showed a reduction of the Nugent score by at least 5 grades. The difference in the number of women with improvement was highly significant (P < 0.001). The median difference in Nugent scores between initial and final swabs was 6.61 in the intervention group and 4.13 in the control group (P < 0.001). Conclusion, Our data show that the restoration of the vaginal flora after antibiotic treatment of BV can be significantly enhanced by exogenously applied lactobacilli. [source]

Thalidomide for the Treatment of Refractory Multiple Myeloma: Association of Plasma Concentrations of Thalidomide and Angiogenic Growth Factors with Clinical Outcome

CANCER SCIENCE, Issue 9 2002
Tsunayuki Kakimoto
Recent reports showed that thalidomide has anti-angiogenic activity and is effective for the treatment of refractory multiple myeloma (MM). We examined the relationship between the clinical efficacy and adverse effects of thalidomide and the plasma concentrations of this drug as well as angiogenic growth factors in refractory MM. Ten out of twenty-four evaluable patients (42%) showed more than 25% reduction of M-protein, and eight (33%) achieved more than 50% reduction. These changes were associated with restoration of anemia and recovery of normal immunoglobulin level. Somnolence and headache, constipation, peripheral neuropathy and skin rash were frequently observed, but were well tolerated. However, grade 2,4 severe neutropenia was also observed in nine cases. These adverse effects other than neutropenia occurred more frequently in the patients with higher plasma concentrations of thalidomide (,2.0 ,g/ml at 12 h after the last administration) and were readily alleviated by dose reduction. In contrast, neutropenia developed regardless of the plasma concentration. Plasma concentrations of angiogenic growth factors were frequently elevated before treatment. After thalidomide treatment, these growth factor levels tend to decrease to near-normal ranges in responders but were still high in most non-responders. After thalidomide treatment, plasma vascular endothelial growth factor (VEGF) level was significantly reduced in responders (P=0.025), but not in non-responders (P=0.37). Reduction of plasma VEGF level might be an important indicator for anti-myeloma effect of thalidomide. [source]