An effect of phenobarbitone on griseofulvin metabolism in the rat

Prior administration of phenobarbitone to male and female rats dosed orally or intravenously with griseofulvin caused a fall in blood levels of the antibiotic. The effect of a single oral dose of phenobarbitone was significant after 12 hr and maximal between 12 and 48 hr, and it lasted for at least 96 hr; it was more pronounced when the barbiturate was administered repeatedly. Liver slices from animals dosed with phenobarbitone metabolized griseofulvin more rapidly than did those from undosed animals. The possible relevance of these findings to the clinical use of griseofulvin is discussed.     

Effect of valproic acid on zinc metabolism in the rat

Previous studies have suggested that the mechanism of valproic acid (VPA) hepatotoxicity may involve a drug-induced Zn deficiency. To test this hypothesis, the uptake of 65Zn or tissue Zn concentration was determined in plasma, liver, bone, kidney, and brain of adult male rats, administered parenteral VPA according to one of 3 schedules: 750 mg/kg; 500 mg/kg; and 100 mg/kg/day X 7 days. Histopathological changes in liver and weight loss were observed in rats 5 days after administration of VPA (750 mg/kg). The plasma Zn level in VPA toxic rats was significantly depressed compared to saline-injected controls, although the Zn content of liver and bone was unaffected. Furthermore, tissue uptake of 65Zn was not altered in rats 6 h after receiving VPA 500 mg/kg or after chronic administration at 100 mg/kg/day. On the basis of the present study, there is no evidence that Zn deficiency is induced by hepatotoxic doses of VPA in rats.     

Effect of folic acid supplementation on oxidative gastric mucosa damage and acid secretory response in the rat

Objective:

This study investigated the antioxidative and antisecretory properties of folic acid in the rats’ stomach.

Materials and Methods:

Male Wistar rats were treated with 2 mg/kg diet of folic acid for 21 days. Gastric ulceration was induced by indomethacin, scored, and assayed to determine the concentration of total protein, mucus, malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) in homogenized samples. Normal saline and Ranitidine treated group served as negative and positive control, respectively. Basal and stimulated acid secretion was measured by continuous perfusion method.

Result:

Indomethacin caused severe damage to the rats’ stomach with an ulcer index of 4.32 ± 0.13, increase in MDA concentration and reduction in the concentration of protein, mucus, catalase and superoxide dismutase (P < 0.001). Pre-treatment with folic acid prevented the formation of ulcers by 32%, and attenuated the inhibition of mucus by 14%, CAT, 51% and SOD, 150%. Ranitidine afforded 56% prevention in ulcer formation with 67%, 55% and 78% attenuation of the inhibition of mucus, CAT and SOD, respectively, by indomethacin. While indomethacin-induced lipid peroxidation was attenuated by 58% reduction in MDA concentration on pretreatment with folic acid, Ranitidine offered 65% reduction. Basal and stimulated acid secretions were significantly reduced in the treated when compared with control animals. Folic acid produced a 21% reduction in the basal acid output when compared with the control animals (P < 0.05), and 140% reduction in histamine-induced acid response.

Conclusion:

The results indicate the gastroprotective activity of folic acid due its antioxidative and anti-secretory properties.     

叶酸代谢基因多态性的研究进展

育龄女性体内高同型半胱氨酸水平可导致不良孕产史,其代谢需要L-5-甲基四氢叶酸(即活性叶酸)参与。外源性增补的人工合成叶酸为活性叶酸的前体,在体内代谢后方可参与上述过程。叶酸代谢基因的多态性影响叶酸代谢过程,故通过检测特定基因位点的基因型,判断育龄女性叶酸代谢能力,从而个体化增补叶酸。现对近两年的相关文献进行综述,为临床开展精准医学及精准药学提供依据。     

Effect of ethanol on the metabolism of lithocholic acid in rat liver

Summary Lithocholic acid 24-C¹⁴ is converted by 20000x g-supernatant of rat liver homogenate into several products of higher polarity. 3-6-dihydroxy-5-cholanic acid is the main metabolite, whereas 7-hydroxylation occurs only to a small extent. Besides of the hydroxylations conjugation with taurine and the formation of a 3-sulfate ester of lithocholic acid can be demonstrated. Addition of ethanol to the enzymatic system results in an inhibition of the formation of 3,6-dihydroxy-5-cholanic acid, whereas no effect can be observed with respect to the formation of the other products. This inhibition is present also in 20000x g-supernatant obtained from rats pretreated with ethanol 100 min before being preparation from ethanol-pretreated rats amounts to 68% of the controls. The chrome P-450 mediated oxidative mechanism, which has been shown to be involved in microsomal 6-hydroxylation of bile acids.This work was supported by the Deutsche Forschungsgemeinschaft.     

Effect of phenobarbitone on the pharmacokinetics and tissue levels of amiodarone in the rat

Phenobarbitone pretreatment has been shown to increase amiodarone total clearance and decrease amiodarone elimination half-life after a single intravenous amiodarone dose in the rat. Coadministration of phenobarbitone with amiodarone for 7 days resulted in decreased tissue amiodarone levels compared to controls. These results may have implications for patients undergoing therapy with amiodarone and concomitant potent enzyme inducing drugs.     

Effect of folic acid deficiency on the synthesis of pteroylpolyglutamates

In order to evaluate the effect of folate deficiency on pteroylpolyglutamate synthesis in rat liver, the hepatic and urinary content of reduced folates, the distribution of pteroylpolyglutamates and the incorporation of i.p. injected 3H folic acid in polyglutamates have been studied. In deficient rats the hepatic content of reduced folates and the urinary amounts of reduced metabolites are lower and do not increase after vitamin treatment. Longer chain pteroylpolyglutamates are severely depleted and their content is not significantly modified by folic acid treatment. The percentage of labelled folic acid incorporated into pteroylglutamates is markedly decreased. The inability of deficient rat liver to synthesize polyglutamates might be ascribed to the decrease of pteroylpolyglutamate synthetase activity, and/or to the lower availability of tetrahydrofolates, the preferred substrates for the enzyme.     

Effect of riboflavin on the photolysis of folic acid in aqueous solution

A study of the photolysis of folic acid in aqueous solution by visible radiation in the presence of riboflavin has been made. The second-order rate constants for the bimolecular interaction of folic acid and riboflavin have been determined in the pH range 4.0-9.0. The rate pH profile shows a gradual increase in the rate up to pH 6.2 (pHmax) followed by a decrease up to pH 9.0, depending upon the susceptibility of ionic species involved in the interaction. The rate of photolysis varies from 0.50 x 10(3) M(-1) min(-1) (pH 9.0) and 0.63 x 10(3) M(-1) min(-1) (pH 4.0) to 3.0 x 10(3) M(-1) min(-1) (pH 6.2) in the pH range studied. A HPLC method has been used for the assay of folic acid and its photoproducts, pterine-6-carboxylic acid and p-aminobenzoyl-L-glutamic acid in the presence of riboflavin.     

Effect of folic acid on bone metabolism: a randomized double blind clinical trial in postmenopausal osteoporotic women

Background

In spite of several studies, the impact of homocysteine level and folic acid supplementation on bone metabolism is yet to be recognized. In this registered clinical trial (IRCT2014042217385N1), we aimed to find out the power of 6-month folic acid supplementation on homocysteine level and bone metabolism.

Methods

Forty postmenopausal osteoporotic women (50 to 87 years) were enrolled in the study. All participants were randomized to receive folic acid 1 mg (n = 17) or placebo (n = 14). At baseline, 3 months, and finally 6 months post intervention, the level of homocysteine, vitamin B12, and bone biomarkers were measured.

Results

Both groups were similar at baseline. The homocysteine decreased in both groups but statistically non-significant (P > 0.05). The changes of the serum level of vitamin B12, osteocalcin, and β cross laps were significant between groups after 6 months (P ≤ 0.05).

Conclusion

The trend of changes of bone biomarkers after 6 months folic acid supplementation shows that homocysteine concentration and/or folic acid supplementation have impact on the rate of bone metabolism. However, further investigations by larger sample size and differentiating age and gender are still needed to clarify the exact role of folate, homocysteine and vitamin B12.