scholarly journals Effects of oestradiol and vitamin B6 on tryptophan metabolism in the rat: implications for the interpretation of the tryptophan load test for vitamin B6 nutritional status

1983 ◽  
Vol 50 (1) ◽  
pp. 33-42 ◽  
Author(s):  
David A. Bender
Keyword(s):  
Body Weight ◽  
Vitamin B6 ◽  
Load Test ◽  
Tryptophan Metabolism ◽  
Vitamin B ◽  
High Dose ◽  
Positional Isomers ◽  
Drug Induced ◽  
Tryptophan Oxygenase

1. The effects of the administration of oestradiol and vitamin B6 on tryptophan metabolism in the rat have been assessed by measurement of the release of 14CO2 from [14C]tryptophan, in vivo, in order to determine whether, and to what extent, the abnormalities of tryptophan metabolism that are associated with oestrogen administration can be attributed to drug-induced vitamin B6 deficiency or depletion. Two positional isomers of [14C]tryptophan have been used; [ring-2-14C]tryptophan as an index of the activity of tryptophan oxygenase (L-tryptophan: oxygen oxidoreductase (decyclizing), EC 1.13.11.11) and [methylene-14C]trytophan as an index of the activity of kynureninase (L-kynurenine hydrolase, EC 3.7.1.3).2. The administration of 500 μg oestradiol/kg body-weight led to a reduction in the release of 14CO2 from both positional isomers of tryptophan, suggesting that the activities of both tryptophan oxygenase and kynureninase are reduced following oestrogen treatment. The kinetics of the release of 14CO2 from [methylene-14C]tryptophan after the administration of oestradiol were compatible with competitive inhibition of kynureninase by oestradiol or a metabolite.3. The administration of 10 mg pyridoxine hydrochloride/kg body-weight also reduced the production of 14CO2 from both positional isomers of 14C]tryptophan, suggesting some toxicity of such a high dose of the vitamin.4. In animals which had received the supplementary dose of vitamin B6, the administration of oestradiol led to further reduction in the production of 14CO2 from [ring-2-14C]tryptophan, suggesting a further reduction in the activity of tryptophan oxygenase, and an increase in the production of 14CO2 from [methylen-14C]tryptophan, but with a delay in the peak of production.5. These results confirm that there is no induction of tryptophan oxygenase by oestradiol, but rather reduced activity of the enzyme after the administration of a relatively high dose of the hormone. They also confirm that the inhibition of kynureninase by oestrogen metabolites that has been reported previously in partially-purified enzyme preparations also occurs in vivo.6. It is suggested that the abnormal results of the tryptophan load test that have been reported in women receiving oestrogens, and which have been interpreted as indicating some extent of drug-induced vitamin B6 deficiency, can be accounted for by the inhibition of tryptophan metabolism by oestrogens or their metabolites. Therefore it seems likely that the practice of administering supplements of vitamin B6 to women receiving oestrogens may not be appropriate, and indeed may exacerbate the changes in tryptophan metabolism that result from the administration of oestrogens. The tryptophan load test would appear to be unreliable as an index of vitamin B6 nutritional status in women receiving oestrogens.

scholarly journals Tryptophan metabolism in vitamin B6-deficient mice

1990 ◽  
Vol 63 (1) ◽  
pp. 27-36 ◽  
Author(s):  
David A. Bender ◽  
Eliud N. M. Njagi ◽  
Paul S. Danielian
Keyword(s):  
Urinary Excretion ◽  
Intraperitoneal Injection ◽  
Vitamin B6 ◽  
Isolated Hepatocytes ◽  
Tryptophan Metabolism ◽  
Xanthurenic Acid ◽  
Vitamin B ◽  
Tryptophan Metabolites ◽  
Deficient Mice

Vitamin B6 deficiency was induced in mice by maintenance for 4 weeks on a vitamin B6-free diet. Tryptophan metabolism was assessed by determining the urinary excretion of tryptophan metabolites, the metabolism of [14C]tryptophan in vivo and the formation of tryptophan and niacin metabolites by isolated hepatocytes. The vitamin B6-deficient animals excreted more xanthurenic acid and 3-hydroxykynurenine, and less of the niacin metabolites N1-methyl nicotinamide and methyl-2-pyridone-4-carboxamide, than did control animals maintained on the same diet supplemented with 5 mg vitamin B6/kg. After intraperitoneal injection of [14C]tryptophan, vitamin B6-deficient mice showed lower liberation of14CO2 from [methylene-14C]tryptophan and [U-14C]tryptophan than did controls, indicating impairment of kynureninase (EC 3.7.1.3) activity. There was no difference between the two groups of animals in the metabolism of [ring-2-14C]tryptophan. Hepatocytes isolated from the vitamin B6-deficient animals formed more 3-hydroxykynurenine and xanthurenic acid than did cells from control animals, but also formed more NADP and free niacin.

Pyridoxine and GABA as antagonists to drug-induced convulsions in monkeys

1965 ◽  
Vol 20 (6) ◽  
pp. 1337-1340 ◽  
Author(s):  
Lenore M. Kopeloff ◽  
Joseph G. Chusid
Keyword(s):  
Macaca Mulatta ◽  
Vitamin B6 ◽  
Aminobutyric Acid ◽  
Experimental Epilepsy ◽  
Protective Effects ◽  
Gamma Aminobutyric Acid ◽  
Drug Induced

The antagonistic properties of pyridoxine and gamma aminobutyric acid (GABA) toward convulsant drugs were evaluated by determining their in vivo protective effects when administered parenterally prior to challenge. In a group of 28 monkeys composed of 19 chronic epileptics and 9 controls, pyridoxine and GABA provided variable grades of protection against the convulsant actions of methoxypyridoxine, semicarbazide, and to a lesser degree, pentamethylenetetrazol (Metrazol) and 3,3-methylethylglutarimide (Megimide). Neither pyridoxine nor GABA protected epileptic, brain-operated nonepileptic, or normal monkeys from the convulsant actions of parenteral picrotoxin. No evidence therefore was found in these experiments to support the suggestion that GABA (or pyridoxine) and picrotoxin are antagonistic to each other. experimental epilepsy in Macaca mulatta; gamma aminobutyric acid and vitamin B6 as anticonvulsants Submitted on February 15, 1965

In vivo hepatotoxicity of chemically modified nanocellulose in rats

2019 ◽  
Vol 39 (2) ◽  
pp. 212-223 ◽  
Author(s):  
CA Otuechere ◽  
A Adewuyi ◽  
OL Adebayo ◽  
IA Ebigwei
Keyword(s):  
Body Weight ◽  
Relative Weight ◽  
High Dose ◽  
Hydroxyl Groups ◽  
Oral Toxicity ◽  
Tissue Samples ◽  
Liver Histopathology ◽  
Biological Functionality ◽  
Oxide Synthase

Chemical modification of cellulose is currently attracting attention as researchers attempt to take advantage of the abundance of hydroxyl groups on its surface to introduce extra biological functionality. However, the possible deleterious effect of exposure to functionalized nanocellulose (CSN) remains a concern. Therefore, this study aims to explore the potential mechanisms of hepatotoxicity of CSN modified with oxalate ester (NCD) in rats. A 7-day repeated oral toxicity study of NCD at the doses of 50 and 100 mg kg−1 body weight was conducted, and plasma and liver tissue samples were assayed using biochemical analysis, liver histopathology, and protein expression. NCD, at both doses, did not significantly ( p > 0.05) alter the relative weight of liver, alkaline phosphatase activity, and lipid peroxidation levels of the animals. However, NCD at the dose of 100 mg kg−1 body weight significantly elevated aspartate aminotransferase, alanine aminotransferase, and myeloperoxidase activities. NCD also enhanced the immunohistochemical expression of inducible nitric oxide synthase and Bcl-2-associated X protein in the liver of rats. Histological observations revealed necrosis and severe cellular infiltration at the high-dose treatment. Our study provides an experimental basis for the safe application of NCDs.

Schistosoma mansoni: structural damage and tegumental repair after in vivo treatment with praziquantel

Parasitology ◽  
1987 ◽  
Vol 94 (2) ◽  
pp. 243-254 ◽  
Author(s):  
M. K. Shaw ◽  
D. A. Erasmus
Keyword(s):  
Immune Response ◽  
Body Weight ◽  
Schistosoma Mansoni ◽  
Structural Damage ◽  
Post Treatment ◽  
Drug Induced ◽  
Male And Female ◽  
Extensive Damage

SUMMARYThe long-term, in vivo effects of a single, subcurative dose (200 mg/kg body weight of mouse) of praziquantel on the structure of adult Schistosoma mansoni and on the process and speed of tegumental repair are described. In both male and female worms praziquantel caused often extensive damage to the tegument, in the form of surface blebbings, swellings and lesions, and vacuolization and disruption of the subtegumental tissues. Repair of the drug-induced tegumental damage occurred slowly with partial and, more rarely, complete repair only being seen after 65 days post-treatment (p.t.), although signs of damage were still observed, particularly in male worms, at 100 days p.t. In contrast, repair of damage to the subtegumental/parenchymal tissues including the tegumental perikarya occurred relatively quickly, with the majority of worms examined appearing normal by 8–12 days p.t. The possible role(s) of the host immune response in relation to the speed of tegumental repair in vivo is discussed.

scholarly journals Kynurenine metabolism in vitamin-B-6-deficient rat liver after tryptophan injection

1984 ◽  
Vol 220 (3) ◽  
pp. 693-699 ◽  
Author(s):  
F Takeuchi ◽  
Y Shibata
Keyword(s):  
Rat Liver ◽  
Tryptophan Metabolism ◽  
Vitamin B ◽  
High Dose ◽  
Kynurenine Aminotransferase ◽  
A Value ◽  
Km Value ◽  
Kynurenine Metabolism ◽  
Total Enzyme

Tryptophan contents of liver, serum and kidney were determined in normal and vitamin-B-6-deficient rats after tryptophan injection. Tryptophan contents of normal and B-6-deficient liver were different, but not those in serum and kidney. Both kynurenine and 3-hydroxykynurenine accumulated in B-6-deficient liver more than in the normal. The 3-hydroxykynurenine contents after tryptophan injection (30 mg/100 g body wt.) increased to 1380 nmol/g of liver at 1-1.5 h, a value sufficient to produce xanthurenate, in view of the Km value of kynurenine aminotransferase. The enzymes metabolizing kynurenine were assayed at various times after tryptophan injection. The activity of kynureninase holoenzyme in B-6-deficient liver was much decreased, but the activity of total enzyme was not changed. It appeared that a high dose of tryptophan in B-6-deficient rats could cause a greater deficiency of pyridoxal 5-phosphate. Tryptophan metabolism in B-6-deficient rat liver after tryptophan administration is discussed.

scholarly journals Importance of penicillinase production for activity of penicillin alone or in combination with sulbactam in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

1996 ◽  
Vol 40 (5) ◽  
pp. 1219-1224 ◽  
Author(s):  
B Fantin ◽  
J Pierre ◽  
N Castéla-Papin ◽  
L Saint-Julien ◽  
H Drugeon ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Synergistic Effect ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Limiting Factor ◽  
High Dose ◽  
Methicillin Resistant

The activity of penicillin, alone and in combination with sulbactam, against a heterogeneously methicillin-resistant, penicillinase-producing clinical isolate of Staphylococcus aureus and its penicillinase-negative derivative was investigated in vitro and in a rabbit experimental endocarditis model. Penicillin was significantly more effective than vancomycin against the penicillinase-negative derivative in vivo (P < 0.001), and it sterilized 25% of the vegetations. The combination of penicillin and sulbactam exhibited an in vivo synergistic effect on the penicillinase-producing strain (P < 0.01) but did not produce any advantage over treatment with vancomycin, even when a high dose of sulbactam was used (100 mg/kg of body weight every 6 h). This combination was significantly less effective against the penicillinase-producing strain than was penicillin alone against the penicillinase-negative derivative (P < 0.03). In addition, the most resistant subpopulation of the surviving bacteria, which grew on agar containing 16 micrograms of methicillin per ml, was detected in 5 of 6 animals treated with penicillin and a high dose of sulbactam against the penicillinase-producing strain compared with only 1 of 12 animals treated with penicillin alone against the penicillinase-negative derivative (P < 0.01). We conclude that penicillin is highly effective against penicillinase-negative methicillin-resistant S. aureus and that penicillinase production, rather than methicillin resistance, appears to be the limiting factor for the activity of the penicillin-sulbactam combination against penicillinase-producing, methicillin-resistant S. aureus.

scholarly journals Vitamin B6: Beyond Adequacy

2011 ◽  
Vol 16 (1) ◽  
pp. 29-39 ◽  
Author(s):  
David A. Bender
Keyword(s):  
Vitamin B6 ◽  
Sensory Nerve ◽  
Vitamin B ◽  
High Dose ◽  
Antihypertensive Action ◽  
Tunnel Syndrome ◽  
Plausible Mechanism ◽  
Intervention Trials ◽  
Antidepressant Action ◽  
Good Agreement

There is good agreement concerning average requirements and reference intakes for vitamin B6but less agreement over safe upper levels from supplements. High-dose supplements cause sensory nerve damage. Supplements of vitamin B6have been advocated for treatment of the premenstrual syndrome, with little evidence of efficacy. There are plausible mechanisms for an antidepressant action and protection against steroid hormone—dependent cancers but no evidence from clinical trials. Pyridoxamine reduces the glycation of proteins and so could be beneficial in preventing the adverse effects of poor glycemic control in diabetes. There are plausible mechanisms for an antihypertensive action but only suggestive evidence from small intervention trials. There is no evidence that supplements of vitamin B6have any beneficial effect in hyperhomocysteinemia. There is neither a plausible mechanism nor any evidence from controlled trials for any effect of supplements of vitamin B6in preventing a decline in cognitive function with aging, amelioration of dementia or autism, or improvement of the carpal tunnel syndrome.

PENICILLAMINE AND VITAMIN B6 INTERRELATIONSHIPS IN THE RAT

1963 ◽  
Vol 41 (5) ◽  
pp. 1215-1222 ◽  
Author(s):  
J. G. Heddle ◽  
E. W. McHenry ◽  
G. H. Beaton
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Vitamin B6 ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Vitamin B ◽  
Transaminase Activity ◽  
Pyridoxine Hydrochloride ◽  
Antagonistic Effects

DL-Penicillamine administered in the diet at the 0.25% level produced a marked lowering of food intake and body weight. Using blood transaminase activities as criteria, a definite antagonism to vitamin B6 was demonstrated. The response of animals to the drug did not differ between sexes. Transaminase activity changes were apparent within 13 days of treatment. They were not the result of a reduced food intake. Administration of 800 μg of pyridoxine hydrochloride per 10 g of diet to animals receiving penicillamine approximated the maximal prevention of the effects of the drug upon food intake, body weight, and transaminase activity. The effects were not completely prevented by dosages of vitamin B6 as high as 2000 μg per 10 g of diet. Attention is drawn to the possible significance of these studies in the treatment of patients (Wilson's disease) with penicillamine. On the basis of extrapolations from the present studies in rats, 50 mg of pyridoxine hydrochloride might be expected to give near-maximal protection against possible vitamin B6-antagonistic effects of 1.5 g of DL-penicillamine.

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