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

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.

1963 ◽  
Vol 41 (1) ◽  
pp. 1215-1222 ◽  
Author(s):  
J. G. Heddle ◽  
E. W. McHenry ◽  
G. H. Beaton

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.


1965 ◽  
Vol 43 (4) ◽  
pp. 591-599 ◽  
Author(s):  
M. C. Cheney ◽  
G. H. Beaton

Factorial design experiments in rats revealed that blood transaminase activity was sensitive to vitamin B6 dosage and was not affected by concurrent variation in riboflavin or thiamine administration.The blood transaminase activity was a better index of vitamin B6 nutritional status than was body weight response or liver transaminase activity. Similarly, erythrocyte transketolase activity was found to reflect thiamine dosage, and plasma riboflavin level to reflect riboflavin dosage, regardless of manipulation of pyridoxine dosage.


1983 ◽  
Vol 50 (1) ◽  
pp. 33-42 ◽  
Author(s):  
David A. Bender

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.


2015 ◽  
Vol 4 ◽  
Author(s):  
Marie-Édith Côté-Robitaille ◽  
Christiane L. Girard ◽  
Frédéric Guay ◽  
J. Jacques Matte

AbstractHomocysteine (Hcy) is an intermediary sulphur amino acid recognised for pro-oxidative properties in several species which may weaken immune competence in piglets. In this species, there is an acute 10-fold increase of concentrations of plasma Hcy (pHcy) during the first 2 weeks of life. The present experiment aimed to determine if pHcy in piglets can be regulated by oral supplementations of betaine as a methyl group supplier, creatine for reducing the demand for methyl groups, choline with both previous functions and vitamin B6 as enzymic co-factor for Hcy catabolism. A total of seventeen sows (second parity) were fed gestation and lactation diets supplemented with folic acid (10 mg/kg) and vitamin B12 (150 µg/kg). Eight piglets in each litter received daily one of the eight following oral treatments (mg/kg body weight): (1) control (saline); (2) betaine (50); (3) choline (70); (4) creatine (300); (5) pyridoxine (0·2); (6) treatments 2 and 5; (7) treatments 3 and 4; and (8) treatments 2, 3, 4 and 5. According to age, pHcy increased sharply from 2·48 µm at birth to 17·96 µm at 21 d of age (P < 0·01). Concentrations of pHcy tended to be lower (P = 0·09) in treated than in control piglets but the highest and sole pairwise significant decrease (23 %) was observed between treatments 1 and 8 (P = 0·03). Growth from birth to 21 d of age was not influenced by treatments (P > 0·70). Therefore, it appears possible to reduce pHcy concentrations in suckling piglets but a combination of all chosen nutrients is required.


2016 ◽  
Vol 18 (3(71)) ◽  
pp. 209-214
Author(s):  
O.V. Yaremko ◽  
R.A. Pelenio

The influence of pyridoxine hydrochloride (vitamin B6) activity in serum aminotransferases in dairy calves growing period (1 to 90 days). Calves control group received basic diet, but research from the first days of life to the basic diet added pyridoxine hydrochloride doses: I group – 1.0; II – 2.0; III – 3.0; IV – 4.0 V and group – 5.0 mg / kg body weight. Blood for the study was before the morning feeding at 1, 5, 21, 60 and 90 days after birth. Research aminotransferase activity was determined by the content of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the ratio between them using factor where Ritisa.It was established that the addition of colostrum to milk and pyridoxine hydrochloride leads to increased aminotransferase activity. The low activity of AST and ALT in blood serum of calves of all groups was on the first day of life. Effects of pyridoxine hydrochloride on aminotransferase activity was shown during the research period. Adding to the colostrum vitamin B6 increases the activity of AST by 10 percent or more doses of only 3.0, 4.0 and 5.0 mg/kg body weight. Probably higher AST activity detected in animals II, III, IV and V groups at 21 and 60 days. On the 90th day of the experiment AST activity in serum of calves research groups stabilized, which may indicate the ability of vitamin B6 stimulate the growth and development of microorganisms scar. Adding to the colostrum and milk pyridoxine hydrochloride led to growth within the physiological norm ALT activity. Significant difference between ALT control and experimental groups established in calves III, IV and V groups 21, 60 and 90 day experiment, calves and the second group on day 90 of the experiment. Stabilization of enzyme activity investigated is set to 21 days in calves group IV, 60 – the third group and 90 days in calves second group. The ratio of AST to ALT (coefficient de Ritis) do not go beyond the physiological norm. For correction of vitamin–supply calves 1–21 days old is the optimal dose of daily supplement intake of calves 4 mg / kg body weight of vitamin B6 for calves with 21–60–day age – 3 mg / kg and 60 calves 90–day age – 2 mg / kg body weight. 


2020 ◽  
Vol 117 (4) ◽  
pp. 2076-2083 ◽  
Author(s):  
Clavia Ruth Wooton-Kee ◽  
Matthew Robertson ◽  
Ying Zhou ◽  
Bingning Dong ◽  
Zhen Sun ◽  
...  

Inactivating mutations in the copper transporter Atp7b result in Wilson’s disease. The Atp7b−/− mouse develops hallmarks of Wilson’s disease. The activity of several nuclear receptors decreased in Atp7b−/− mice, and nuclear receptors are critical for maintaining metabolic homeostasis. Therefore, we anticipated that Atp7b−/− mice would exhibit altered progression of diet-induced obesity, fatty liver, and insulin resistance. Following 10 wk on a chow or Western-type diet (40% kcal fat), parameters of glucose and lipid homeostasis were measured. Hepatic metabolites were measured by liquid chromatography–mass spectrometry and correlated with transcriptomic data. Atp7b−/− mice fed a chow diet presented with blunted body-weight gain over time, had lower fat mass, and were more glucose tolerant than wild type (WT) littermate controls. On the Western diet, Atp7b−/− mice exhibited reduced body weight, adiposity, and hepatic steatosis compared with WT controls. Atp7b−/− mice fed either diet were more insulin sensitive than WT controls; however, fasted Atp7b−/− mice exhibited hypoglycemia after administration of insulin due to an impaired glucose counterregulatory response, as evidenced by reduced hepatic glucose production. Coupling gene expression with metabolomic analyses, we observed striking changes in hepatic metabolic profiles in Atp7b−/− mice, including increases in glycolytic intermediates and components of the tricarboxylic acid cycle. In addition, the active phosphorylated form of AMP kinase was significantly increased in Atp7b−/− mice relative to WT controls. Alterations in hepatic metabolic profiles and nuclear receptor signaling were associated with improved glucose tolerance and insulin sensitivity as well as with impaired fasting glucose production in Atp7b−/− mice.


1956 ◽  
Vol 184 (2) ◽  
pp. 309-311
Author(s):  
Chung Suk Song ◽  
William N. Pearson ◽  
William J. Darby

Adult female albino Sprague-Dawley rats subjected to 500 r (backscatter) of whole-body x-irradiation exhibit an increase in the urinary excretion of the B6 group of vitamins beginning on the 2nd day after irradiation. However, control animals, whose food intake was limited to that of the irradiated group, excreted amounts of vitamin B6 that were quantitatively similar. It is concluded that the increase of vitamin B6 excretion found after x-irradiation is a reflection of the irradiation-induced anorexia and is not due to tissue changes brought about by irradiation per se.


1969 ◽  
Vol 23 (3) ◽  
pp. 705-707
Author(s):  
M. C. Nath ◽  
N. V. Shastri

1. Experiments were undertaken to study the effect of daily intraperitoneal injection of acetoacetate for 90 days on vitamin B6 status in male albino rats. The initial dose of acetoacetate was 50 mg per kg body-weight, which was increased by 50 mg per kg body-weight every 15 days.2. Urinary excretion of vitamin B6 was found to decrease after 30 days in acetoacetatetreated rats. After 75 days urinary values of vitamin B6 were considerably lower in such rats than in the corresponding control rats.3. When acetoacetate injections were stopped after 90 days and the rats were fed L-tryptophan (100mg per rat), they were found to excrete significantly greater amounts of urinary kynurenine, hydroxykynurenine and xanthurenic acid than the corresponding controls.4. Blood and liver vitamin Be levels were found to be lower in rats treated with acetoacetate for 90 days than in the untreated rats.


1965 ◽  
Vol 43 (4) ◽  
pp. 579-589 ◽  
Author(s):  
M. C. Cheney ◽  
D. M. Curry ◽  
G. H. Beaton

The lowering of blood glutamic–oxaloacetic (GOT) and glutamic–pyruvic (GPT) transaminase activities was found to be specific for vitamin B6 deprivation among several B vitamins tested and in the presence of a simultaneous restriction of eight B vitamins, cortisone administration, or variation of dietary protein level. It was found that changes in blood transaminase activity did not always parallel those seen in liver transaminase activity. In the determination of vitamin B6 nutritional status, blood GPT activity appeared to be more sensitive than GOT activity and would seem to be as sensitive an indicator as xanthurenic acid excretion after a tryptophan load.


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