Thiamine Whole Blood and Urinary Pharmacokinetics in Rats: Urethan-Induced Dose-Dependent Pharmacokinetics

Pipkin, J.D.; Stella, Valentino J.

doi:10.1002/jps.2600710208

Cited by 16 publications

(5 citation statements)

References 16 publications

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“…Possible causes for this over‐prediction could be that there was an appreciable delay between liver excision and termination of subsequent biotransformations, which the researchers achieved by homogenisation in Krebs‐Ringer solution 28. Alternatively the animals were used under urethane anaesthesia, which may have altered the pharmacokinetic behaviour of pentazocine, a phenomenon that has been reported for thiamine by Pipkin and Stella 50…”

Section: Discussionmentioning

confidence: 99%

Physiologically Based Pharmacokinetic Modeling 1: Predicting the Tissue Distribution of Moderate-to-Strong Bases

Rodgers

Leahy²,

Rowland

2005

Journal of Pharmaceutical Sciences

690

764

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Section: Discussionmentioning

confidence: 99%

Physiologically Based Pharmacokinetic Modeling 1: Predicting the Tissue Distribution of Moderate-to-Strong Bases

Rodgers

Leahy²,

Rowland

2005

Journal of Pharmaceutical Sciences

690

764

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“…A major part (about 70%) of both vitamins is known to be excreted from the body 24 h after the injection [ 74 , 75 ]. However, the injections significantly increase the internal pool of vitamins [ 76 ] stored in the liver, where concentrations of thiamine diphosphate and B6 vitamers are higher than in other tissues [ 14 , 77 ].…”

Section: Methodsmentioning

confidence: 99%

Physiological and Biochemical Markers of the Sex-Specific Sensitivity to Epileptogenic Factors, Delayed Consequences of Seizures and Their Response to Vitamins B1 and B6 in a Rat Model

et al. 2021

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The disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause seizures. Our study aims at revealing therapeutic potential of vitamins B1 and B6 by estimating the short- and long-term effects of their combined administration with the seizure inductor pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to modified Racine’s scale, along with delayed physiological and biochemical consequences the next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than the male rats. The next day after a seizure, sex differences in behavior and brain biochemistry arise. The induced sex differences in anxiety and locomotor activity correspond to the disappearance of sex differences in the brain aspartate and alanine, with appearance of those in glutamate and glutamine. PTZ decreases the brain malate dehydrogenase activity and urea in the males and the phenylalanine in the females. The administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5–2 h) between the administration of the vitamins and PTZ. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. The delayed effects of vitamins and/or PTZ are mostly sex-specific and interacting. Our findings on the sex differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications.

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“…Taking into account that the excretion of exogenous thiamine in rats occurs in app. 48 hr (Pipkin & Stella, 1982), whereas daily administration of the doses of thiamine up to 200 mg/kg increased the brain thiamine levels and/or total thiamine pool in rodents killed 24 hr after the administration (Bettendorff, Weekers, Wins, & Schoffeniels, 1990;Vignisse et al, 2017), our protocol, where rats were killed 24 hr after administration of 400 mg/kg thiamine, should allow one to observe not only the systemic action of thiamine compounds, but also the effects of the elevated thiamine pool in the brain.…”

Section: Rats Were Purchased From the State Research Center Of Russianmentioning

confidence: 99%

Diurnal regulation of the function of the rat brain glutamate dehydrogenase by acetylation and its dependence on thiamine administration

Aleshin

Mkrtchyan

Kaehne

et al. 2020

Journal of Neurochemistry

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Glutamate dehydrogenase (GDH) is essential for the brain function and highly regulated, according to its role in metabolism of the major excitatory neurotransmitter glutamate. Here we show a diurnal pattern of the GDH acetylation in rat brain, associated with specific regulation of GDH function. Mornings the acetylation levels of K84 (near the ADP site), K187 (near the active site), and K503 (GTP‐binding) are highly correlated. Evenings the acetylation levels of K187 and K503 decrease, and the correlations disappear. These daily variations in the acetylation adjust the GDH responses to the enzyme regulators. The adjustment is changed when the acetylation of K187 and K503 shows no diurnal variations, as in the rats after a high dose of thiamine. The regulation of GDH function by acetylation is confirmed in a model system, where incubation of the rat brain GDH with acetyl‐CoA changes the enzyme responses to GTP and ADP, decreasing the activity at subsaturating concentrations of substrates. Thus, the GDH acetylation may support cerebral homeostasis, stabilizing the enzyme function during diurnal oscillations of the brain metabolome. Daytime and thiamine interact upon the (de)acetylation of GDH in vitro. Evenings the acetylation of GDH from control animals increases both IC50GTP and EC50ADP. Mornings the acetylation of GDH from thiamine‐treated animals increases the enzyme IC50GTP. Molecular mechanisms of the GDH regulation by acetylation of specific residues are proposed. For the first time, diurnal and thiamine‐dependent changes in the allosteric regulation of the brain GDH due to the enzyme acetylation are shown.

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Thiamine Whole Blood and Urinary Pharmacokinetics in Rats: Urethan-Induced Dose-Dependent Pharmacokinetics

Cited by 16 publications

References 16 publications

Physiologically Based Pharmacokinetic Modeling 1: Predicting the Tissue Distribution of Moderate-to-Strong Bases

Physiologically Based Pharmacokinetic Modeling 1: Predicting the Tissue Distribution of Moderate-to-Strong Bases

Physiological and Biochemical Markers of the Sex-Specific Sensitivity to Epileptogenic Factors, Delayed Consequences of Seizures and Their Response to Vitamins B1 and B6 in a Rat Model

Diurnal regulation of the function of the rat brain glutamate dehydrogenase by acetylation and its dependence on thiamine administration

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