Thiamine hydrochloride

Biological Activity

In vitro: Thiamine (50 mM), in addition to its nutritional value, induces systemic acquired resistance (SAR) in rice, tobacco, cucumber, and Arabidopsis. Thiamine-treated rice, Arabidopsis (Arabidopsis thaliana), and vegetable crop plants shows resistance to fungal, bacterial, and viral infections. Thiamine treatment induces the transient expression of pathogenesis-related (PR) genes in rice and other plants. In addition, Thiamine treatment potentiates stronger and more rapid PR gene expression and the up-regulation of protein kinase C activity. Vitamin B1 (10 μM) prevents acetaldehyde-induced inhibition of myocyte shortening in adult rat ventricular myocytes. Vitamin B1 (10 μM) effectively blunts the acetaldehyde-induced depression in ±dL/dt in adult rat ventricular myocytes. Vitamin B1 (10 μM) prevents acetaldehyde-induced shortening of time-to-peak shortening in adult rat ventricular myocytes. Vitamin B1 (10 μM) prevents acetaldehyde-induced elevation in both protein carbonyl formation and caspase-3 activation in adult rat ventricular myocytes. Thiamine uptake is energy- and temperature-dependent, pH-sensitive, Na+-independent, saturable at both the nanomolar (apparent Km, 30 nM) and the micromolar (apparent Km, 1.72 mM) concentration ranges in ARPE-19 cells. Uptake of Thiamine is adaptively regulated by extracellular substrate level via transcriptionally mediated mechanisms that involve both hTHTR-1 and hTHTR-2 in ARPE-19 cells, it is also regulated by an intracellular Ca2+-calmodulin-mediated pathway. Thiamine-responsive megaloblastic anemia (TRMA) fibroblasts are rescued from death with 10 nM-30 nM Thiamine (in the range of normal plasma thiamine concentrations). Normal fibroblasts exhibits saturable, high-affinity thiamine uptake (Km 400 nM-550 nM; Vmax 11 pmol/min/1×106 cells), while TRMA fibroblasts lacks detectable high-affinity uptake. At 30 nM Thiamine, the rate of uptake of Thiamine by TRMA fibroblasts is 10-fold less than that of wild-type, which explains the increased apoptosis of TRMA fibroblasts.

In vivo: Thiamine deficiency results in amyloid precursor protein immunoreactivity accumulated in swollen neurites within, or around lesions in rats, or in abnormal clusters in mice.

Protocol (for reference only)

Cell Experiment
Cell lines	HL-60 cells
Preparation method	HL-60 cells were pre-treated with 0.25 μg/ml of either cycloheximide or tetrathylammonium, a big potassium channel (BK) blocker, for 2 hours and then cultured for 12 hours with or without thiamine (100 μM) and stained with Giemsa.
Concentrations	100 μM
Incubation time	12 h

Animal Experiment
Animal models
Formulation
Dosages
Administration

Chemical Information

Molecular Weight	337.27
Formula	C12H17N4OS.HCl
CAS Number	67-03-8
Solubility (25°C)	68 mg/mL in water
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Dong W, et al. Plant Cell Physiol. Enhancement of Thiamin Content in Arabidopsis thaliana by Metabolic Engineering.

[2] Sugimori N, et al. PLoS One. Paraptosis Cell Death Induction by the Thiamine Analog Benfotiamine in Leukemia Cells