Lymphopenic effects on mice of a component of ammonia caramel, 2‐acetyl‐4(5)‐tetrahydroxybutylimidazole (THI)

Abstract

Summary A derivative of ammonia caramel colour (AC) is known to induce a selective lymphopenia in rats. Accordingly, the haematological effects were studied in mice of oral administration in drinking water of 2-acetyl-4(5)-tetrahydroxybutylimidazole (THI), the component of AC responsible for lymphopenia. Initially five groups of BALB/c mice (five mice per group) were given doses of THI ranging from 0 to 200 parts/10^ and bled weekly. Doses of THI from 5 to 100 parts/10^ had no effect on circulating leucocytes over 6 weeks, but lymphopenia occurred with 200 parts/10^. An increase in the concentration of T"HI to 400 parts/10^ in the group on the lowest dose resulted in lymphopenia. An increase indosagein two groups of mice, to 1000 and 2000 parts/10^. resulted in marked lymphopenia. The number of neutrophils. eosinophils and monocytes remained unchanged throughout the experiment. Measurement of the proportions of CD4(L3T4)"'" and CD8(Ly2)"^ lymphocytes in lymph nodes from mice on high doses of THI did not show a selective depression of either subset, although both were increased relative to non-T cells. THI causes a selective lymphopenia in mice, as in rats, but at relatively higher doses, and merits investigation in mice as an experimental treatment for states of lymphocyte excess or overactivity.

Suppressive Effect of 2-Acetyl-4-Tetrahydroxybutylimidazole on Contact Hypersensitivity in the Skh: HR Hairless Mouse

“…However, an earlier study [9] of the effects of THI on mice has shown that BALB/c mice were made lymphopénie following prolonged dosing at the lowest concentration of 200 mg/l THI administered in the drinking water, with marked lymphopenia at higher concentrations of 1,000 and 2,000 mg/l. In rats, however, 10 104 Reeve/Boehm-Wilcox/Bosnic/Rozinova THI Suppresses Contact Hypersensitivity mg/1 THI resulted in detectable significant lymphopenia after 7 days (normal vitamin B(, nutrition), and in complete abrogation of the delayed-type hypersensitivity reaction in vitamin B,,-deficicnt rats.…”

“…The lymphopenic effect of THI appeared not to be sustained following excretion of the compound, and the antagonism of the THI lymphopenia with increas ing doses of pyridoxine suggested that pyridoxine and THI compete for the same binding site, perhaps on lympho cytes [6], Significant lymphopenia has been observed in rats 24 h after a single parenteral dose of 1 mg THI/kg body weight [6] and. in the drinking water, at doses as low as 1 mg/l (equivalent to 0.1 mg/kg body weight/day) after 7 days [7,8], In BALB/c mice, however, treatment with at least 200 mg/l for 6 weeks was necessary to observe lymphopenia [9], indicating a reduced susceptibility to THI compared with rats.…”

Sphingosine 1-phosphate lyase inhibition by 2-acetyl-4-(tetrahydroxybutyl)imidazole (THI) under conditions of vitamin B6 deficiency

“…A series of studies has shown that THI induces lymphopenia and affects the immune system in animals [1][2][3][4][5]. Although the mechanism was unknown for a long time, Schwab et al revealed that THI exhibits its biological effects through sphingosine 1-phosphate (S1P) lyase (SPL) inhibition [6].…”

Synthesis of thiazole analogues of the immunosuppressive agent (1R,2S,3R)-2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole

“…THI has been found to cause lymphopenia (depression of blood lymphocyte counts), without any apparent side-effects, in mice and rats that have been given THI in their drinking water. 8,9 Thus THI and its analogues have potential applications as an immunosuppressive agent in organ transplant biology or for preventing the onset of diabetes. 10 Our earlier studies showed that compound 2, the 5-thiazole analogue of THI, had essentially the same activity versus concentration profile as THI in causing lymphopenia in mice, while the pentahydroxylpentyl derivative 3 showed a slightly higher activity at the same concentration.…”

“…[8][9][10] THI is a minor component of the common food additive Caramel Colour III. THI has been found to cause lymphopenia (depression of blood lymphocyte counts), without any apparent side-effects, in mice and rats that have been given THI in their drinking water.…”