Endogenous thiols enhance thallium toxicity

Abstract

Either L-methionine (L-met) or L-cysteine (L-cys), given alone and in combination with Prussian blue (PB) was characterized as treatment against acute thallium (Tl) toxicity in rats. Animals were intoxicated with 32 mg/kg Tl acetate corresponding to rat LD(50). Antidotal treatments were administered during 4 days, as follows: (1) vehicle, (2) L-met 100 mg/kg i.p. twice a day, (3) L-cys 100 mg/kg i.p. twice a day, (4) PB 50 mg/kg oral, twice a day, (5) L-met + PB and (6) L-cys + PB. Mortality was as follows: control 50%; L-met 80%; L-cys 80%; PB 20%; L-met + PB 90% and L-cys + PB 100%. In a different experiment, using 16 mg/kg of Tl, tissue levels of this metal were analyzed. PB treatment statistically diminished Tl content in body organs and brain regions (P<0.01). Whereas, separate treatments of L-met and L-cys failed to decrease Tl content in organs and brain regions; while its administration in combination with PB (L-met + PB and L-cys + PB groups) lowered Tl levels in body organs in the same extent as PB group. Results indicate that L-met and L-cys administered alone or in combination with PB should not be considered suitable treatments against acute Tl toxic effects because this strategy failed to prevent mortality and Tl accumulation in brain.

A comparison of hepatocyte cytotoxic mechanisms for thallium (I) and thallium (III)

“…In addition, it has been also reported that the endogenous amino acids with sulfhydryl groups ( L ‐methionine or L ‐cysteine) were not effective against thallous (Tl + ) acute toxicity when administered either alone or in combination with Prussian blue in rats. These compounds further enhanced thallous (Tl + ) toxicity (Montes et al, 2007).…”

Uncommon Heavy Metals, Metalloids and Their Plant Toxicity: A Review

“…The toxicity of thallium is probably based on its interactions with potassium, especially on its substitution in enzymatic systems such as (Na + /K+)-ATPase and other monovalent cation-activated enzymes, as well as a high affinity for sulfhydril groups of proteins and other biomolecules (Aoyama, 1989;Aoyama et al, 1988;Douglas et al, 1990). One work using mammalian cells as a biological model based on Tl interaction with sulhydrils groups of aminoacids L-cysteine and L-methionine demonstrated the enhancement of Tl toxicity in the presence of these aminoacids (so very important), but an unanswered question is what roles do plant thiol compounds play in the processes of thallium detoxication (Montes et al, 2007)?…”

Metallothionein alone or in combination with Prussian blue attenuates acute thallium systemic toxicity in rats.

“…MT reduced the thallium levels in tissues of metabolic importance, such as lung and liver, and also in the two brain regions containing the highest concentrations of thallium, such as hypothalamus and cerebellum. The systemic effect of MT did not produce an undesirable redistribution of Tl to the central nervous system (target organ of thallotoxicosis), as it has been observed after the administration of other chelating agents, such as D-penicillamine or endogenous thiols such as L-cysteine [35,36],…”

“…In order to get a new therapy against Tl poisoning and to increase the e cacy of PB, other chelating agents have been administered alone or in combination with PB, such as; sodium diethyldithiocarbamate, dimercaprol (British Anti-Lewisite), D-penicillamine and the thiol amino acid L-cysteine, as antidotes. However, rat studies have shown that when those chelating agents are administered alone, they cause removal of the metal from the deposit tissues, such as bone, muscle and others, redistributing it to the brain, which aggravates the symptomatology of the intoxication [34][35][36]. On the other hand, the administration of an endogenous metalloprotein, such as metallothionein I (MT-I), has shown a chelating and antioxidant effect (35%) on the liver of rats administrated with 32 mg/kg of thallium acetate [30].…”