Enhancement of bismuth toxicity by l-cysteine.
Bismuth-induced encephalopathies observed in France about twenty years ago have never received convincing explanation. In previous papers we have shown in animal experiments that L-cysteine enhanced Bi absorption without leading to encephalopathies. in this paper we have studied in greater detail the toxicity and the pharmacokinetics of Bi, and L-cysteine, given by intraperitoneal route to mice, singly and simultaneously as a Bi-L-cysteine complex. Bismuth and L-cysteine, were nontoxic singly since their LD50 were higher than 15 mmol/kg, but were toxic (LD50 = 0.3 mmol/kg) when they were given as a complex. The complex was about 50 times more toxic than the separate products. The changes in the levels of Bi and L-cysteine in blood versus time after the injection of the Bi-L-cysteine complex suggests that the complex entered into the blood under a non-dissociated form but just afterwards the complex dissociated and the levels of Bi decreased rapidly whereas the levels of L-cysteine remained high. The concentrations of Bi in tissues, blood, brain, kidney and liver were higher when it was given as the Bi-L-cysteine complex than alone. But the increase of the levels of Bi in tissues induced by L-cysteine was not sufficient to explain the 50 fold increase of the toxicity of the complex in comparison with Bi and L-cysteine given alone. Since the increase of the levels of Bi induced by L-cysteine was not sufficient to explain the increase of the toxicity of the complex, another explanation is required. We suggest that this increase results from the stimulation of peroxidation by bismuth and L-cysteine, as already observed for iron and L-cysteine. Other experiments are needed to verify the validity of this hypothesis.
Krari
N
N
Laboratoire de Pharmacologie, Centre Hospialier Universitaire, Angers Cedex, France
Mauras
Y
Y
Allain
D000818:Animals; D001729:Bismuth / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D001812:Blood-Brain Barrier / Q000187:drug effects; D003545:Cysteine / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D004338:Drug Combinations; D004357:Drug Synergism; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D014018:Tissue Distribution
D004338:Drug Combinations; D003545:Cysteine; D001729:Bismuth