Size exclusion chromatography provides evidence for a possible role of L-histidine in the organ availability of the carcinogen Ni2+

The emission of toxic metals into the global environment poses threats to ecosystems and human health that are incompletely understood. Since Ni is widely used for the manufacturing of alloys used in the high-tech industry, certain human populations are exposed to this carcinogenic and neurotoxic metal near mines and manufacturing sites. After Ni 2+ is absorbed from the gastrointestinal tract into the bloodstream, it is distributed to target organs by poorly understood bioinorganic processes which ultimately define its exposure-response relationship. To gain insight, we have employed size exclusion chromatography (SEC) using a 25 mM Tris buffer (pH 7.4) mobile phase hyphenated to a flame atomic absorption spectrometer (FAAS) as the Ni-specific detector. The chromatography of a Ni-human serum albumin (HSA) complex on this SEC-FAAS system revealed the elution of the intact complex. To delineate the role of small molecular weight ligands in plasma in the translocation of Ni 2+ from its HSA binding sites to target organs, we then chromatographed the HSA-Ni complex with mobile phases containing 2.0 mM L-cysteine, L-glutathione, N -acetyl-L-cysteine, DL-homocysteine, L-methionine, L-histidine (His) or taurine. Since His most effectively mobilized Ni 2+ from HSA, we also chromatographed the HSA-Ni complex with 1.5, 1.0 and 0.5 mM His mobile phases and observed a mobilization event. The latter results are of physiological relevance as histidinemia is a human condition in which plasma His concentrations can reach up to 1.4 mM. Accordingly, the perturbation of the metabolism of Ni 2+ in the blood-organ system of histidinemia patients may contribute to the disease outcome.