GLUTATHIONE, ALBUMIN, CYSTEINE, AND CYS-GLY EFFECTS ON TOXICITY AND ACCUMULATION OF MERCURIC CHLORIDE IN LLC-PK1 CELLS

• Published in: Journal of Toxicology and Environmental Health, Part A Part A, 1999-08, Vol.57 (7), p.489-505
• Main Authors: DIVINE, K. K, AYALA-FIERRO, F, BARBER, D. S, CARTER, D. E
• Format: Article
• Language: English
• Subjects: Albumins - metabolism; Animals; Biological and medical sciences; Cells, Cultured; Chemical and industrial products toxicology. Toxic occupational diseases; Cysteine - metabolism; Dipeptides - metabolism; Environmental Pollutants - toxicity; Glutathione - metabolism; Kidney - cytology; Kidney - drug effects; LLC-PK1 Cells - drug effects; Medical sciences; Mercuric Chloride - toxicity; Metals and various inorganic compounds; Sulfhydryl Compounds - metabolism; Swine; Toxicology
• ISSN: 1528-7394; 0098-4108; 1087-2620
• DOI: 10.1080/009841099157566

Speciation plays a profound if not dominant role in both transport and toxicity of Hg(II). Hg(II) has a high affinity for sulfhydryl groups. The formation constant for Hg2+ and the anionic form of a sulfhydryl group R-S- is 1010 higher than that for the carboxyl or amino groups. The kidneys are the target organ for Hg(II) toxicity and the primary site of Hg(II) accumulation. Sulfhydryl groups have been implicated in both transport and nephrotoxicity; however, the role endogenous thiol compounds play in these parameters is not clear. The roles that albumin, glutathione, and the glutathione-derived complexes cysteinylglycine and L-cysteine play in toxicity and accumulation of HgCl2 were studied in LLC-PK1 cells incubated with different Hg(II):thiol ratios. In cysteine-containing medium, almost all 1:2 Hg(II):thiol complexes protected against Hg(II) toxicity up to 120 muM Hg, increased membrane-bound Hg(II), and decreased intracellular Hg(II) accumulation. In cysteine-free medium, all 1:1 Hg(II):thiol complexes were as toxic as uncomplexed Hg(II), and almost all 1:2 Hg(II):thiol complexes protected at 20 muM Hg, except albumin, which protected at 20 muM Hg. In cysteine-free but cystine-containing medium, two 1:1 Hg(II):thiol complexes were toxic at 80 muM Hg and two provided complete protection. All 1:2 complexes provided protection at 80-160 muM Hg. This investigation used defined media to demonstrate that mercury cytotoxicity in LLC-PK1 cells was dependent on Hg(II) concentration, the ligand, and the presence of a cysteine source for the cells. These effects were only partially explained by intracellular Hg(II) levels.