Relative efficacy of chelating agents on excretion and tissue distribution of manganese in mice.

Abstract

The effect of repeated parenteral administration of a number of structurally diverse chelating agents on the excretion and tissue distribution of manganese was assessed in mice following 4 weeks of manganese exposure. Males Swiss mice received s.c. injections of manganese(II) chloride tetrahydrate (8.9 mg Mn kg-1 body wt.) for 4 weeks (5 days per week). After the end of this exposure period, cyclohexanediaminetetraacetic acid (CDTA), ethyleneglycol-bis-(beta-aminoethylether)-N,N-tetraacetic acid (EGTA), N-(2-hydroxyethyl)ethylenediamine triacetic acid (HEDTA), isonicotinyl hydrazine (INH), L-dopa, sodium 4.5-dihydroxy-1.3-benzenedisulphonate (Tiron), p-aminosalicylic acid (PAS) or 0.9% saline (control group) were given i.p. for five consecutive days. The doses of the chelators were approximately equal to one-eighth of their respective LD50 values. Urine and faeces were daily collected for 5 days. Twenty-four hours after the final chelator injection, mice were killed and manganese concentrations were determined in various tissues. Although CDTA, EGTA and HEDTA significantly enhanced the elimination of manganese into urine, none of the chelators increased faecal excretion. Tissue concentrations of manganese were significantly reduced only by CDTA. According to these results, among the compounds tested only CDTA would mobilize effectively manganese in manganese-loaded mice.