Comparative evaluation of macrocyclic drugs and their linear counterparts in preventing nickel toxicity in mice
Titel:
Comparative evaluation of macrocyclic drugs and their linear counterparts in preventing nickel toxicity in mice
Auteur:
Srivastava, Amita Katiyar, S. S. Behari, Jai Raj Srivastava, Sanjay K. Hasan, S. K. Srivastava, R. C.
Verschenen in:
Journal of environmental science and health. Part A, Toxic/hazardous substances & environmental engineering
Paginering:
Jaargang 24 (1989) nr. 1 pagina's 77-86
Jaar:
1989-01
Inhoud:
The efficacy of a few macrocyclic drugs, viz. 1,4,8,11-tetraaza-cyclo-tetradecane (cyclam); 5,7,7', 12,14,14'-hexamethyl-l, 4,8,11-tetraaza-cy'clo-tetra-decane (cyclam-S); 1,4,8,11-tetrahydroxyethyl-1,4,8,11 -tetraazacyclo-tetradecane (THEC) and 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetrade-cane (TMC) and their linear counterparts, viz. triethylene-tetramine (TETA) and NN'-bis-(2-aminoethyl)-l,3-propane diamine (TET) was examined for prevention of mortality and nickel uptake in the body organs of nickel poisoned mice (at the level of 250 μ mole/kg i.p. of NiCl2 i.e. LD90 or greater), when administered at various molar ratios of nickel vs. drug. Amongst the chelating drugs the most effective antidote was cyclam followed by cyclam-S, TETA, THEC, TMC and TET. All the chelating drugs with exception to THEC demonstrated higher survival rate and low nickel body burden with increase in the drug concentration. Test for significant difference between a pair of proportions at various Nirdrug ratios further revealed that cyclam yielded a significantly higher survival rate than the other chelating drugs studied.