Metabolism of porphyrins in experimental lead-, mercury-and cadmium intoxications

ABSTRACT

Subacute lead-, mercury- and cadmium intoxications were separately induced in 3 groups of adult male rabbits by dissolving the metals [16.6 mM] acetates in the drinking distilled water. A control group of rabbits, drinking distilled water was also included for comparison. After 6 weeks, blood total porphyrins were significantly elevated in both Pb- and Hg intoxicated rabbits and insignificantly elevated in Cd-intoxicated rabbits. Incubation of blood hemolysates from all rabbits with the porphyrin precursor delta-aminolevulinic acid [ALA] indicated excess porphyrin synthesis by blood of Pb- intoxicated and normal synthesis of Hg- and Cd-intoxicated rabbits. Fractionation of the synthesized porphyrins revealed the presence of uroporphyrin [URO, 8 COOH], coproporphyrin [CP, 4 COOH] and porotoorphyrin [PP, 2 COOH] as well as 7 COOH-, 6 COOH-and 5 COOH-prophyrins in varying levels in each metal intoxication. The results of the decarboxylation of URO to CP prompted us to postulate the presence of at least 2 URO-decarboxylases. Excess urine and fecal porpyrin excretion was observed but the excretion was earlier in Pb-intoxication than in Hg- and Cd-intoxications. Total porphyrins in the liver and kidney were elevated in Pb-intoxication only. However, all porphyrin fractions were detected and quantitated in both tissues extracted from all rabbits. The role of kidney in the porphyrin of Pb and other metals poisoning is discussed and a mechanism for the hypersynthesis of porphyrins by kidney of Pb-intoxicated rabbits is presented