Urinary coproporphyrin in lead intoxication: a study in the rabbit.
Lead acetate was administered to adult New Zealand White rabbits in their drinking water. Their mean blood lead level rose to 4.5 mumol/l within a week and then remained relatively constant. The rabbits developed a marked coproporphyrinuria. Plasma levels of coproporphyrin increased but not in proportion to the urine excretion. Thus the renal clearance of coproporphyrin rose from a mean of 1.8 ml/min to 32.2 ml/min whilst creatinine clearance remained constant. The concentration of coproporphyrin in renal venous blood from control rabbits was found to be slightly lower than that in arterial blood. In the lead intoxicated rabbits the concentration of coproporphyrin in renal venous blood was approximately three times higher than the arterial concentration. Significantly higher levels of lead, porphobilinogen, uroporphyrin, coproporphyrin and protoporphyrin were found in renal tissue than in brain, heart or liver. Renal tissue homogenates from control rabbits were able to synthesize porphobilinogen, uroporphyrin, coproporphyrin and protoporphyrin when incubated with 5-aminolaevulinic acid. Renal tissue from lead intoxicated rabbits was also able to synthesize these haem precursors although at a reduced rate. Three enzymes from the haem biosynthetic pathway were assayed in renal mitochondria. Compared with those from controls, mitochondria from lead intoxicated rabbits showed no significant difference in ferrochelatase activities, but the activities of coproporphyrinogen oxidase were decreased, and those of 5-aminolaevulinate synthase were increased. It was concluded that a large portion of the excess coproporphyrin excreted by the lead intoxicated rabbits was of renal origin.
D000818:Animals; D003306:Coproporphyrins / Q000097:blood / Q000652:urine*; D005260:Female; D007668:Kidney / Q000378:metabolism; D007854:Lead / Q000378:metabolism; D007855:Lead Poisoning / Q000378:metabolism*; D011166:Porphyrins / Q000652:urine*; D011817:Rabbits; D014018:Tissue Distribution
D003306:Coproporphyrins; D011166:Porphyrins; D007854:Lead