Urinary Coproporphyrin

Other studies have suggested that lead may also impair the transport of coproporphyrinogen into mitochondria subsequent to its synthesis by uroporphyrinogen decarboxylase in the cytoplasmic portion of the cell (Rossi et al. 1993) (Fig. 5). The processes by which coproporphyrinogen is transported into the mitochondrion or through the outer to inner membrane spaces are not defined. If lead were to interfere with these processes, the 

Finally, experimental studies from this laboratory (Simmonds et al. 1994) have shown that urinary coproporphyrin levels are as highly correlated with renal lead levels (r = 0.79) as with blood lead levels (r = 0.75) after 3 weeks following initiation of prolonged lead exposure in rats. These findings suggest that elevated urinary coproporphyrin may represent kidney lead accumulation leading to nephrotoxicity, and, hence, may be useful in diagnostic evaluation. Further studies are required to substantiate this possibility. 

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NS (general population) Hematological Increased urinary coproporphyrin 35 (children 40 (adults) EPA 1986a... 

An increase in urinary coproporphyrin has long been recognized in workers and children with lead poisoning and used as an indicator of excessive exposure to lead (EPA 1986a). EPA (1986a) identified a LOAEL for elevated coproporphyrin at a PbB level of 40 pg/dL for adults and 35 pg/dL for children, but did not present the basis for this conclusion. 

M (decreased erythrocyte ALAD activity increase urinary coproporphyrins)... 

W) ZPP/heme ratio increased urinary coproporphyrins PbAc... 

Stomach aches, constipation, and nausea Urinary coproporphyrin increase Vomiting... 

Frank, M., Doss, M., de Carvalho, D.G. Diagnostic and pathogenetic imphcations of urinary coproporphyrin excretion in the Dubin-Johnson syndrome. Hepato-gastroenterol. 1990 37 147-151... 

Shimizu, Y., Naruto, H., Ida, S., Kohakura, M. Urinary coproporphyrin isomers in Rotor s syndrome. A study in eight families. Hepatology 1981 1 173-178... 

Rotor syndrome is another form of conjugated hyperbilirubinemia similar to Dubin-Johnson syndrome but without pigment in the liver. The gallbladder is seen on intravenous cholecystography. Total urinary coproporphyrins are elevated, with about two thirds being coproporphyrin I. The prognosis is excellent. 

Rocchi E, Gibertini P, Santunione V, Balli F, Ventura E. Faecal and urinary coproporphyrin isomers in biliary atresia and neonatal hepatitis. Ric Clin Lab 1980 10 509-10. 

In Rotor s syndrome, patients lack the hepatic pigment but have urinary coproporphyrin levels 2.5-5 times greater than normal. Coproporphyrin type I is increased relative to the type III isomer but not as much as in Dubin-Johnson syndrome. Intrahepatic storage of sulfobromophthalein is... 

M (increased relative liver weight, lipid content and increased urinary coproporphyrin)... 

Commercial PCB Mixtures. Urinary coproporphyrin levels were increased in rats that ingested 0.3 or 1.5 mg/kg/day Aroclor 1242 in the diet for 2-6 months (Bruckner et al. 1974). Rats treated with 5 mg/kg/day Aroclor 1254 in the diet had maximum increases in liver microsomal P-450 concentration and liver weight after 1 week, but onset of porphyria and induction of 5-aminolevulinic acid (ALA) synthetase was delayed until 2-7 months of treatment (Goldstein et al. 1974). A marked accumulation of uroporphyrins occurred in the liver, and urinary excretion of coproporphyrin and other porphyrins was increased the largest increase was in uroporphyrins. The uroporphyrins in the liver and urine of the treated rats consisted primarily of 8- and 7-carboxyporphyrins. 

Chang KJ, Hsieh KH, Lee TP, et al. 1980. Studies on patients with polychlorinated biphenyl poisoning 2. Determination of urinary coproporphyrin, uroporphyrin, y-aminolevulinic acid and porphobilinogen. Res Commun Chem Pathol Pharmacol 30 547-554. 

The other indirect measures which can be used to monitor lead exposure are changes in the levels of a range of enzymes and metabolites involved in the synthesis and operation of haem. Thus, increases in the levels of free erythrocyte protoporphyrin (FEP) or of zinc protoporphyrin (ZPP) in blood can be associated with increased levels of lead in blood, as can decreased levels of activity of the enzyme delta-aminolaevulinic acid ddiydratase (ALAD). Similarly increases in the levels of urinary coproporphyrin (CP) and urinary aminolaevulinic acid (ALAU) also reflect increased lead exposure. These measures are not, however, always reliable since they can be affected by other factors, for exattqrle ZPP may be increased by iron deficiency. Measurements of these parameters tend, therefore, to be us only in conjunction with, and to provide supplementary data to, blood lead measurements. 

Shortened erythrocyte survival Battery and smelter workers (n = 17) and controls (n = 4) Urinary coproporphyrin >500 pg/L Erythrocyte survival was 101 days in workers vs 120 days in controls. Clinically important outcome. Hemberg et al. 1967... 

Chisolm Jr., J.J., Harrison, H.E., 1956. Quantitative urinary coproporphyrin excretion and its relation to edathemil calcium disodium administration in children with acute lead intoxication. J. Clin. Invest. 35, 1131—1138. 

Accumulation of urinary coproporphyrin has also been reported, principally in highly exposed children and lead workers and mainly in the older literature (Chisolm and Harrison, 1956 Haeger-Aronsen, 1960). CP accumulation, from inhibition by lead of coproporphyrin utilization in subsequent formation of protoporphyrin, is a relatively late responder to Pb exposure in both children and workers, and the association of urinary CP with PbB principally is seen at PbB values 40 pg/dl. It has rarely been used in recent... 

Bowers et al. 1992) have shown that the levels of total coproporphyrin in either spot urine samples or 24-h collections fall within a relatively well defined range (Table 1). In view of the sensitivity and magnitude of the coproporphyrin response to lead exposure as demonstrated from animal as well as human studies, it is likely that values exceeding the normal range could be readily detected among lead-exposed subjects if employed in populations in which the normal intra- and interindividual variability is first well defined. Under these circumstances the sensitivity of urinary coproporphyrin may equal or exceed that of erythrocyte ALAD as a measure of low level lead exposure. 

In studies in vivo (Woods and Fowler 1977 Woods and Southern 1989), treatment of male Sprague Dawley rats with methyl mercury hydroxide (MMH) for 6 weeks at 0.6 or 1.2mg/kg per day by drinking water produced a pronounced coproporphyrinuria characterized by a dose-related increase in the urinary coproporphyrin concentration up to 20 times control levels. Renal coprogen oxidase activity was depressed by as much as 56% of the control value 3 weeks after initiation of MMH treatment, whereas hepatic coprogen oxidase was not affected. Depression of renal coprogen oxidase activity correlated closely with increasing mercury levels in the kidney, suggesting that the interaction of Hg " either with the enzyme itself... 

Henderson MJ, Toothill C (1983) Urinary coproporphyrin in lead intoxication a study in the rabbit. Clin Sci 65 527-532... 

Disease Urinary ALA Urinary PBG Urinary uroporphyrin Urinary coproporphyrins ALA-de- hydratase Peripheral red blood cells Further analyses... 

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