Uroporphyrin accumulation in the bone makrow of rats exposed to lead

Christenson, W. R.; Reddy, Vijayapal R.; Piper, Walter N.

doi:10.1016/0006-2952(85)90299-0

Cited by 3 publications

(3 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Efect of lead on uroporphyrin I andprotoporphyrin content in rat bone marrow. Preliminary findings from this laboratory (Christenson et al, 1985) have indicated that uroporphyrin I accumulates in the bone marrow of lead poisoned rats. These findings would suggest a sensitivity of COSYN to lead.…”

Section: Resultsmentioning

confidence: 94%

“…E#ect of lead, nitrous oxide, and their combination on uroporphyrin and polyglutamated folate content in rat bone marrow. The report of a polyglutamated folate moiety, functioning as a possible coenzyme to COSYN (Kohashi et al, 1984) and the observation that URO I accumulation, a condition indicative of COSYN inhibition, occurs in the bone marrow of lead poisoned experimental rats (Christenson et al, 1985) and rabbits (Schmid et al, 1952) raised the question as to whether the toxicity of lead toward COSYN might be modulated by the folate status of the tissue. To examine this question, rats were exposed to nitrous oxide at 4 hr/day for 7 days.…”

Section: Figmentioning

confidence: 99%

“…The rare disease of congenital erythropoietic porphyria is believed to be due to an inherited enzymatic defect in uroporphyrinogen III cosynthase, causing excretion of excess URO I and COPRO I in the urine (Deybach et al,198 1). In addition, URO I accumulation has also been reported in the bone marrow of lead poisoned rats (Christenson et al, 1985) and rabbits (Schmid et al, 1952). These findings, together with a study by Kohashi et al (1984) indicating that COSYN may require a reduced pteroylpolyglutamate coenzyme in order to facilitate UROGEN III biosynthesis, prompted us to investigate the effect of folate deficiency in regulating the toxic response of COSYN to lead in the bone marrow of the rat.…”

mentioning

confidence: 94%

See 2 more Smart Citations

Evidence for pteridine regulation of lead-mediated inhibition of uroporphyrinogen and heme formation in rat bone marrow

Christenson

Bestervelt

Piper

1992

Toxicology and Applied Pharmacology

Self Cite

View full text Add to dashboard Cite

Uroporphyrin I (URO I) accumulation has been reported in the bone marrow of rats exposed to lead, suggesting a sensitivity of uroporphyrinogen III cosynthase (COSYN) to this heavy metal. Furthermore, it has been reported that a polyglutamated folate derivative may serve as a coenzyme for the catalytic action of hepatic uroporphyrinogen III cosynthase. These findings raised the question of whether depletion of polyglutamated folate could enhance the susceptibility of bone marrow COSYN to lead and potentially interfere with the formation of heme. Nitrous oxide, an anesthetic agent capable of causing bone marrow tetrahydrofolate deficiency, depressed total bone marrow polyglutamated folate content by 42% with significant reductions in all three chain lengths (5-7) identified in the bone marrow during an exposure period of 7 days at 4 hr/day. Lead acetate (15 mg/kg) administered by ip injection at Days 0 and 2 during a 7-day exposure to nitrous oxide resulted in an 84% increase of bone marrow URO I content, which was markedly higher than the increases of 22 and 38% seen with sole administration of lead or nitrous oxide, respectively. The combination of agents also produced a 48% rise in COPRO I, a 39 and 43% decrease in COPRO III and protoporphyrin, respectively, and a 42% decline in the activity of microsomal 7-ethoxycoumarin O-deethylase, which is hemoprotein, cytochrome P-450 mediated. Heme oxygenase activity was not altered by nitrous oxide, lead, or their combination. These results suggest that bone marrow folate deficiency may render COSYN more sensitive to lead as characterized by increased uroporphyrin I and coproporphyrin I isomer content, decreased coproporphyrin III and protoporphyrin content, and depressed microsomal hemoprotein, cytochrome P-450-mediated drug-metabolizing capability.

show abstract

Section: Resultsmentioning

confidence: 94%