Urinary porphyrin profiles as biomarkers of trace metal exposure and toxicity: studies on urinary porphyrin excretion patterns in rats during prolonged exposure to methyl mercury.
Studies were conducted to define the specific changes in the urinary porphyrin excretion pattern (porphyrin profile) and the time course of those changes in rats exposed to mercury as methyl mercury hydroxide (MMH) at 5 or 10 ppm in the drinking water for up to 30 weeks. The urinary porphyrin profile elicited by MMH is uniquely characterized by highly elevated levels of 4- and 5-carboxyl porphyrins, and of a third atypical porphyrin with as yet undetermined chemical characteristics. Changes in the porphyrin profile were observed as early as 1 or 2 weeks following initiation of exposure to MMH at 10 or 5 ppm, respectively, and were sustained as long as 40 weeks following cessation of MMH treatment. The magnitude of the urinary porphyrin profile at either MMH dose level increased progressively during the course of mercury treatment and was highly correlated with the renal mercury concentration. A subsequent decline in the magnitude of the urinary porphyrin profile in animals exposed to 10 ppm MMH for more than 10 weeks was associated with the accumulation of high levels of Hg2+ in kidney cells and loss of renal functional status. These findings demonstrate that mercury elicits a unique change in the urinary porphyrin excretion pattern which is related to the dose and duration of mercury treatment. The association of urinary porphyrin excretion rates with renal mercury content and functional status suggests that urinary porphyrin profiles may serve as a useful biomarker of mercury accumulation and nephrotoxicity during prolonged mercury exposure.
Woods
J S
JS
Department of Environmental Health, University of Washington, Seattle 98195.
Bowers
M A
MA
Davis
H A
HA
D000818:Animals; D015415:Biomarkers / Q000652:urine; D001835:Body Weight / Q000187:drug effects; D004326:Drinking; D007668:Kidney / Q000378:metabolism; D008297:Male; D008628:Mercury / Q000493:pharmacokinetics / Q000652:urine; D008767:Methylmercury Compounds / Q000009:adverse effects*; D011166:Porphyrins / Q000652:urine*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D015415:Biomarkers; D008767:Methylmercury Compounds; D011166:Porphyrins; C034350:pentacarboxylic porphyrin; C020771:methylmercury hydroxide; D008628:Mercury