Quantitative Evaluation of Urinary Porphyrins as a Measure of Kidney Mercury Content and Mercury Body Burden during Prolonged Methylmercury Exposure in Rats

Abstract

Changes in urinary porphyrin excretion patterns (porphyrin profiles) during prolonged mercury exposure are attributable to mercury accumulation in the kidney and to consequent effects of Hg2+ on renal porphyrin metabolism. In the present study, we evaluated the quantitative relationship of urinary porphyrin concentrations to mobilizable renal mercury content, using the metal chelator 2,3-dimercapto-1-propanesulfonic acid (DMPS) to modulate kidney mercury levels. Rats exposed to methylmercury hydroxide (MMH) at 10 ppm in drinking water for 6 weeks were treated with up to 3 consecutive doses of DMPS (100mg/kg, ip) at 72-h intervals. Consistent with previous findings, the concentrations of pentacarboxyl- (5-) and copro- (4-) porphyrins and of an atypical porphyrin specific to mercury exposure, precoproporphyrin, were significantly elevated in urine of MMH-exposed rats, compared with that of rats exposed to distilled water (dH2O) for the same period. Consecutive DMPS treatments of MMH-exposed rats significantly decreased kidney concentrations of total, as well as Hg2+ and CH3Hg+ species, and promoted increased urinary mercury excretion. Concomitantly, DMPS treatment decreased both kidney and urinary porphyrin concentrations, consistent with depletion of renal mercury levels. Regression analyses demonstrated a high correlation (r approximately 0.9) between prechelation urinary porphyrins and postchelation urinary mercury levels and also between prechelation urinary porphyrins and prechelation kidney mercury concentrations. These findings demonstrate that urinary porphyrin concentrations relate quantitatively to DMPS-mobilizable mercury in the kidney and, therefore, serve as a biochemical measure of renal mercury content.

A biomarker of mercury body-burden correlated with diagnostic domain specific clinical symptoms of autism spectrum disorder

“…Although this is not a direct measure of mercury in the brain, studies show that the brain and kidneys are target organs for mercury following mercury exposure. For example, Pingree et al (2001) gave rats methylmercury hydroxide (MMH) (10 ppm) in drinking water for 9 weeks and determined both inorganic (Hg2?) and organic (CH3Hg?)…”

Analysis of Urinary Porphyrins by High Performance Liquid Chromatography-Electrospray Ionization Mass Spectrometry

“…[2] Excessive production, accumulation, and excretion of porphyrins often result from metabolic aberration. Associated with abnormal heme biosynthesis, many diseases could be caused including porphyrias, [5] iron deficiency anemia, [6] liver disease, [7] and intoxication due to the overexposure to heavy metals, [8] environmental pollutants [9] , and alcohols [10] . Therefore, monitoring the composition and contents of certain porphyrins and establishing various porphyrin metabolic patterns might provide the references for the differentiation and diagnosis of porphyrin-related diseases.…”

A significant relationship between mercury exposure from dental amalgams and urinary porphyrins: a further assessment of the Casa Pia children’s dental amalgam trial

“…Previous studies have shown that urinary porphyrins can be particularly useful in measuring Hg exposure (Gonzalez-Ramirez et al 1995;Geier 2006, 2007;Geier et al 2009a, b;Kern et al 2010a,b;Woods, 1996;Pingree et al 2001). Urinary porphyrins are not a direct measure of Hg in the urine, but a measure of presence of Hg in the body (or Hg body-burden) by the level of disruption of the heme synthesis pathway that Hg causes.…”

“…The level of increase in these ''backlogged'' metabolites measured in the urine correlates with the level of disruption of this pathway and indicates the extent of Hg tissue burden. There is a high degree of statistical correlation between renal Hg burden and the urinary excretion of specific porphyrins (Pingree et al 2001). This correlation is consistently observed in animal models of Hg exposure; and the heme pathway is highly conserved across species (Gonzalez-Ramirez et al 1995).…”