Porphyrin mercury exposure

Woods JS. 1996. Altered porphyrin metabolism as a biomarker of mercury exposure and toxicity. Can J Physiol Pharmacol 74(2) 210-215. 

Woods JS, Martin MD, Naleway CA, Echeverria D. Urinary porphyrin profiles as a biomarker of mercury exposure Studies on dentists with occupational exposure to mercury vapour. J Toxicol Environ Health 1993 40 235-46. 

The mechanism underlying the accumulation of 5- and 4-carboxyl porphyrins observed during mercury exposure has been shown to involve mercuric ion (Hg " ) (or CH3Hg )-directed impairment of renal coprogen metabolism (Woods and Southern 1989). Coprogen oxidase from kidney is highly sensitive to inhibition by Hg " in vitro and in vivo. Woods and Southern (1989) assessed the effects of Hg " at various concentrations on coprogen oxidase in mitochondrial preparations from rat liver and kidney in vitro. The activity of the enzyme from both tissues was inhibited in a dose-related manner, with activity reduced to approximately 50% of control levels by Hg at 100//M in reaction mixtures. 

Of additional interest with regard to the porphyrinogenic action of mercury is the observation from animal studies that prolonged mercury exposure is characterized by the excretion in the urine of an atypical porphyrin, not normally found in urine of unexposed subjects, which elutes on HPLC approximately mid-way between the 5- and 4-carboxyl porphyrins (Woods et al. 1991). This porphyrin has been referred to as precopro-porphyrin in several previous publications (Bowers et al. 1992 Woods et al. 1993) and appears to be unique to mercury exposure. Absorption and electrospray ionizing mass spectroscopic analyses have suggested that this atypical porphyrin shares structural properties of a keto derivative of isocoproporphyrin. However, the precise structural characteristics as well as the biochemical etiology of this porphyrin remain to be established. This porphyrin has been detected in urine both of mercury-exposed animals and human subjects (Woods et al. 1991, 1993). 

The efficacy of urinary porphyrin profiles as a biomarker of exposures to metals other than lead in human populations is less well established. Studies on dentists with occupational mercury exposure have provided preliminary evidence of the potential utility of urinary porphyrin changes as a biomarker of low-level mercury exposure in human subjects (Woods et al. 1993), and further studies have demonstrated their efficacy as a measure of cumulative effects of mercury on specific tests of neurobehavioral function (Echeverria... 

Fowler BA, Mahaffey KR (1978) Interaction among lead, cadmium and arsenic in relation to porphyrin excretion patterns. Environ Health Perspect 25 87-90 Fowler BA, Woods JS (1977) Ultrastructural and biochemical changes in renal mitochondria following chronic oral methyl mercury exposure the relationship to renal function. Exp Mol Pathol 27 403-412 Fowler BA, Kimmel CA, Woods JS, McConnell EE, Grant LD (1980) Chronic low level toxicity of lead in the rat. III. An integrated assessment of long-term toxicity with special reference to the kidney. Toxicol Appl Pharmacol 56 59-77... 

Woods JS, Martin MD, Naleway GA, Echeverria D (1993) Urinary porphyrin profiles as a biomarker of mercury exposure studies in dentists with occupational exposure to mercury vapor. J Toxicol Environ Health 40 239-250 Yamanaka K, Hoshino M, Okamoto M, Sawamura R, Hasegawa A, Okada S (1990) Induction of DNA damage by dimethylarsine, a metabolite of inorganic arsenics, is for the major part likely due to its peroxyl radical. Biochem Biophys Res Gommun 168 58-64... 

This profile is observed at variable dose levels, as well as up to at least 40 weeks after cessation of exposure. The time course of the profile during prolonged treatment is closely associated with divalent inorganic mercury (Hg+2), suggesting that the effects are mediated by this cation because it inhibits the heme pathway (Woods et al. 1991). Specificity may be a problem unless the porphyrin levels are analyzed at the same time as urinary mercury measurements. 

Biochemical indicators of possible renal dysfunction (increased urinary NAG levels, and elevated porphyrins) have been associated with increased urinary levels of mercury (Rosenman et al. 1986 Wada et al. 1969 Woods 1996). Functional indicators of adverse neurological effects (reduced nerve conduction velocity, prolonged nerve latency, increased tremor frequency, increased reaction time, reduced hand-eye coordination, and performance on memory and verbal intelligence tests) have also been correlated with increased urinary levels of mercury (Levine et al. 1982 Piikivi et al. 1984 Smith et al. 1970, 1983 Verberk et al. 1986 Vroom and Greer 1972 Williamson et al. 1982). Decreased nerve conduction velocity has been correlated with increased tissue levels of mercury (Shapiro et al. 1982). These biomarkers are not specific for mercury and may be induced by exposure to other metals and... 

Woods JS, Bowers MA, Davis HA. 1991. 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. Toxicol Appl Pharmacol 110(3) 464-476. 

This chapter describes the mechanistic basis of metal-induced alterations in porphyrin metabolism as derived from experimental studies and summarizes the evidence supporting the utility of porphyrin measurements as a biomarker of exposure and effects of specific metals in human subjects, with specific emphasis on lead, mercury, and arsenic. Some perspectives and research needs regarding the use of porphyrin measurements as biomarkers of metal exposures and effects in human populations are also presented. 

The distinctive porphyrin patterns associated with exposure of animals to lead, mercury, and arsenic, compared with the normal profile, are depicted in Fig. 8. Changes in urinary porphyrin patterns associated with these and other metals offer promise as biomarkers of metal exposures and potential toxicity in humans from several perspectives. As biological responses to metal effects in target tissues, changes in porphyrin patterns are indicative of the internal concentration of metals in target tissues, and clear dose-response and time-related effects of metals with respect to development of porphyrin profile changes have been demonstrated in animal studies. These findings... 

Fig. 8. Urinary porphyrin profiles from Fischer-344 rats showing distinctly altered porphyrin excretion patterns associated with prolonged mercury, arsenic, and lead exposures. Abscissa represents HPLC elution time (minutes)...

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