The Effect of N–acetyJated DL–penicillamine and DL–homocysteine Thiolactone on the Mercury Distribution in Adult Rats,Rat Foetuses and Macaca Monkeys after Exposure to Methyl Mercuric Chloride

Abstract The distribution and excretion of mercury was studied in pregnant rats, given a single intravenous dose of 2 μmol/kg of CH₃²⁰³HgCl on the 13th day of pregnancy. Oral treatment for one week with N–acetyl–DL–penicillamine (4 mmol/kg per day) increased the mercury excretion in faeces (from 45 to 120 nmol) and urine (from 9 to 160 nmol). Such treatment mobilized mercury from all the organs tested, and the foetal and maternal brain levels of mercury were decreased to 1/5 and 1/3 of the controls, respectively. A four–day period of treatment with N–acetyl–DL–penicillamine started three days after the injection of methyl mercury reduced the foetal and maternal brain levels to 1/2 and 2/3 of the controls, respectively. The rapid removal of metal deposits following treatment with N–acetyl–DL–penicillamine is attributed to a free penetration of the complexing thiol into the tissue cells in question. No signs of toxicity were detected in monkeys given an effective daily dose of the agent (4 mmol/kg) for 6 days. In contrast N–acetyl–DL–homocysteine thiolactone was found to be toxic in the monkeys. In addition, the latter agent was ineffective in increasing the mercury elimination from the brains of monkeys, rats and rat foetuses.     

Mobilization of Methyl Mercury in Vivo and in Vitro using N–acetyl–DL–penicillamine and other Complexing Agents

Abstract The distribution and excretion of mercury was studied in mice given a single intravenous dose of 5 umol/kg of methyl mercuric chloride. Oral treatment with N–acetyl–DL–penicillamine (3 mmol/kg per day) removed more mercury from the brain and from the whole body than the corresponding treatment with other complexing agents, and it was also effective on delayed treatment. Even more mercury was removed into the faeces and the urine, by higher doses of N–acetyl–DL–penicillamine, and 4 days of treatment with 27 mmol/kg per day of this compound did not give rise to any significant toxic symptoms in the mice. In vitro experiments showed that the chemical affinity of N–acetyl–DL–penicillamine for methyl mercury was higher than that of the other thiols tested, except D–penicillamine. In contrast to the latter, N–acetyl–DL–penicillamine easily penetrated the cellular membranes, and therefore rapidly removed a substantial fraction of methyl mercury from the blood cells. It is assumed that N–acetyl–DL–penicillamine can reduce the mercury concentration in brain cells by converting the intracellularly non–diffusible methyl mercury into a freely diffusible complex.     

N-acetylpenicillamine potentiated excretion of methyl mercury in rat bile: influence of S-methylcysteine

N-acetylpenicillamine, 5 mmol/kg body weight increased biliary excretion of methyl mercury more than three fold. Upon simultaneous administration of the same dose of N-acetylpenicillamine and 2,5 mmol/kg body weight of S-methylcysteine biliary excretion of methyl mercury increased only 1.5 fold. In both cases biliary sulfhydryl concentration increased to the same extent, about 5 fold. Decreased biliary excretion of methyl mercury, as a result of liver depletion of reduced glutathione by cyclohexene oxide, could be restored by N-acetylpenicillamine. This restoration could be depressed by S-methylcysteine. The experiments undertaken indicate that N-acetylpenicillamine potentiated methyl mercury excretion occurs by a glutathione S-transferase dependent mechanism. Bile, collected after successive administration of methyl mercuric chloride, cyclohexene oxide, S-methylcysteine and N-acetylpenicillamine contained the methyl mercuric derivatives of N-acetylpenicillamine and glutathione together with other methyl mercury carrying components not present in control bile. Whether these components play any role in the mechanism of N-acetylpenicillamine potentiated methyl mercury excretion cannot be stated from the present investigation.     

Slow biliary elimination of methyl mercury in the marine elasmobranchs, Raja erinacea and Squalus acanthias

The present study examined the ability of two marine elasmobranchs (Raja erinacea, little skate, and Squalus acanthias, spiny dogfish shark) to excrete methyl mercury into bile, a major excretory route in mammals. 203Hg-labeled methyl mercury chloride was administered via the caudal vein, and bile collected through exteriorized cannulas in the free swimming fish. Skates and dogfish sharks excreted only a small fraction of the 203Hg into bile over a 3-day period: in the skate, the 3-day cumulative excretion (as a % of dose) was 0.44 +/- 0.10 (n = 4, +/- SD), 0.71 +/- 0.23 (n = 6), and 1.00 +/- 0.34(n = 4) for doses of 1, 5, and 20 mumol/kg, respectively, while the shark excreted only 0.15 +/- 0.15% (n = 8) at a dose of 5 mumol/kg. As in mammals, the availability of hepatic and biliary glutathione was a determinant of the biliary excretion of methyl mercury in these species: the administration of sulfobromophthalein, a compound known to inhibit both glutathione and methyl mercury excretion in rats, or of L-buthionine-S,R-sulfoximine, an inhibitor of glutathione biosynthesis, decreased the biliary excretion of both glutathione and mercury in the skate. The slow hepatic excretory process for methyl mercury in the skate and shark was attributed to an inordinately slow rate of bile formation: from 1 to 4 ml/kg X day. An inefficient biliary excretory process in fish may account in part for the long biological half-times for methyl mercury in marine species.     

7V-Acetylpenicillamine Potentiated Excretion of Methyl Mercury in Rat Bile: Influence of S-Methylcysteine

Abstract: N-acetylpenicillamine, 5 mmol/kg body weight increased biliary excretion of methyl mercury more than three fold. Upon simultaneous administration of the same dose of N-acetylpenicillamine and 2,5 mmol/kg body weight of S-methylcysteine biliary excretion of methyl mercury increased only 1.5 fold. In both cases biliary sulfhydryl concentration increased to the same extent, about 5 fold. Decreased biliary excretion of methyl mercury, as a result of liver depletion of reduced glutathione by cyclohexene oxide, could be restored by N-acetylpenicillamine. This restoration could be depressed by S-methylcysteine. The experiments undertaken indicate that N-acetylpenicillamine potentiated methyl mercury excretion occurs by a glutathione S-transferase dependent mechanism. Bile, collected after successive administration of methyl mercuric chloride, cyclohexene oxide, S-methylcysteine and N-acetylpenicillamine contained the methyl mercuric derivatives of N-acetylpenicillamine and glutathione together with other methyl mercury carrying components not present in control bile. Whether these components play any role in the mechanism of N-acetylpenicillamine potentiated methyl mercury excretion cannot be stated from the present investigation.     

Renal functional correlates of methyl mercury intoxication: interaction with acute mercuric chloride toxicity.

To determine the effect of methyl mercury and its possible interaction with mercuric chloride on renal function, male Sprague-Dawley rats were treated with methyl mercuric chloride (1 mg/kg per day × 20 days ip) and/or mercuric chloride (1 mg/kg ip at Day 20) in a 2 × 2 factorial experimental design. Methyl mercury depressed urine osmolality and N-methylnicotinamide (NMN) uptake by renal cortical slices but did not affect the uptake of p-aminohippurate (PAH), blood urea nitrogen concentration (BUN), urine volume, or body weight. Urinary excretion of the lysosomal enzymes, β-galactosidase and acid phosphatase, appeared to be decreased, but excretion of the brush border enzyme, alkaline phosphatase, was not affected. Mercuric chloride treatment increased enzyme excretion, BUN, and uptake of NMN by renal cortical slices, while it decreased PAH uptake and urine osmolality, BUN concentration was further increased by combined treatment, yielding the only significant treatment interaction between methyl mercury and mercuric chloride. Prostaglandin E₂ synthesis and release by renal medullary tissue in vitro was not depressed by methyl mercuric chloride pretreatment nor was renal ammoniagenesis or gluconeogenesis. The effects of methyl mercury upon lysosomal enzyme excretion and NMN accumulation are suggestive of lysosomal and mitochondrial dysfunction. The failure to detect significant interaction between methyl mercury and mercuric chloride indicates that methyl mercury neither potentiates nor protects against acute mercuric chloride toxicity at this time and dose.     

The Effect of Selenium on the Biliary Excretion and Organ Distribution of Mercury in the Rat after Exposure to Methyl Mercuric Chloride

Abstract The influence of selenium compounds on the biliary excretion and the organ distribution of mercury after injection of methyl mercuric chloride (4 μmol/kg) have been tested. Selenite, seleno-di-N-acetylglycine and seleno-methionine strongly inhibited the biliary excretion of mercury. Selenite even in a molar dose of 1/40 of the methyl mercury dose inhibited the biliary excretion of mercury. The less toxic seleno-di-N-acetylglycine was needed in larger molar doses and did not act as rapidly as selenite. Biliary excreted methyl mercury is known to be partly reabsorbed in the gut. Subsequently a part of it is deposited in the kidneys since drainage of the bile lowered the kidney content of mercury. Rats given selenium compounds in combination with bile drainage showed further reduction of the kidney mercury content than bile duct drainage alone. Thus the demonstrated lowering effect of selenium compounds on the kidney mercury content cannot be completely explained by an inhibition of biliary excretion of mercury. The mercury concentration in the brain was increased by the selenium compounds; the effect being dependent of the selenium dose reaching a maximum at an equimolar selenite - to methyl mercury dose ratio. The mechanisms by which selenium influences the methyl mercury kinetics are discussed.     

The effect of selenium on the biliary excretion and organ distribution of mercury in the rat after exposure to methyl mercuric chloride.

The influence of selenium compounds on the biliary excretion and the organ distribution of mercury after injection of methyl mercuric chloride (4 mumol/kg) have been tested. Selenite, seleno-di-N-acetylglycine and seleno-methionine strongly inhibited the biliary excretion of mercury. Selenite even in a molar dose of 1/40 of the methyl mercury dose inhibited the biliary excretion of mercury. The less toxic seleno-di-N-acetylglycine was needed in larger molar doses and did not act as rapidly as selenite. Biliary excreted methyl mercury is known to be partly reabsorbed in the gut. Subsequently a part of it is deposited in the kidneys since drainage of the bile lowered the kidney content of mercury. Rats given selenium compounds in combination with bile drainage showed further reduction of the kidney mercury content than bile duct drainage alone. Thus the demonstrated lowering effect of selenium compounds on the kidney mercury content cannot be completely explained by an inhibition of biliary excretion of mercury. The mercury concentration in the brain was increased by the selenium compounds; the effect being dependent of the selenium dose reaching a maximum at an equimolar selenite--to methyl mercury dose ratio. The mechanisms by which selenium influences the methyl mercury kinetics are discussed.     

Reduced Decomposition and Faecal Excretion of Methyl Mercury in Caecum-Resected Mice

Abstract: Decomposition and faecal excretion of methyl mercury in caecum-resected mice was investigated in order to elucidate the role of the caecum in metabolizing methyl mercury. During a four-day period after methyl mercury administration, the caecum-resected mice excreted less inorganic mercury in the faeces than did sham-operated control mice (3.4% and 11.5% of the administered dose, respectively). Furthermore, the amount of total mercury excreted in the faeces was also smaller in the caecum-resected mice than in the control mice (9.3% and 19.3%, respectively). These data indicate that the caecum is important in the decomposition and faecal excretion of methyl mercury in mice.     

Sex and age differences in mercury distribution and excretion in methylmercury-administered mice

Sex differences in mercury distribution and excretion after single administration of methylmercury chloride (MMC, 5 mg/kg) were studied in mice. A sex difference in urinary mercury excretion was found in sexually mature mice (age of 7 wk) of C57BL/6N and BALB/cA strains. Males showed higher mercury levels in urine than females, though no significant difference was found in fecal mercury levels 24 h post exposure to MMC. The higher urinary excretion rates in males accounted for significant lowering of mercury levels in the brain, liver, and blood, but not in the kidney, which showed higher values. At 5 min, however, these sex difference was found only in the kidney, showing higher levels in males. Changes in mercury distribution with time were studied in C57BL/6N mice. The brain mercury increased in both sexes up to 3 d, and decreased only in males on d 5. Liver and blood mercury decreased with time in both sexes, and these were constantly higher in females than in males. Renal mercury in males decreased to similar levels to females on d 3. The sex differences at various ages were studied with C57BL/6N mice 24 h after dosing. Two-week-old mice, the youngest in this study, did not show significant sex difference in the mercury distribution and excretion, and their urinary mercury levels were much lower as compared to the older mice. Then, urinary mercury excretion in both sexes increased at 4 wk of age and then decreased at 45 wk of age. At 4, 7, 10, and 45 wk of age, males showed higher urinary mercury levels than females. These studies demonstrated sex and age differences in the mercury distribution and urinary excretion after methylmercury administration in mice. From these findings, it has been suggested that urinary mercury excretion may be related to sex hormones, especially androgens.     

Methyl Mercury Decomposition in Mice Treated with Antibiotics

Abstract: The role of intestinal flora in the decomposition and faecal excretion of methyl mercury was studied in mice treated with antibiotics. The antibiotics, neomycin sulfate and chloramphenicol, were given to mice in drinking water for six days before intraperitoneal administration of methyl mercuric chloride (MMC), and intestinal microorganisms were thereby reduced. Inorganic and organic mercury were determined separately for faeces, intestinal contents and organs. On the fourth day after the mercury administration, the percentage ratios of inorganic mercury to total mercury in the contents of the caecum and large intestine were less in the mice treated with antibiotics, at 37% and 39%, respectively, than in the control mice (66% and 65%, respectively). Administration of the antibiotics reduced the excretion of inorganic mercury in the faeces to 26% of that of control mice and also reduced the excretion of total mercury to 60%. Reduction of intestinal microorganisms by the antibiotics was assumed to have caused the reduced decomposition of methyl mercury in the caecal contents and the reduced excretion of total mercury in the faeces.     

Comparison of the effect of N-(2,3-dimercaptopropyl) phthalamidic acid, dl-penicillamine,and dimercaprol on the excretion of tissue retention of mercury in mice

The effect of N-(2,3-dimercaptopropyl) phthalamidic acid (DMPA) on the elimination and tissue retention of mercury was investigated on male ddY mice and was compared with those of dimercaprol (BAL) and dl-penicillamine (dl-p). When 75 mg/kg (about a quarter of an LD50) of DMPA and HgCl₂ (0.5 mg Hg/kg) were injected subcutaneously at almost the same time for 5 days, a decrease of the mercury concentration in vital organs and blood and an increase in urinary and fecal elimination of mercury were noted. These effects were greater than those caused by BAL (25 mg/kg) and dl-p (50 mg/kg) injections. DMPA injected after the discontinuation of HgCl₂ dramatically increased the fecal excretion of mercury and inhibited its retention in tissues more effectively than did BAL and dl-p. Approximately the same results were obtained in an experiment using equimolar doses (55 mg/kg for DMPA, 25 mg/kg for BAL, or 30 mg/kg for dl-p) of these compounds. The mechanism involved in the action of DMPA on fecal excretion of mercury was also investigated. DMPA (75 mg/kg) and BAL (25 mg/kg) enhanced the bile flow rate and mercury excretion into bile, the effect of DMPA on the latter being 15% of the body burden and that of BAL, 5.4%, dl-p (50 mg/kg) had no appreciable effect on this. The thiol compounds did not immediately induce the absorption of mercury in bile from the small intestine, but 2 hr later about 8% of the mercury was absorbed in the DMPA group only. The compounds increased slightly the intestinal transit of mercury. An increase of mercury in feces after the injection of DMPA was thus concluded to be due to an increase in biliary excretion.     

Effects of age and sex on retention of mercury by methyl mercury-treated rats

Male and female Long Evans rats 7, 15, 20, 24, or 56 days old received a single subcutaneous injection of 1 μmol of methyl mercury-203/kg and the whole body retention of radiomercury was determined for up to 139 days thereafter. For rats dosed at 7 or 15 days of age, whole body clearance of mercury was extremely slow until animals reached 17 to 18 days of age. Subsequent excretion was monoexponential in the 7-day-old group and biexponential in the 15-day-old group. For rats dosed at 20, 24, or 56 days of age, onset of excretion was immediate and the pattern of clearance was biexponential. In rats dosed at 56 days of age, the retention of mercury by the average male and average female was significantly different (p = 0.001). No sexual difference in the estimate of whole body retention of mercury was seen in the other age groups. The presence of an interval of very slow excretion of mercury in young rats and the subsequent slower excretion of mercury in these animals than in rats dosed with methyl mercury later in life suggest that increased hazards of methyl mercury exposure in early life may be related to increased retention of the organomercurial or inorganic Hg.     

The Mechanism of Biliary Excretion of Methyl Mercury: Studies with Methylthiols

Abstract: The S-methylated derivatives of N-acetylpenicillamine, thiola and cysteine as well as methyl iodide decreased biliary excretion of methyl mercury markedly. Excretion of sulfhydryl in bile was not influenced by S-methyl-cysteine, S-methylthiola, S-methyl-N-acetylpenicillamine or a low dose of methyliodide (0.5 mmol/kg body weight). This seems to indicate that coupling of methyl mercury to glutathione in the liver before biliary excretion is a glutathione S-transferase dependent reaction. It also indicates that the methylthiols tested, or metabolites of these compounds are likely to be inhibitors of S-transferase. The effect of S-methylcysteine and low doses of methyl iodide probably reflects glutathione S-transferase inhibition as both compounds are metabolized to the S-transferase inhibitor S-methylglutathione in the liver. A higher dose of methyl iodide (1 mmol/kg body weight) seems to deplete the liver of reduced glutathione through S-methylation as illustrated by decreased biliary excretion of sulfhydryl. S-methylthiola and S-methyl-N-acetylpenicillamine are metabolized in the liver to unknown components which are excreted in bile. Whether S-methylthiola and S-methyl-N-acetylpenicillamine are inhibitors of S-transferase themselves or cause inhibition through metabolites cannot be stated from the present investigation.     

Treatment of methyl mercury poisoning in mice with 2,3-dimercaptosuccinic acid and other complexing thiols

Treatment with 2,3-dimercaptosuccinic acid was more effective than N-acetyl-DL-penicillamine and monomercaptosuccinic acid in mobilizing mercury from mice after the injection of methyl mercuric chloride. Dimercaptosuccinic acid treatment started 4 days after the mercury injection and given for 8 days at a dose of 1 mmol SH/kg per day removed more than 2/3 of the mercury in the brain, while acetylpenicillamine and mercaptosuccinate correspondingly removed less than 1/2 of the brain deposits. Neither treatment with 2,3-dimercaptorropano-1-sulphonate nor with a new thiolated resin, mercaptostarch, mobilized significant amounts of mercury from the brain. Since the toxicity of dimercaptosuccinate seems to be almost as low as that of D-penicillamine this dithiol may provide a potentially useful agent in clinical poisoning due to methyl mercury.     

Treatment of mercuric chloride poisoning with dimercaptosuccinic acid and diuretics: preliminary studies

The distribution and excretion of mercury were studied in mice given a single injection of HgCl2 with or without chelation treatment. DMS (2,3-dimercaptosuccinic acid) given intravenously (0.5 mmol SH/kg) to mice 24 h after the mercury injection reduced the kidney Hg level significantly, while NAPA (N-acetyl-DL-penicillamine) and BAL (2,3-dimercaptopropanol) did not. The effectivity of DMS to remove Hg from kidneys was comparable to that of BAL-sulph (2,3-dimercaptopropane-1-sulfonate), irrespective of whether these chelating agents were given orally or intravenously. Immediate chelation treatment with DMS or mercaptodextran reduced the renal Hg level to about 50% of control levels, as measured 3 d after the treatment. Combination of DMS with immediate intraperitoneal treatment with spironolactone was even more effective in reducing the renal levels, and acted both by increasing the fecal and urinary excretion. The DMS treatment, as well as DMS + spironolactone in combination, could protect against kidney damage following injection of 30 mumol HgCl2/kg. Such treatment was essentially nontoxic.     

Protective Effects of Ca2+ Channel Blockers against Methyl Mercury Toxicity

Abstract: The protective effects of Ca²⁺ channel blockers against the toxicity of methyl mercury were examined by both in vivo and in vitro experiments. In the in vivo study we first examined the effects of the Ca²⁺ channel blockers (20 mg/ kg/day), flunarizine, nifedipine, nicardipine, and verapamil against the toxic level of methyl mercury treatment (5 mg/kg/ day of methyl mercuric chloride for 12 consecutive days). However, there was a difference in potency of the effects among the reagents. All the Ca²⁺ channel blockers prevented a decrease in body weight and/or the appearance of the symptoms of neurological disorders in the rats treated with methyl mercury. In the next experiment, we examined flunarizine at different levels of supplementation (1,25 and 50 mg/kg/day). Flunarizine in a dose-dependent manner prevented a decrease in body weight, appearance of the symptoms of neurological disorder and mortality in the rats treated with methyl mercury. Flunarizine treatment (25 mg/kg/day) for the first 5 days did not affect mercury distribution among the tissues, suggesting that the mechanism of protection against methyl mercury-induced toxicity may be attributed to its own pharmacological effect. In the in vitro study we examined the effect of flunarizine (0, 0.5, 5 and 50 μM) using primary cultures of cerebellar granular cells in 96-well culture plates. Viable cell numbers were estimated 1 and 3 days after treatment with methyl mercury. The estimated 50% lethal concentration (LC50) of methyl mercury was higher in plates treated with 5 and 50 uM of flunarizine both on days 1 and 3, indicating that flunarizine protected the primary cultured cerebellar granular cells against the toxicity of methyl mercury. As such, Ca²⁺ channel blockers protected against the toxicity of methyl mercury both in vivo and in vitro, suggesting that Ca²⁺ plays an important role in the mechanisms of methyl mercury toxicity.     

Thimerosal distribution and metabolism in neonatal mice: comparison with methyl mercury

Thimerosal, which releases the ethyl mercury radical as the active species, has been used as a preservative in many currently marketed vaccines throughout the world. Because of concerns that its toxicity could be similar to that of methyl mercury, it is no longer incorporated in many vaccines in the United States. There are reasons to believe, however, that the disposition and toxicity of ethyl mercury compounds, including thimerosal, may differ substantially from those of the methyl form. The current study sought to compare, in neonatal mice, the tissue concentrations, disposition and metabolism of thimerosal with that of methyl mercury. ICR mice were given single intramuscular injections of thimerosal or methyl mercury (1.4 mg Hg kg(-1)) on postnatal day 10 (PND 10). Tissue samples were collected daily on PND 11-14. Most analysed tissues demonstrated different patterns of tissue distribution and a different rate of mercury decomposition. The mean organic mercury in the brain and kidneys was significantly lower in mice treated with thimerosal than in the methyl mercury-treated group. In the brain, thimerosal-exposed mice showed a steady decrease of organic mercury levels following the initial peak, whereas in the methyl mercury-exposed mice, concentrations peaked on day 2 after exposure. In the kidneys, thimerosal-exposed mice retained significantly higher inorganic mercury levels than methyl mercury-treated mice. In the liver both organic and inorganic mercury concentrations were significantly higher in thimerosal-exposed mice than in the methyl mercury group. Ethyl mercury was incorporated into growing hair in a similar manner to methyl mercury. The data showing significant kinetic differences in tissue distribution and metabolism of mercury species challenge the assumption that ethyl mercury is toxicologically identical to methyl mercury.     

The effects of dimercaptosuccinic acid on the excretion and distribution of mercury in rats and mice treated with mercuric chloride and methylmercury chloride.

1 All five rats in a group survived if dimercaptosuccinic acid (DMSA), a water soluble derivative of 2,3-dimercaptopropanol (BAL), was given in doses of 10-40 mg/kg intraperitoneally 30 min, 4 and 24 h after administration of 2.4 mg/kg Hg as HgCl2, whereas three out of a group of five died if DMSA was not given. DMSA 20 mg/kg increased urinary excretion and decreased the body burden significantly more than 10 mg/kg DMSA, but further doubling of the dose had only marginal effects. 2 DMSA was able to reduce body burden and increase urinary excretion of Hg when intraperitoneal treatment started eight days after the subcutaneous administration of HgCl2. 3 DMSA was effective in decreasing body burden and the brain concentration of Hg in rats dosed orally with methylmercury (MeHgCl) when intraperitoneal treatment started with 40 mg/kg DMSA 24 h after Hg. Increase in the urinary excretion of mercury was responsible for the decrease in body burden. 4 DMSA was effective when given in the drinking water of rats or mice both against inorganic Hg and MeHgCl. In mice treated intraperitoneally with MeHgCl, DMSA 19.5 mug/ml in the drinking water caused a significant decrease in the body burden and increase in the excretion of Hg. 5 DMSA was about four times more efficient than D-penicillamine in decreasing the body burden of Hg. As their toxicity is in the same range, the higher efficiency of DMSA offers a larger margin of safety for the mobilization of Hg.     

Excretion of Methyl Mercury in Rat Bile: The Effect of Thioctic Acid,Thionalide, Hexadecyl- and Octadecylmercaptoacetate

Abstract: Thioctic acid markedly increases the sulfhydryl and sulphide content of bile. This probably reflects the reduction of thioctic acid in the liver, followed by biliary excretion of a reduced derivative. The total biliary excretion of methyl mercury was not increased. Thionalide markedly inhibits biliary excretion of methyl mercury. Simultaneously, the sulfhydryl and sulphide content of bile decreases. This is probably caused by the conjugation of thionalide to glutathione in the liver, thereby blocking the biliary excretion of methyl mercury. Hexadecylmercaptoacetate increases the biliary content of methyl mercury moderately after a temporary decrease, whereas biliary sulfhydryl and sulphide concentrations were unchanged. Octadecylmercaptoacetate does not change the biliary content of methyl mercury, sulfhydryl and sulphides significantly. Smaller parts of hexadecylmercaptoacetate, octadecylmercaptoacetate and thionalide seemed to be excreted as such in bile. These results indicate that methyl mercury cannot be transported from liver to bile as complexed to the sulphides thioctic acid, thionalide, hexa- and octadecylmercaptoacetate.