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.     

Methyl mercury: acute toxicity, tissue distribution and decay profiles in the guinea pig

Acute toxicity studies with methyl mercuric chloride showed that the guinea pig was quite susceptible to methyl mercury intoxication. LD50 values were 5.5 mg Hg/kg ip and 16.5 mg Hg/kg po. One to 2 weeks after dosing, several animals began to display signs of neurotoxicity.Tissue distribution and pharmacodynamic studies with radiolabeled methyl mercuric chloride ([²⁰³Hg]CH₃HgCl) at 1 and 10 mg Hg/kg revealed that while most tissues decreased in mercury concentration from day 1 to day 7, cerebrum, cerebellum and muscle showed a delayed uptake of the alkyl mercurial. In CNS tissue the concentration of mercury decreased in the order cerebrum > cerebellum > spinal cord. Kidney and liver consistently contained the highest levels of mercury, and plasma the lowest, during the 49-day sampling period. One week after dosing the blood: brain ratios were less than 1. The tissue concentration of mercury was generally directly proportional to the dose administered; however, mercury levels in the gall bladder were significantly higher than anticipated on 5 of the 7 sacrifice days.Most of the tissues displayed a biphasic decay profile with a half-life of 2–3 days for the initial rapid phase of decline. This initial phase was followed by a slower tissue excretion rate for which the mean half-life for mercury was 15 ± 0.9 days and 15 ± 0.8 days for the low and high dose, respectively. The similarity of these values again indicates no dose-related effects.     

Distribution of mercury in rabbits subchronically exposed to low levels of radiolabeled methyl mercury

The metabolism of methyl mercury (MeHg) has been studied in rabbits administered 203Hg-labeled methyl mercuric chloride, 0.125 mumol/kg body weight, twice a week for 9 weeks, by intravenous injection. Twelve weeks after cessation of treatment, about 54% of the administered dose had been excreted in faeces and 5% in urine. After one week, the highest concentration of 203Hg was found in fur (8.6 nmol Hg/g). Substantially lower concentrations were found in kidney (2.5 nmol/g), liver (0.9 nmol/g), brain (0.4 nmol/g), muscle (0.3 nmol/g) and blood (0.1 nmol/g). The rate of elimination of 203Hg from brain, muscle and blood was faster (t1/2 about 12 days) than that from kidney and liver (t1/2 about 28 days). The relative amount of inorganic Hg in kidney and liver increased with time after cessation of treatment. The highest fractions were 85 and 70%, respectively. In brain, no significant demethylation of MeHg could be detected.     

Toxicokinetics of methyl mercury in pigs

Toxicokinetics of methyl mercury were studied in pigs after intravenous (i.v.) administration of the compound. The distribution of methyl mercury was slow taking 3–4 days to be completed. Blood elimination half-life was found to be 25 days. The apparent volume of distribution was 9.8 l/kg indicating pronounced tissue accumulation of methyl mercury. Highest mercury levels were found in kidney and liver, with lower contents in muscle and brain and very little in adipose tissue. The results indicate that from organs like liver and kidney methyl mercury is eliminated much more slowly than from the blood. Over a period of 15 days 16% of the dose administered was excreted with faeces and 0.9% in the urine.     

Pharmacodynamics of methyl mercury in the rainbow trout (Salmo gairdneri): tissue uptake, distribution and excretion

The tissue distribution, rate of uptake and concentration of ²⁰³Hg-labeled methylmercury was investigated in 20 different tissues/organs over a period of 100 days following a single intragastric dose of 0.5 mg Hg/kg body weight. Mercury content was analyzed by gamma scintillation spectrometry. After 1 hr, mercury concentration factors >0.1 were detected in the blood, heart, liver, spleen and kidney (a concentration factor (CF) of 1.0 equals mercury concentration in dose). Highest mercury concentrations (CF > 7.0) were observed in the blood (at 7 days) and spleen (at 14 days). After 100 days, the CF of the blood was >2.0 and the CF values of the spleen, kidney and liver were >1.0. Maximum CF values were reached in the skeletal muscle, brain and lens after 34, 56 and >90 days, respectively. Maximum values were reached in most other tissues/organs at approximately 7 days. Skeletal muscle appeared to function as a reservoir for methyl mercury and accumulated 50% of the dose from 34 to 100 days post administration. Methyl mercury accumulation in the brain was limited to 0.1% of the dose. The rate of mercury excretion appeared to be biphasic as a result of a slow elimination from the skeletal muscle relative to the other tissues/organs. Employing both the slow and fast rate, the half-retention time for methyl mercury in rainbow trout was estimated to be >200 days.     

Methyl mercury and selenium interaction in relation to mouse kidney gamma-glutamyltranspeptidase, ultrastructure, and function

The effects of methyl mercury (CH3Hg) and selenium (Se) on renal ultrastructure were investigated and correlated to changes in renal gamma-glutamyl transpeptidase (gamma-GTPase) activity, mercury (Hg) accumulation, and renal function (serum creatinine and urea nitrogen). Three experimental protocols were used to investigate CH3Hg and Se interactions of both Se-sufficient and Se-deficient mice involving ip injection of the following administered alone or in combination: CH3Hg (4.0 mg/kg) and Se (0.16 mg/kg) daily for 7 days, CH3Hg (1.0 mg/kg) and Se (0.08 mg/kg) daily for 20 days, and a single acute dose of CH3Hg (8.0 mg/kg). Acivicin (12 to 50 mg/kg), an antitumor glutamine antagonist, was also used as a highly effective specific inhibitor of the gamma-GTPase. Our results show that CH3Hg administered to Se-deficient mice for 7 or 20 days resulted in significant (p less than or equal to 0.05) but only moderate inhibition (20%) of gamma-GTPase activity and extensive renal ultrastructural damage. Acivicin-treated mice had significant inhibition of gamma-GTPase activity (80%) following a single injection while ultrastructural damage was substantial only after several days of administration. These results may indicate different modes of action of acivicin and CH3Hg. Acivicin inhibited gamma-GTPase prior to renal damage while CH3Hg produced greater pathological effects with only moderate gamma-GTPase inhibition. Renal damage from acute and chronic CH3Hg toxicity occurred after distinct neurological signs were present. Selenium administered to Se-deficient mice ameliorated both the neurotoxic effects and nephrotoxic action of CH3Hg. While Se and CH3Hg treatments caused some of the same ultrastructural pathology as the treatment with CH3Hg alone (cytoplasmic vacuolation, increased lysosomal profile, mitochondrial swelling, and extrusion of cellular masses into the tubular lumen), degeneration was not as extensive. Although the total doses administered during both the 7- and the 20-day studies were similar, mice from the chronic 20-day study showed greater ultrastructural pathological effects from CH3Hg. The primary effects of CH3Hg appeared to be on the lysosomal system, while acivicin exerted its effects on the mitochondrial and endoplasmic reticulum systems. The accumulation studies on Hg suggest that dietary Se may have only an initial protective effect against Hg accumulation in the kidney while injected Se offers longer protection.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of Repeated Dosing of Methyl Mercury on in Vivo Protein Synthesis in Isolated Neurones

Abstract: Wistar rats were given orally methyl mercury in daily doses for up to 45 days. Animals receiving 5 mg methyl mercury/kg developed weight loss after 20 doses. The neuronal in vivo protein synthesis was affected in both groups given 1 and 5 mg methyl mercury/kg. Weight loss, early toxic signs and a decreased protein synthesis all seem to occur at a cerebellar mercury level between 3–6 μg Hg/g.     

Correlation of neurochemical and behavioral effects of triethyl lead chloride in rats

Adult male Fischer-344 rats were dosed sc with 1 or 2.5 mg/kg of triethyl lead chloride (TEL) for 5 consecutive days. One week after the last dose, TEL-exposed rats had decreased Met-enkephalin in the hypothalamus, septum, and frontal cortex, while substance P was decreased in the hippocampus and frontal cortex. Dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) in the caudate nucleus were not altered by TEL nor were serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the caudate nucleus, hypothalamus, hippocampus, or frontal cortex. In a second experiment, rats were dosed with 1.75 mg/kg sc for 5 days. Subsequent assay of brain tissue indicated that TEL decreased met-enkephalin levels in the septum of rats one and seven days after cessation of dosing; effects on substance P were not observed. TEL-induced decreases in Met-enkephalin in the septum were temporally associated with increased hot plate latencies. One day after cessation of dosing with TEL, concentration of 5-HIAA in the caudate nucleus, hippocampus, frontal cortex, and brain stem, and 5-HT in the hippocampus and brain stem were increased. Biogenic amine concentrations were not affected in any other region or at any other time postdosing. A third experiment indicated that TEL-induced analgesia could be attenuated by 10 mg/kg chlordiazepoxide or 10 mg/kg of naloxone. The present results suggest that TEL-induced analgesia may be due to alterations in emotionality or reactivity to noxious stimuli, which may be associated with the alteration in delta opiate mechanism in the limbic system, such as the change of septal enkephalin neuronal activities.     

The kinetics of methylmercury administered repeatedly to rats

Female rats (65–75 days old) were given orally 0.84 or 3.36 mg Hg/kg as methylmercury chloride (MeHgCl) 5 times a week for 13 and 3 weeks, respectively. The proportion of inorganic to total mercury remained as low as 6% in whole animal though it increased to above 40% in the kidneys.Differences in organ half times and the negative correlation with time for blood to liver, brain and kidney mercury ratios indicated more than one compartment for MeHg⁺. Brain had 26 days half time with a 32% final equilibrium concentration in relation to the body concentrations. Brain concentrations of mercury reported on rats dosed repeatedly with MeHg⁺ agreed with these values which justifies their use when experiments are planned to give a certain brain MeHg⁺ concentration.Half time for the whole body was 34 days but pathological changes — weight loss, tubular damage, slow gastrointestinal passage — disturbed the accumulation curves in the higher dose group. Blood to kidney ratio and uptake of MeHg⁺ by kidneys also changed significantly.     

Combined effect of sodium maleate and some thiol compounds on mercury excretion and redistribution in rats

1. (+)-Penicillamine in a dose of 193 μmoles/kg given subcutaneously twice a day on the sixth and seventh days after the administration of 100 μg mercury increased the urinary excretion of rats more than the equimolar dose of N-acetyl-(+)-penicillamine but less than 2,3-dimercaptopropanol 48.3 μmoles/kg.

2. Sodium maleate in a dose of 156 μmoles/kg given on the sixth and seventh days after the mercury did not influence mercury excretion or redistribution. Sodium maleate in the same dose increased considerably the effect of (+)-penicillamine on the urinary excretion and redistribution of mercury. It increased the effect of N-acetyl-(+)-penicillamine only slightly. There was a tendency to decrease the effect of 2,3-dimercaptopropanol.

3. All the complexing agents decreased the kidney content of mercury and increased the liver and blood concentration of mercury. These changes were highest with 2,3-dimercaptopropanol. The combination of sodium maleate with (+)-pencillamine caused higher mercury excretion and lower kidney content but a smaller increase in the liver and blood mercury contents than 2,3-dimercaptopropanol.

     

Altered intrarenal accumulation of mercury in uninephrectomized rats treated with methylmercury chloride.

We tested the hypothesis that the intrarenal accumulation of mercury in rats treated with methylmercury is altered significantly as a result of unilateral nephrectomy and compensatory renal growth. Renal accumulation of mercury was evaluated by radioisotopic techniques in both uninephrectomized (NPX) and sham-operated (SO) rats 1, 2, and 7 days after the animals received a nonnephrotoxic intravenous dose of methylmercury chloride (5 mg/kg Hg). At all times studied after the injection of the dose of methylmercury, the renal accumulation of mercury (on a per gram kidney basis) was significantly greater in the NPX rats than that in the SO rats. The increased accumulation was due to a specific increase in the accumulation of mercury in the outer stripe of the outer medulla. Renal cortical accumulation of mercury was similar in both the NPX and SO rats. The percentage of the administered dose of mercury that was present in the total renal mass of the NPX and SO rats ranged between 5 and 15, depending on the day that the renal accumulation was studied. Approximately 40-50% of the total renal burden of mercury in both the NPX and SO rats was in the inorganic form. However, only less than 1% of the mercury in blood was in the inorganic form at the three times accumulation was studied. Very little mercury was excreted in the urine by either the NPX or SO rats. Only about 2 to 3% of the administered dose of mercury was excreted in the urine in 7 days. By contrast, the cumulative fecal excretion of mercury over 7 days was substantial in the NPX and SO rats, and significantly more mercury was excreted in the feces by the NPX rats (about 19% of the dose) than by that in the SO rats (about 16% of the dose). In conclusion, our findings indicate that unilateral nephrectomy and compensatory renal growth cause a significant increase in the accumulation of mercury in the renal outer stripe of the outer medulla in rats exposed to methylmercury. In addition, the findings indicate that the fecal excretion of mercury is also significantly increased.     

Effects of 2,3-dimercapto-1-propanesulfonic acid (DMPS) on tissue and urine mercury levels following prolonged methylmercury exposure in rats.

Methylmercury, a potent neurotoxicant, accumulates in the brain as well as the kidney during chronic exposure. We evaluated the capacity of 2,3-dimercapto-1-propanesulfonic acid (DMPS), a tissue-permeable metal chelator, to reduce brain, kidney, and blood Hg levels and to promote Hg elimination in urine following exposure of F-344 rats to methylmercury hydroxide (MMH) (10 ppm) in drinking water for up to 9 weeks. Inorganic (Hg2+) and organic (CH3Hg+) mercury species in urine and tissues were assayed by cold vapor atomic fluorescence spectroscopy (CVAFS). Following MMH treatment for 9 weeks, Hg2+ and CH3Hg+ concentrations were 0.28 and 4.80 microg/g in the brain and 51.5 and 42.2 microg/g in the kidney, respectively. Twenty-four hours after ip administration of a single DMPS injection (100 mg/kg), kidney Hg2+ and CH3Hg+ declined 38% and 59%, whereas brain mercury levels were slightly increased, attributable entirely to the CH3Hg+ fraction. Concomitantly, Hg2+ and CH3Hg+ in urine increased by 7.2- and 28.3-fold, respectively, compared with prechelation values. A higher dose of DMPS (200 mg/kg) was no more effective than 100 mg/kg in promoting mercury excretion. In contrast, consecutive DMPS injections (100 mg/kg) given at 72-h intervals significantly decreased total mercury concentrations in kidney, brain, and blood. However, the decrease in brain and blood mercury content was restricted entirely to the CH3Hg+ fraction, consistent with the slow dealkylation rate of MMH in these tissues. Mass balance calculations showed that the total amount of mercury excreted in the urine following successive DMPS injections corresponds quantitatively to the total amount of mercury removed from the kidney, brain, and blood of MMH-exposed rats. These findings confirm the efficacy of consecutive DMPS treatments in decreasing mercury concentrations in target tissue and in reducing overall mercury body burden. They demonstrate further that the capacity of DMPS to deplete tissue Hg2+ is highly tissue-specific and reflects the relative capacity of the tissue for methylmercury dealkylation. In light of this observation, the inability of DMPS to reduce Hg2+ levels in brain or blood may explain the inefficacy of DMPS and similar chelating agents in the remediation of neurotoxicity associated with prolonged MMH exposure.     

Time-dependent tissue/organ uptake and distribution of 203Hg in mice exposed to multiple sublethal doses of methyl mercury.

Swiss-Webster mice were injected intraperitoneally with one to ten doses (2.5 mg Hg/kg) of ²⁰³Hg-labeled methyl mercury. Doses were administered at 72-hr intervals. Maximal tissue/organ Hg uptake usually occurred 72 hr postinjection and was monitored at 3 and 6 days by gamma scintillation spectrometry. Most tissues/organs required five to six doses to attain maximal Hg concentrations (the carcass required seven doses; hair and fat, eight doses; lens, nine doses). Data for hair were highly variable. Except for hair (which required seven to eight doses), maximal tissue/organ concentration factors (CF) were reached 72 hr after the first dose. Kidney, liver, and hair attained CF values > 1. Except for hair, all CF values decreased with increasing dose number. Initial rates of decrease were much greater for kidney, blood, spleen, muscle, and liver than lens, brain, and fat. Only hair exhibited a significantly higher Hg concentration at 6 days after each dose than at 3 days. With increasing dose number, blood Hg; tissue/organ Hg ratios remained relatively constant for liver, kidney, spleen, and muscle; decreased for lens and brain; and decreased for hair and fat after an initial increase.     

Effects of developmental exposure to methyl mercury on spatial and temporal visual function in monkeys

Detailed characterization of several aspects of visual function was made in two groups of monkeys exposed developmentally to methyl mercury. One group of monkeys (Macaca fascicularis) was dosed from birth onward with 50 micrograms/kg/day of mercury as methyl mercury. Another group was exposed in utero by dosing the mother with 10, 25, or 50 micrograms/kg/day of mercury as methyl mercury, and postnatally until 4.0-4.5 years of age with the same dose the mother had received. Spatial and temporal visual function was tested in both groups. Spatial visual deficits observed in the group dosed beginning postnatally were reported previously (Rice and Gilbert, 1982, Science, 216, 759-761). Monkeys exposed in utero plus postnatally exhibited impaired high- and low-luminance spatial vision. They also exhibited deficits in low-frequency high-luminance temporal vision, while low-luminance temporal vision was superior to that of control monkeys. Monkeys in which exposure began at birth displayed superior low-luminance temporal vision, while high-luminance temporal vision was not impaired. These effects were observed in the absence of constriction of visual fields. These data suggest that the pattern of visual deficits produced by developmental exposure to methyl mercury may be different from that in the adult, and that the developing visual system may be able to remodel as a result of early insult by a neurotoxic agent.     

Augmentation of sulfate ion absorption from the rat lung by heavy metals.

In rats injected ip with 500 mg of cyclotrimethylenetrinitramine (RDX)/kg, the respective mean times to first seizure and to death were 23.8 and 171.0 min, and the mean plasma concentrations of RDX at seizure and death were 5.2 and 13.8 μg/ml. Following 100 mg/kg po, the plasma concentration was 2.1 μg/ml at 4 hr and 3.0 μg/ml at 24 hr, while the urine concentration was 5.5 μg/ml at 4 hr and 6.9 μg/ml at 24 hr. In the 6 days following 50 mg/kg po, 0.7% was excreted as RDX in the feces and 2.4% in the urine. Irrespective of dosage or route of administration, the concentration of RDX was greatest in kidney, most variable in liver, and did not accumulate in the brain. Twenty-four hours after po dosing with 50 mg of [¹⁴C]RDX/kg, the liver and urine contained large amounts of RDX metabolites, and, after the first 4 days, 90% of the total radioactivity was recovered: 34% in the urine, 43% as ¹⁴CO₂, 3% in the feces, and 10% in the carcass. In miniature swine dosed with 100 mg/kg po, the plasma concentration was 1.6 μg/ml at 2 hr and 4.7 μg/ml at 24 hr, while the urinary concentration was 2.0 μg/ml at 2 hr and 3.6 μg/ml at 24 hr. At 24 hr, the concentrations of RDX in brain, heart, liver, kidney cortex, kidney medulla, and fat were between 4.4 and 9.1 μg/g. Convulsions in pigs occurred 12–24 hr after dosing with RDX.     

Biliary excretion of mercury compounds.

The disappearance of ²⁰³Hg from the plasma of rats and its excretion into bile was quantitated for 2 hr after the iv administration of 0.03, 0.1, 0.3, 1.0, and 3.0 mg Hg/kg as ²⁰³mercuric chloride. The concentration of ²⁰³Hg in the bile was usually about 0.66 that in the plasma. The concentration of ²⁰³Hg in the liver was 1.8–3.4 times higher than that in the plasma, and the bile concentration was about three times lower than that in the plasma. Methyl mercuric chloride was given to rats at dosages of 0.1, 0.3, 1.0, and 3.0 mg Hg/kg, iv. The concentration of ²⁰³Hg in bile averaged about nine times higher than that in the plasma, the liver concentration was about 25-fold higher than that in the plasma and the bile concentration about 0.33 that in the liver. Thus the radioactivity associated with either mercuric chloride or methyl mercury were not highly concentrated in bile as are some other heavy metals. Over a 2-hr period, regardless of the dose or the form of Hg administered, less than 0.5% of the dose was excreted into the bile. The effect of 4 days pretreatment with phenobarbital, spironolactone, pregnenolone-16-carbonitrile (PCN), and 3-methylcholanthrene on the biliary excretion of mercuric chloride and methyl mercury was also measured. PCN was the most effective, doubling the amount of ²⁰³Hg excreted into the bile.     

Effects of coadministered low-molecular-weight thiol compounds on short-term distribution of methyl mercury in the rat

Following iv administration to the rat, methyl mercury was rapidly deposited in the liver, kidneys, and cerebrum. Methyl mercury concentrations in cerebrum 5 min after injection were about equal to the levels attained at 60 min post-treatment. At 5 min after dosing, concentrations of methyl mercury in plasma and tissues were directly proportional to the dose level of methyl mercury. Coadministration of equimolar amounts of l-cysteine increased short-term accumulation of methyl mercury in liver, kidneys, and cerebrum while reducing the levels of methyl mercury in plasma from those found after administration of methyl mercury alone. Equimolar doses of d-cysteine or d-penicillamine lowered plasma methyl mercury levels below those produced by injection of methyl mercury alone, but coadministered N-acetyl-l-cysteine or l-penicillamine did not. Each of these low-molecular-weight thiol compounds given in combination with methyl mercury increased deposition of methyl mercury in liver and kidneys. In addition, l-penicillamine also increased accumulation of methyl mercury in the cerebrum. These results suggest a critical role of plasma methyl mercury levels in the control of short-term methyl mercury distribution. Modification of the distribution pattern by coadministered low-molecular-weight thiol compounds further suggests that methyl mercury-thiol complexes may play a role in the tissue deposition process.     

Methylmercury exposure, mercury levels in blood and hair, and health status in Swedes consuming contaminated fish

Levels of total mercury in blood cells ranging 8–390 ng/g (in one case 1100) were found in 162 Swedes who consumed fish containing 0.3–7 mg Hg/kg. Levels above 100 ng/g were seen only in subjects 40–80 years of age, levels above 200 ng/g only in persons who consumed fish containing about 1 mg Hg/kg or more. 20 subjects eating fish containing about 0.04 mg Hg/kg ranged 8–45 ng/g blood cells, and 22 subjects eating commercially available fish 3–57 ng/g. Long-term exposure to 4 μg Hg as methylmercury/kg body weight/day - as estimated from fish intake records - corresponded to a blood cell mercury level of about 300 ng/g. After the end of exposure, biologic half-time of mercury in blood cells ranged 58–87 days in 4 subjects, while the corresponding figure was 164 days in one individual. A screening for signs and symptoms of methylmercury poisoning in 86 of the exposed subjects revealed no clearcut case of poisoning. Some subjects of symptoms in a high-mercury (82–1100 ng/g blood cells) group as compared to a low-mercury (12–75 ng/g) group.     

Effects of ethanol on methyl mercury toxicity in rats

This study was designed to investigate the effect of different doses of ethanol on the morbidity, mortality, and distribution of mercury in the tissues of groups of rats treated orally once daily with methyl mercury chloride (MMC: 5 mg/kg . d) for 10 consecutive days. Ethanol potentiated the toxicity of methyl mercury in terms of neurological manifestations (hindleg crossings and abnormal gait) and mortality. The magnitude of effect depended on the concentration of ethanol administered. The concentration of mercury in the kidney and brain also increased with the dose of ethanol given. These findings indicate that epidemiologic studies designed to evaluate methyl mercury toxicity must take into account the multiple environmental burdens that can affect the population cumulatively and simultaneously.     

Gentamicin nephrotoxicity in cadmium, lead and mercury pretreated rats

The effect of a previous chronic exposure to cadmium, lead or inorganic mercury on the nephrotoxic potential of gentamicin was investigated in female Sprague-Dawley rats. A daily dose of 10 mg gentamicin/kg body weight/day was administered for 21 days to rats having a renal load of 168 micrograms Cd, 35 micrograms Pb or 129 micrograms Hg/g whole kidney. Urine analysis suggests an attenuation of the nephrotoxic potential of gentamicin while a microscopical examination of kidneys indicates a superimposition of the effects of the metals and the antibiotics. The only clear interaction observed consists in a reduction of gentamicin accumulation in the cortex of cadmium-treated animals. It is concluded that none of the metal pretreatments potentiates the nephrotoxic effects of gentamicin.