Archives of
Arch. Toxicol. 38, 201--207 (1977)
TOXICOLOGY 9 by Springer-Verlag 1977
The Effect of Selenium on the Brain Uptake of Methylmercury* L. Magos** and M. Webb MRC ToxicologyUnit, Medical Woodmansterne Road, Carshalton, Surrey, SM5 4EF, Great Britain
Abstract. Twenty-four h after the subcutaneous administration of 0.5 pxmoles selenite labelled with 755eto rats of 200 g body weight, the retention of selenium at the injection site was significantly increased by the presence of equimolar amounts of methylmercury in the injection solution. The retention of Me2~ was not affected by the presence of selenite. The most significant shift caused by interaction was a decrease in the blood content and an increase in the brain content of 2~ The brain content of 75Sewas also increased to a lesser extent. The shift in the distribution - which was the same whether the two metals were injected at the same site or separately -- continuously decreased from 6 - 4 8 h. The same interaction pattern was observed when methylmercury and selenite were administered by gastric gavage and differences in distribution increased when the dose was increased from 1.25 ~moles/kg to 2.5 ~moles/kg. The increase in the brain content of mercury caused by selenite was not restricted to simultaneous administration and occurred when selenite was given 2 - 7 days after methylmercury.
Key words: Methylmercury -- Selenium -- Brain - Blood - Interaction.
Introduction Selenium is able to decrease the toxicity of methylmercury in food (Ganther et al., 1972; Stoeswand et al., 1974; Stillings et al., 1974), although recently Ohi et al. (1976) observed that selenium in tuna fish was approximately half as efficient as selenite in the prevention of the neurological effects of methylmercury. The mechanism whereby selenium protects against the toxicity of methylmercury is not known, but it is certain that selenium in some form affects the organ distribution of methylmercury after various days of feeding schedule: selenium supplement seems to in* Supported partly by International Atomic Energy Agency Grant Number 1530/RB ** To whom offprint requests should be sent
202
L. Magos and M. Webb
crease the mercury concentration in the liver, spleen (Potter and Matrone, 1974) and in the brain (Ohi et al., 1975), although in the latter organ this effect can be absent (Ohi et al., 1976). This discrepancy might be explained by the difference in food intake or by the timing of the observation. Thus Iwata et al. (1973) observed that at 24 h after the last of 8 - 1 0 daily injections of methylmercury and selenium the brain accumulation of mercury was higher than in rats given methylmercury alone, whereas 6 days later it was lower. With the progress of intoxication, decreased food consumption with resultant drop in the intake of methylmercury and selenium, shift in metabolic balance, deficient kidney and liver functions are all likely to contribute to a change in the pattern of distribution and excretion of toxic metals. As it is difficult to interpret differences in distribution after multiple doses without knowledge of how the interacting metals behave after a single dose, a study has been made of the interaction between selenium (as Na2SeOa) and methylmercury (as CH3HgC1) by the single-dose experimental schedule that has been used in previous work (Magos and Webb, 1976a, b). Both compounds were injected subcutaneously alone, in combination as a single injection, or at different sites; organ contents and retention at the injection sites being determined usually after 24 h. Because of the importance of per os uptake, in some of the experiments the administration of selenite a n d / o r methylmercury was by gastric gavage, the selenite being given either together with methylmercury or 2, 3 or 7 days later.
Methods and Materials Injection Solutions. Cold stock solutions of MeHgC1 (K & K Laboratories Inc., Plainview,N.Y., USA)
or Na2SeO3 (BDH Chemicals Limited, Poole, England) were prepared in saline and were labelled with the corresponding isotope (Me2~ or Ne275SeO3)supplied by the Radiochemical Centre (Amersham, Bucks., England). Volumes of the subcutaneous injection solutions were 0.2 ml and they contained 0.5 ~moles MeHgC1 or Na2SeO3or both. Only one of them was labelled.For per os experiments solutions were prepared from the stock solutions and contained 1.25, 2.50 or 5.0 ~moles MeHgC1 in 5 ml saline with or without equivalent concentration of selenite, or 5.0 ~moles selenite alone if their administration was not simultaneous. They were injected by gastric gavage in a dose of 5 ml/kg. Animals in each experiment were injected either with 0.1 ~xCi2~ or 0.06 ~Ci 755e. Experimental Schedule. Male rats of Porton Wistar strain of approximately 200 g body weight were
used. In one group of experiments methylmercury chloride (MeHgC1) or Na2SeO3, or a mixture of the two, was injected subcutaneously into the right hind leg above the knee. In the second group of experiments, instead of injecting the mixture of MeHgC1 and Na2SeO3, the radioactively labelled compound was injected into the right hind leg, and the other under the neck. In the third group of experiments either MeHgC1 or Na2SeO3, or their mixture, was administeredby gastric gavage. Animals were killed by decapitation 6, 24 or 48 h after treatment. Blood from cervical vessels was collected in a beaker and was weighed. Liver, kidneys and brain (cerebrum, cerebellum and brain stem) were removed. Hind legs were removed by cutting through the hip joint. Radioactive Measurements. Live animals placed in a 14 x 6 x 6.5 cm plexiglass box were counted with
an efficiency of 9.6% for 2~ and 23.3% for 7~Se between two Nal crystal pairs (No. N656, Ekco Electronics Limited, Southend-on-Sea,Essex, England) facing each other. Faeces, urine, legs and organs were counted in a well-shaped NaI crystal (13 cm diameter, 11 cm depth), counting efficiencies being 43.0% for 2~ and 90.4% for 75Se.Injection standards in 1 ml acid permanganate solution were counted and metal contents in organs, excreta or in the whole animals were estimated after corrections for geometrical differences by relating their radio-activitiesto the standards. Radioactivity retained at
The Effect of Selenium on the Brain Uptake of Methylmercury
203
the injection site was determined from the difference between the injected and the control leg. Radioactivity in the total blood was calculated on the assumption that blood made up 7.0% of the body weight. Statistical Calculations. Statistical differences were estimated by the two tailed Student t test for
correlated groups for results presented in Tables 1, 2 and 3. The statistical differences in Figure 1 were calculated by the Student t test for independent means (two tailed test) and the selenium effect on the brain data and its dependence on time was calculated by the two-factor analysis of variance.
Results T a b l e 1 c o m p a r e s the retention, distribution and e x c r e t i o n o f 2~ and 7~Se after the s u b c u t a n e o u s a d m i n i s t r a t i o n o f Me2~ or Na275SeO3 with o r w i t h o u t the simult a n e o u s a d m i n i s t r a t i o n o f the o t h e r c o m p o u n d at the s a m e site. Selenite h a d no effect o n the r e t e n t i o n o f Me2~ at the injection site, d e c r e a s e d the c o n c e n t r a tion o f 2~ in b l o o d and kidneys and i n c r e a s e d it in the b r a i n a n d urine. M e t h y l m e r c u r y injected with selenite i n c r e a s e d the r e t e n t i o n o f 75Se at the injection site, a n d d e c r e a s e d the k i d n e y and liver c o n t e n t s o f 75Se. T h e b r a i n c o n c e n t r a t i o n o f 755e w a s i n c r e a s e d but n o t significantly. E x p e r i m e n t s in w h i c h the unlabelled c o m p o u n d w a s given at a different site s h o w e d a similar shift in the distribution o f 2~ or 7~Se with the e x c e p t i o n t h a t the retention o f 75Se w a s n o t affected b y M e H g C 1 . B r a i n c o n t e n t s w e r e n o t c o r r e c t e d to b l o o d value, but c o r r e c t i o n should increase a n d n o t d e c r e a s e the difference b e t w e e n the c o n t r o l a n d the selenite group. A s the w e i g h t o f b r a i n in 200 g rats is a p p r o x i m a t e l y 1.9 g, and the b l o o d c o n t e n t o f b r a i n in e x s a n g u i n a t e d animals is 19 m g / g ( W a n n a g , 1976), v a l u e s for b r a i n m e r c u r y p r e s e n t e d in T a b l e 1 should d e c r e a s e b y 0.11 for c o n t r o l s a n d 0.09 for selenite-treated rats. T h e corres p o n d i n g c o r r e c t i o n s for 755e are 0.013 and 0.012 respectively.
Table 1. The distribution of 2~ or 75Se 24 h after subcutaneous injection of 0.5 p,moles Me 2~ or Na2VSSeO3.The compounds were given either alone or (control) or in combination (experimental), when one component was not labelled Radioactivity in % of the dose (mean + SEM)
755e
Injection site Body burden Blood Brain Liver Kidneys Urinea Faecesa
2O3Hg
Control N = 10
Experimental N = 10
Control N=20
Experimental N=20
0.34+0.05 46.2 + 2.50 5.1 +0.24 0.10 _+0.01 11.5 _ 0.75 2.7 + 0.20 33.0 _+0.90 8.1 + 1.19
6.0 43.1 4.8 0.14 8.1 2.0 31.3 5.8
9.8 93.3 43.6 0.15 5.9 4.6 0.21 1.6
8.62-+ 1.11 95.6 _+0.95 36.0 + 1.21" 0.66 _+0.03* 5.21 _+0.2 2.7 -+ 0.09* 0.35 + 0.03* 1.6 + 0.21
_+0.53* + 1.11 +0.36 + 0.02 _+ 0.39* + 0.13" + 1.19 + 3.84
+0.28 + 2.56 + 1.56 + 0.02 _+0.23 + 0.45 _+0.02 +0.13
a N for excreta is half that for other samples, as one sample was collected from 2 animals * Significantly different from the control with the two tailed Student t test: p < 0.01
204
L. Magos and M. Webb
Fig. 1. The effect of interaction between Na2SeO 3 and MeHgC1 on their contents in blood (squares); brain (circles) and kidneys (triangles). Controls (broken line) were given only one metal subcutaneously in a dose of 0.5 ~moles per animal; experimental animals (continuous line) were given both metals in a single injection (0.5 ~xmoles each). Solid symbols indicate significant differences from the control. Ordinate: organ content of 2~ (left hand graph) of 7~Se (right hand graph) expressed as percent of the dose. The 6 h values for 2~ are the mean of 10; at 24 h the numbers are the same as in Tables 1 and 2 and all the other points are the mean of 6
zo3
IO0
Hg
"t5 Se
to
% IO
OI 6
24
I 48
48 6 24 Hour5 ofter treQtment
2. Effect of equimolar doses of selenite on the distribution of 2~ methylmercury chloride. Methylmercury chloride was given by gastric gavage (in 5 ml/kg saline) either alone or mixed with selenite Table
Dose in ~moles/kg
Organ
2~
contents in % of the dose (mean _+ SEM)
24 h after administration
48 h after administration
Control N=4
Experimental N=4
1.25
Blood Brain Liver Kidneys
48.8 0.34 6.55 4.25
_+ 1.11 _+0.05 + 0.46 + 0.25
43.6 0.74 6.10 3.88
+ 1.65 + 0.03* + 0.61 _+0.46
2.50
Blood Brain Liver Kidneys
50.4 0.22 7,10 3.68
_+ 1.96 + 0.07 + 0.49 _+0.38
35.9 1.08 6.52 2.45
+ 0.75* + 0.02* _+0.29 + 0.35
5.0
Blood Brain Liver Kidneys
55.5 0.26 6.35 4.10
_+ 2.78 + 0.02 + 0.30 + 0.04
39.3 1.19 5.98 2.63
+ 0.93* + 0.24* _+0.43 + 0.10"
Control N=4
Experimental N=4
42.6 0.33 5.55 3.58
38.6 0.96 5.12 3.28
+ 1.74 +_0.01 + 0.38 + 0.19
+ 2.24 + 0.03* _+0.30 + 0.20
* Significantly different from the control with the Student t test: P < 0.01
F r o m F i g u r e i w h i c h s h o w s t h e v a r i a t i o n w i t h t i m e in t h e brain, k i d n e y a n d b l o o d c o n t e n t s o f 2~ o r 75Se w h e n t h e m e t a l s w e r e i n j e c t e d a l o n e o r m i x e d t o g e t h er, it a p p e a r s t h a t t h e i n t e r a c t i o n i n c r e a s e d the b r a i n c o n t e n t o f 2~ more than the b r a i n c o n t e n t o f 755e at a n y time. F r o m 6 - 4 8 h t h e r e w a s a s t e a d y decline in the b r a i n c o n t e n t o f 2~ c o r r e s p o n d i n g t o 0 . 2 % o f the d o s e p e r 24 h in a n i m a l s w h i c h
The Effect of Selenium on the Brain Uptake of Methylmercury
205
Table 3. The brain and blood concentration of 2~ after the intragastric administration of 5 Fxmoles/kgMeHgCIin controlrats givenequivalent doses of Na2SeO3 2, 3 and 7 days after methylmercury. Animals were killed 24 h after treatment with selenite or equal volume of saline. Numbers in brackets are brain concentration corrected to 19 mg blood/g brain. There are 6 animals per group Treatment
~g Hg/g tissue (mean • SEM)
in days after MeHgC1
Brain
Blood
Control
Experimental
Control
Experimental
2
0.38 + 0.01 (0.28 • 0.01)
0.89 + 0.05* (0.81 • 0.05)
5.20 + 0.07
4.40 + 0.09*
3
0.32 • 0.01 (0.20 f 0.01)
0.65 • 0.02* (0.57 + 0.02)
4.56 • 0.14
4.00 • 0.08*
7
0.34 • 0.01 (0.27 • 0.01)
0.64 + 0.05* (0.56 + 0.04)
3.69 • 0.15
3.72 • 0.14
* Significantly different from the control with the Student t test: P < 0.005
were given selenite. Differences in mercury contents of blood and kidneys caused by the simultaneous administration of selenite were also the highest 6 h after adminstration. Table 2 shows that the effect of selenite on the brain contents of 2~ was significant when equimolar doses of selenite were administered by gastric gavage with Me2~ The increase in the brain content of 2~ was the smallest at the lowest (1.25 ~xmoles/kg) dose level and highest at the highest (5.0 ~moles/kg) dose level. The blood and kidney contents of 2~ decreased as after subcutaneous administration. At 48 h after administration selenite-treated animals also had significantly more 2~ in the brain than rats given only Me2~ Two way analysis of variance of the brain contents of 2~ indicated a highly significant effect of selenite (F = 1073; P
Arch. Toxicol. 38, 201--207 (1977)
TOXICOLOGY 9 by Springer-Verlag 1977
The Effect of Selenium on the Brain Uptake of Methylmercury* L. Magos** and M. Webb MRC ToxicologyUnit, Medical Woodmansterne Road, Carshalton, Surrey, SM5 4EF, Great Britain
Abstract. Twenty-four h after the subcutaneous administration of 0.5 pxmoles selenite labelled with 755eto rats of 200 g body weight, the retention of selenium at the injection site was significantly increased by the presence of equimolar amounts of methylmercury in the injection solution. The retention of Me2~ was not affected by the presence of selenite. The most significant shift caused by interaction was a decrease in the blood content and an increase in the brain content of 2~ The brain content of 75Sewas also increased to a lesser extent. The shift in the distribution - which was the same whether the two metals were injected at the same site or separately -- continuously decreased from 6 - 4 8 h. The same interaction pattern was observed when methylmercury and selenite were administered by gastric gavage and differences in distribution increased when the dose was increased from 1.25 ~moles/kg to 2.5 ~moles/kg. The increase in the brain content of mercury caused by selenite was not restricted to simultaneous administration and occurred when selenite was given 2 - 7 days after methylmercury.
Key words: Methylmercury -- Selenium -- Brain - Blood - Interaction.
Introduction Selenium is able to decrease the toxicity of methylmercury in food (Ganther et al., 1972; Stoeswand et al., 1974; Stillings et al., 1974), although recently Ohi et al. (1976) observed that selenium in tuna fish was approximately half as efficient as selenite in the prevention of the neurological effects of methylmercury. The mechanism whereby selenium protects against the toxicity of methylmercury is not known, but it is certain that selenium in some form affects the organ distribution of methylmercury after various days of feeding schedule: selenium supplement seems to in* Supported partly by International Atomic Energy Agency Grant Number 1530/RB ** To whom offprint requests should be sent
202
L. Magos and M. Webb
crease the mercury concentration in the liver, spleen (Potter and Matrone, 1974) and in the brain (Ohi et al., 1975), although in the latter organ this effect can be absent (Ohi et al., 1976). This discrepancy might be explained by the difference in food intake or by the timing of the observation. Thus Iwata et al. (1973) observed that at 24 h after the last of 8 - 1 0 daily injections of methylmercury and selenium the brain accumulation of mercury was higher than in rats given methylmercury alone, whereas 6 days later it was lower. With the progress of intoxication, decreased food consumption with resultant drop in the intake of methylmercury and selenium, shift in metabolic balance, deficient kidney and liver functions are all likely to contribute to a change in the pattern of distribution and excretion of toxic metals. As it is difficult to interpret differences in distribution after multiple doses without knowledge of how the interacting metals behave after a single dose, a study has been made of the interaction between selenium (as Na2SeOa) and methylmercury (as CH3HgC1) by the single-dose experimental schedule that has been used in previous work (Magos and Webb, 1976a, b). Both compounds were injected subcutaneously alone, in combination as a single injection, or at different sites; organ contents and retention at the injection sites being determined usually after 24 h. Because of the importance of per os uptake, in some of the experiments the administration of selenite a n d / o r methylmercury was by gastric gavage, the selenite being given either together with methylmercury or 2, 3 or 7 days later.
Methods and Materials Injection Solutions. Cold stock solutions of MeHgC1 (K & K Laboratories Inc., Plainview,N.Y., USA)
or Na2SeO3 (BDH Chemicals Limited, Poole, England) were prepared in saline and were labelled with the corresponding isotope (Me2~ or Ne275SeO3)supplied by the Radiochemical Centre (Amersham, Bucks., England). Volumes of the subcutaneous injection solutions were 0.2 ml and they contained 0.5 ~moles MeHgC1 or Na2SeO3or both. Only one of them was labelled.For per os experiments solutions were prepared from the stock solutions and contained 1.25, 2.50 or 5.0 ~moles MeHgC1 in 5 ml saline with or without equivalent concentration of selenite, or 5.0 ~moles selenite alone if their administration was not simultaneous. They were injected by gastric gavage in a dose of 5 ml/kg. Animals in each experiment were injected either with 0.1 ~xCi2~ or 0.06 ~Ci 755e. Experimental Schedule. Male rats of Porton Wistar strain of approximately 200 g body weight were
used. In one group of experiments methylmercury chloride (MeHgC1) or Na2SeO3, or a mixture of the two, was injected subcutaneously into the right hind leg above the knee. In the second group of experiments, instead of injecting the mixture of MeHgC1 and Na2SeO3, the radioactively labelled compound was injected into the right hind leg, and the other under the neck. In the third group of experiments either MeHgC1 or Na2SeO3, or their mixture, was administeredby gastric gavage. Animals were killed by decapitation 6, 24 or 48 h after treatment. Blood from cervical vessels was collected in a beaker and was weighed. Liver, kidneys and brain (cerebrum, cerebellum and brain stem) were removed. Hind legs were removed by cutting through the hip joint. Radioactive Measurements. Live animals placed in a 14 x 6 x 6.5 cm plexiglass box were counted with
an efficiency of 9.6% for 2~ and 23.3% for 7~Se between two Nal crystal pairs (No. N656, Ekco Electronics Limited, Southend-on-Sea,Essex, England) facing each other. Faeces, urine, legs and organs were counted in a well-shaped NaI crystal (13 cm diameter, 11 cm depth), counting efficiencies being 43.0% for 2~ and 90.4% for 75Se.Injection standards in 1 ml acid permanganate solution were counted and metal contents in organs, excreta or in the whole animals were estimated after corrections for geometrical differences by relating their radio-activitiesto the standards. Radioactivity retained at
The Effect of Selenium on the Brain Uptake of Methylmercury
203
the injection site was determined from the difference between the injected and the control leg. Radioactivity in the total blood was calculated on the assumption that blood made up 7.0% of the body weight. Statistical Calculations. Statistical differences were estimated by the two tailed Student t test for
correlated groups for results presented in Tables 1, 2 and 3. The statistical differences in Figure 1 were calculated by the Student t test for independent means (two tailed test) and the selenium effect on the brain data and its dependence on time was calculated by the two-factor analysis of variance.
Results T a b l e 1 c o m p a r e s the retention, distribution and e x c r e t i o n o f 2~ and 7~Se after the s u b c u t a n e o u s a d m i n i s t r a t i o n o f Me2~ or Na275SeO3 with o r w i t h o u t the simult a n e o u s a d m i n i s t r a t i o n o f the o t h e r c o m p o u n d at the s a m e site. Selenite h a d no effect o n the r e t e n t i o n o f Me2~ at the injection site, d e c r e a s e d the c o n c e n t r a tion o f 2~ in b l o o d and kidneys and i n c r e a s e d it in the b r a i n a n d urine. M e t h y l m e r c u r y injected with selenite i n c r e a s e d the r e t e n t i o n o f 75Se at the injection site, a n d d e c r e a s e d the k i d n e y and liver c o n t e n t s o f 75Se. T h e b r a i n c o n c e n t r a t i o n o f 755e w a s i n c r e a s e d but n o t significantly. E x p e r i m e n t s in w h i c h the unlabelled c o m p o u n d w a s given at a different site s h o w e d a similar shift in the distribution o f 2~ or 7~Se with the e x c e p t i o n t h a t the retention o f 75Se w a s n o t affected b y M e H g C 1 . B r a i n c o n t e n t s w e r e n o t c o r r e c t e d to b l o o d value, but c o r r e c t i o n should increase a n d n o t d e c r e a s e the difference b e t w e e n the c o n t r o l a n d the selenite group. A s the w e i g h t o f b r a i n in 200 g rats is a p p r o x i m a t e l y 1.9 g, and the b l o o d c o n t e n t o f b r a i n in e x s a n g u i n a t e d animals is 19 m g / g ( W a n n a g , 1976), v a l u e s for b r a i n m e r c u r y p r e s e n t e d in T a b l e 1 should d e c r e a s e b y 0.11 for c o n t r o l s a n d 0.09 for selenite-treated rats. T h e corres p o n d i n g c o r r e c t i o n s for 755e are 0.013 and 0.012 respectively.
Table 1. The distribution of 2~ or 75Se 24 h after subcutaneous injection of 0.5 p,moles Me 2~ or Na2VSSeO3.The compounds were given either alone or (control) or in combination (experimental), when one component was not labelled Radioactivity in % of the dose (mean + SEM)
755e
Injection site Body burden Blood Brain Liver Kidneys Urinea Faecesa
2O3Hg
Control N = 10
Experimental N = 10
Control N=20
Experimental N=20
0.34+0.05 46.2 + 2.50 5.1 +0.24 0.10 _+0.01 11.5 _ 0.75 2.7 + 0.20 33.0 _+0.90 8.1 + 1.19
6.0 43.1 4.8 0.14 8.1 2.0 31.3 5.8
9.8 93.3 43.6 0.15 5.9 4.6 0.21 1.6
8.62-+ 1.11 95.6 _+0.95 36.0 + 1.21" 0.66 _+0.03* 5.21 _+0.2 2.7 -+ 0.09* 0.35 + 0.03* 1.6 + 0.21
_+0.53* + 1.11 +0.36 + 0.02 _+ 0.39* + 0.13" + 1.19 + 3.84
+0.28 + 2.56 + 1.56 + 0.02 _+0.23 + 0.45 _+0.02 +0.13
a N for excreta is half that for other samples, as one sample was collected from 2 animals * Significantly different from the control with the two tailed Student t test: p < 0.01
204
L. Magos and M. Webb
Fig. 1. The effect of interaction between Na2SeO 3 and MeHgC1 on their contents in blood (squares); brain (circles) and kidneys (triangles). Controls (broken line) were given only one metal subcutaneously in a dose of 0.5 ~moles per animal; experimental animals (continuous line) were given both metals in a single injection (0.5 ~xmoles each). Solid symbols indicate significant differences from the control. Ordinate: organ content of 2~ (left hand graph) of 7~Se (right hand graph) expressed as percent of the dose. The 6 h values for 2~ are the mean of 10; at 24 h the numbers are the same as in Tables 1 and 2 and all the other points are the mean of 6
zo3
IO0
Hg
"t5 Se
to
% IO
OI 6
24
I 48
48 6 24 Hour5 ofter treQtment
2. Effect of equimolar doses of selenite on the distribution of 2~ methylmercury chloride. Methylmercury chloride was given by gastric gavage (in 5 ml/kg saline) either alone or mixed with selenite Table
Dose in ~moles/kg
Organ
2~
contents in % of the dose (mean _+ SEM)
24 h after administration
48 h after administration
Control N=4
Experimental N=4
1.25
Blood Brain Liver Kidneys
48.8 0.34 6.55 4.25
_+ 1.11 _+0.05 + 0.46 + 0.25
43.6 0.74 6.10 3.88
+ 1.65 + 0.03* + 0.61 _+0.46
2.50
Blood Brain Liver Kidneys
50.4 0.22 7,10 3.68
_+ 1.96 + 0.07 + 0.49 _+0.38
35.9 1.08 6.52 2.45
+ 0.75* + 0.02* _+0.29 + 0.35
5.0
Blood Brain Liver Kidneys
55.5 0.26 6.35 4.10
_+ 2.78 + 0.02 + 0.30 + 0.04
39.3 1.19 5.98 2.63
+ 0.93* + 0.24* _+0.43 + 0.10"
Control N=4
Experimental N=4
42.6 0.33 5.55 3.58
38.6 0.96 5.12 3.28
+ 1.74 +_0.01 + 0.38 + 0.19
+ 2.24 + 0.03* _+0.30 + 0.20
* Significantly different from the control with the Student t test: P < 0.01
F r o m F i g u r e i w h i c h s h o w s t h e v a r i a t i o n w i t h t i m e in t h e brain, k i d n e y a n d b l o o d c o n t e n t s o f 2~ o r 75Se w h e n t h e m e t a l s w e r e i n j e c t e d a l o n e o r m i x e d t o g e t h er, it a p p e a r s t h a t t h e i n t e r a c t i o n i n c r e a s e d the b r a i n c o n t e n t o f 2~ more than the b r a i n c o n t e n t o f 755e at a n y time. F r o m 6 - 4 8 h t h e r e w a s a s t e a d y decline in the b r a i n c o n t e n t o f 2~ c o r r e s p o n d i n g t o 0 . 2 % o f the d o s e p e r 24 h in a n i m a l s w h i c h
The Effect of Selenium on the Brain Uptake of Methylmercury
205
Table 3. The brain and blood concentration of 2~ after the intragastric administration of 5 Fxmoles/kgMeHgCIin controlrats givenequivalent doses of Na2SeO3 2, 3 and 7 days after methylmercury. Animals were killed 24 h after treatment with selenite or equal volume of saline. Numbers in brackets are brain concentration corrected to 19 mg blood/g brain. There are 6 animals per group Treatment
~g Hg/g tissue (mean • SEM)
in days after MeHgC1
Brain
Blood
Control
Experimental
Control
Experimental
2
0.38 + 0.01 (0.28 • 0.01)
0.89 + 0.05* (0.81 • 0.05)
5.20 + 0.07
4.40 + 0.09*
3
0.32 • 0.01 (0.20 f 0.01)
0.65 • 0.02* (0.57 + 0.02)
4.56 • 0.14
4.00 • 0.08*
7
0.34 • 0.01 (0.27 • 0.01)
0.64 + 0.05* (0.56 + 0.04)
3.69 • 0.15
3.72 • 0.14
* Significantly different from the control with the Student t test: P < 0.005
were given selenite. Differences in mercury contents of blood and kidneys caused by the simultaneous administration of selenite were also the highest 6 h after adminstration. Table 2 shows that the effect of selenite on the brain contents of 2~ was significant when equimolar doses of selenite were administered by gastric gavage with Me2~ The increase in the brain content of 2~ was the smallest at the lowest (1.25 ~xmoles/kg) dose level and highest at the highest (5.0 ~moles/kg) dose level. The blood and kidney contents of 2~ decreased as after subcutaneous administration. At 48 h after administration selenite-treated animals also had significantly more 2~ in the brain than rats given only Me2~ Two way analysis of variance of the brain contents of 2~ indicated a highly significant effect of selenite (F = 1073; P
