Effect of tin compounds on activity of 5-aminolevulinate dehydratase in blood

Vol. 82, No. 4, 1978

BIOCHEMICAL

AND BIOPHYSICAL

RESEARCH COMMUNICATIONS

Pages 1057-1061

June 29, 1978

EFFECT OF TIN COMPOUNDSON ACTIVITY OF 5-AMINOLEVULINATE Momoko Chiba

April

and Masakazu

Kikuchi

Department of Hygiene, University School of Medicine, Tokyo 113, Japan

Juntendo Received

DEHYDRATASE IN BLOOD

17, 1978

SUMMARY Erythrocyte 5-aminolevulinate dehydratase activity was measured in rabbits administered with tin(I1) or tin(IV). A significant decrease in enzymic activity was observed in the case of tin(II), while any significant effect was not detected in the case of tin(W). It (ALAD,

is well

known that

EC 4.2.1.24),

biosynthetic

On the other those

which

pathway,

has a protective

effect hand,

on other

and small

metals

inhibits

this

From further to be restricted

is

is

the

inhibited against

by lead this

probably of tin.

experiment, only

on tin

We have studied

blood inhibitory

to bivalent

2),

is

and zinc

(3,

4, 5).

fewer

than

rapid

excretion

the effect

and we found

in rabbit this

(1,

inhibition

due to the

on ALAD activity, activity

dehydratase

second enzyme in porphyrin

number of reports

metals,

toxicity

several

5-aminolevulinate

that

tin

significantly effect

of

(6). was found

tin.

MATERIALS AND METHODS Adult male white rabbits, weighing Animals and tin solutions. Tin compounds used were stannous 2.5~ 3.5 kg. were used. stannic chloride (SnC14), and stannous chloride (SnC12*2H20), citrate [Sn(OH)Sn(C6H507)]. A solution of 5 pmol of each compound dissolved in 0.5 ml of 5% glucose was injected per The animal kg of body weight via the marginal ear vein. number of rabbits, kinds of tin solutions, and pH groups, There are value of the solutions are listed in Table I. various tin derivatives but the kinds of compounds suitable for our experiment are limited by its insolubility and tin is readily oxidized by unstability. Since the bivalent air to tetravalent, the solutions for Groups C and D were 0006-291X/78/0824-1057$01.00/0 1057

Copyright All rights

0 1978

by Academic Press, Inc. in any form reserved.

of reproduction

BIOCHEMICAL

Vol. 82, No. 4, 1978

Table

I.

Rabbit

RESEARCH COMMUNICATIONS

and treatment

Group

n

A B

7

-

3

-

5% glucose 5% glucose

C D E

4

II

SnC12*2H20

4 2

IV II

F

3

IV"

SnC14 Sn(OH)Sn(C6H507) SnC12* 2H20*

* This after

Valence

group

AND BIOPHYSICAL

Administered

pH of

solution

solution

5.89 1.95 (with dil.

HCl)

3.23 1.95 3.30 3.20

solution was kept at room temperature for 50 days preparation, and Sn2+ could not be detected.

prepared immediately before injection. The solution for Group F was the same solution used for Group C after leaving at room temperature for 50 days, as tin(W). Absence of for Groups D and F was confirmed by Sn2+ in the solutions colorimetoric method using toluene-3,4-dithiol (7). Animals in Groups A,B,C, and D were injected onceaday for three consecutive days. Those in Groups E and F were injected once. Blood was collected from the Measurement of ALAD activity. marginal ear vein into heparinized small tubes and immediately kept on solid carbon dioxide to hemolyze erythrocytes. This hemolyzed sample was used as the sorce of enzyme. The assay method of the enzymic activity was the same as that described in our previous paper (8). RESULTS AND DISCUSSION In Groups A, B, C, and D, ALAD activity 3, 4, 7, 10, 15, results

are

and 24 daysafterthe

shown in Fig.

of tin(I1)

on blood

of tin(IV);

tin(I1)

after

only

is nearly

a single the

showed no effect

first

It

injection,andthe

is clear

ALAD activity

is

significantly

decreases

injection.

same effect

is known to inhibit

1.

was measured 1, 2,

This

far

on the activity.

from that

of (9),

of

lead/kg, but

TO examine whether

1058

effect

the activity

drop by tin

markedly

the

different

of 1 mg (5 pmol)

ALAD activity

that

5 pmol/kg which tin(IV) the

Vol. 82, No. 4,1978

8lOCHEMlCAL

I2

34

AND BIOPHYSICAL RESEARCH COMMUNICATIONS

7

IO

15

24 ( Days)

7tt

Figure

observed

ALAD activity in blood from rabbits injected -iv with 5 umol of tin per kg (0) Group A (control), (m) Group B (control (A) Group C [tin(II)], (v) Group D [tin(IV) 1‘ Injection 1 &SD

1.

difference

between

phenomenon associated general tin,

with

characteristic

following

experiment

and those

with

by atomic

result

shown in Table

the ALAD activity We attempted

Group D or F, but Effect

of

was estimated

lead

II.

It

with

in rabbit

toxicity

the

storage

was This

that

this

on the result

1059

standing

tin(I1)

does

but

tin

not

50 pmol of tin(IV)/kg

prevented

absorption

of

Group F,

erythrocytes of

of

as tin

50-day for

was proved

contamination

by atomic

solution

spectrophotometry.

to administer its

The rabbits

In the solution

absorption

a

in the valence

citrate

during

is

I,

compounds or a

out.

stannous

concentration

confirmed

(IV).

tin

was carried

as tin(N).

no change in tin

inhibit

specific

of Group F were injected

SnC12 solution,

is

the

and tin(IV)

due to difference

Group E were injected (II),

tin(I1)

.I I

experiment. of

spectrophotometry

tin(I1) applied

to

BIOCHEMICAL

Vol. 82, No. 4, 1978

Table

ALAD activity

II.

AND BIOPHYSICAL

RESEARCH COMMUNICATIONS

in Groups E and F

ALAD activity* Group

Before

E (Sn2+)

F (Sn4+)

injection

solution

the

was not

former

0.16

1.18

1.16

1.10 1.14

1.06

0.04

1.11

detectable

of lead

by injection

with

excreted

This

organism. that

tin

is not

and systemic reported

and the

being

converted

assumption rapidly

is

the

supported

of

blood

form

by Hiles'

in rats

in the

statment

during

Furtheremore,

tin(I1)

triggered

may be

toxic

or reduced

(10).

absorption

the

that

possible

Tin(W)

into

oxidized

was confirmed

latter,

was negligible.

transportation

that

It

from the bone into

tin,

without

erythrocytes/h 5 pmol tin/kg

of

and sample blood.

mobilization

injection**

1.23 1.19

* unit: pmol porphobilinogen/ml ** At 24 h after -iv injection

to the tin

After

absorption Hiles

(10)

was faster

than

tin(W). Although activity lead

it

and it exposure,

conjecture. the difference

is well

known that

is one of its

Tin(I1)

the useful

inhibitory also

lead

decreases

indices

to evaluate

mechanism still decreases

in mode of action

remains

ALAD activity,

between

ALAD

lead

a

and

and tin

must

be elucidated. REFERENCES 1. Lichtman, H. C., 42, 830-839.

and Feldman,

F.

1060

(1963)

J.

Clin.

Invest.

Vol. 82, No. 4, 1978

BIOCHEMICAL

AND BIOPHYSICAL

RESEARCH COMMUNICATIONS

2. de Bruin, A. (1968) Med. Lab. 59, 411-418. V. N., Murthy, L., Pezano, W. B., and Petering, 3. Finelli, H. G. (1974) Biochem. Biophys. Res. Commun. 60, 1418-1424. 4. Finelli, V. N., Klauder, D. S., Karaffa, M. A,, and Petering, H. G. (1975) Biochem. Biophys. Res. Commun. 65, 303-311. 5. Thomasino, J. A., Zuroweste, E., Brooks, S. M., Petering, H. G., Lerner, S. I., and Finelli, V. N. (1977) Arch. Environ. Health 32, 244-266. 6. Chiba, M., and Kikuchi, M. (1974) Sangyo Igaku 16, 226-227. 7. Ishidate, M. (1966) Quantitative Microanalysis (in Japanese), PP- 195-198, Nanzando, Tokyo. 8. Chiba, M., Tashiro, A., Nishima, T., and Kikuchi, M. (1976) Ind. Health 14, 67-74. 9. Chiba, M., and Kikuchi, M. (1974) Sangyo Igaku 16, 531-545. 10. Hiles, R. A. (1974) Toxicol. Appl. Pharmacol. 27, 366-379.

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