Enhancement of Erythrocyte Superoxide Dismutase ...

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Enhancement

of Erythrocyte Effects

By To

delineate

(SOD) the

further

in

human

Mark

red

blood

This

RBC

the

control

cell

a five-

drugs

No

between

B

VIRTUE

their

OF

(RBCs)

normal

or

are

RBCs

exposed

physiologic

role,

little

(SOD), which to hydrogen

catalase

(GSH)

and

and

the

glutathione

of H202 tripeptide

reduction

of

peroxidase,

well as methemoglobin

the

oxyhemoglobin; brane-bound

activity reductase,

and molecule

(f)

cells

that

of cell

activated consists of the dismu(H202); (b)

which

azide

showed

block

significantly

No differential

response

than

to

the

02

by Grune

noted

on

elevated

SOD

conditions

and

activity

may

in enhanced of

effect

in which

to

results

generation This

genbetween RBCs

our

resulting

accelerated

& Stratton.

enhanced

SOD-loaded

defense.

dismutation.

under

was

Based

that

oxidant

catadeplete

to superoxide

and

superoxide.

conclude

due

(to

(to

in response

we

of

is

H2O2,

the

significantly

H2O2

catabolism

is

Inc.

the

RBC

conditions

an insufficiency in the 6-phosphate dehydrogenase

oxidant

defense

are believed

by either increased 5, RBC-active oxidant antioxidant (G6PD)

by

variants

lysis.7

necesof GSH,

models We

with

for

SOD

these

ghosts

methods

the

a modification

antioxidants have relied on

through

have

reversible

limitations

RBC antioxidant and simplification

as

system. of the dialysis

method8’9 by which large macromolecules can loaded into RBCs. These cells exhibit normal cellular deformability, and oxidant sensitivity.

be efficiently morphology, used

of

understanding

report

To define

or membrane

all

or

glucosePrevious

characteristics,4’5 the enzymes,6 or enzyme-

antioxidant

of antioxidant

of liposomes

However,

lysis/resealing

we

altered

inactivation

to arise

generation drugs)

system (eg, deficiency).2’3

attempts to understand the role of intracellular in preventing oxidant-mediated RBC damage

loading

and nonlipid radical species. Although the normal RBC reducing capacity is greater than 250 times its oxidizing potential’ several RBC abnormalities have been identified

hemolytic

damage caused (eg, hemoglobin

of oxidants

hexose

a memboth lipid

or overwhelm

several

oxidative

of H202

of other enzymes; (e) NADHwhich reduces methemoglobin to vitamin E (ct-tocopherol), that efficiently scavenges

Indeed, by

selective

a small

the NADPH regeneration

circumvent

system.

RBC

catalyze

the

(d)

groups;

shunt, which generates for the GSH reductase-dependent

as

blood

to H2O and 02; (c) GSH, used in the degradation sulfhydryl

GSH)

cellular

1989

sodium

elevated

red

catalyzes peroxide

monophosphate sary

0

with

H. Lubin

1 -chloro-2.4-dinitrobenzene

control-resealed,

exacerbated

thiobarbituric

Bertram

generation

other data,

altered.

generated primarily

(a) superoxide dismutase of superoxide (02)

control.

product

observed

and

glutathione, drugs.

in 02-driven with

or

imbalance

oxidative stress; yet evidence of cumulative

and exogenously antioxidant system

reduced

Chiu,

pretreated

oxidation

This may reflect the efficacy system, which protects the

tation

the degradation thiol-containing

of RBCs

show

damage. defense

from endogenously oxygen. The RBC

generation

In contrast,

activity)

other

activity sodium

were

activity

lase

oxidants

superoxide-gener-

RBCs

to continuous

generally

oxidant-mediated the RBC oxidant

SOD

T.-Y.

SOD

the

nor-

deformability. in

Daniel

erating

from

Activity:

Defense

methemoglobin

activity

or menadione

SOD-loaded

substances.

in

nearly

cellular

increase against

Kuypers,

SOD.

decrease

differences

and

formation

acid-reactive

and

methosulfate

control

methemoglobin

maintaining

ninefold

significant

the

resealed

in SOD

(