Ascorbic

acid and adriamycin

Kan Shimpo, Toshiharu Tomio Takeuchi, Hamao

Nagatsu, Keiki Yamada, Umezawa, and Keisuke

ABSTRACT

Adriamycin

(ADR)

range

neoplasms.

However,

of human

promised

by serious

of peroxidation tioxidant, mice tumor

examined

ascites

life of animals levels

in mouse

guinea

with

heart,

and

ADR

and

the

and also prevent the clinical acid

1298S-

l3OlS.

KEY WORDS bic acid,

proved may

the cardiac

toxicity.

ofthe

delay

anthracycline

antibiotic

general

in

toxicity

of

ofADR

Nutr

and

1991 ;54:

approach a derivative

tibiotic with low heart toxicity. 4’-O-tetrahydropyranyl-adriamycin, cardiac toxicity (5). Another approach

may

by the combined the

is effective

ADR

and ascorbate

Ascorbate

the

of ADR-induced

of ADR of the

(6-8),

the usefulness

cardiac

other

10). is also

in the reports

that

treatment

administration

of

drugs.

Al-

antitumor

ing

ICR

itself

acid

of cancer patients ascorbate

2-O-octadecylascorbic

as a protectant a potent

prolongs

against

survival

time

(CV-36

to-

questioned

are

also

inter-

in the supportive in terminal

examined ascorbate

1 1 ) ( 14) and

human

the effect

of

derivatives, ascorbyl

Am J C/in Nuir

was

(0.5

traperitoneally

CV-36l

ofADR

As-

curves ascorbate

receiving

both

1. no

significant

and

effect.

In

administration

of

the life of mice with

Ll2 10

after

ofADR.

ascites

three

(50

pal-

I 99 1;54: 12985-

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palmitate

(2 g/kg),

mg/kg)

day for 12 d. The

on

carcinoma-bear-

intraperitoneal

Ascorbate

palmitate

every

1, and ascorbyl

in Ehrlich

examined

mg/kg)

or ascorbyl

was

adminCV-36

1 1 (50

administered

survival

in-

curves

for the

control (solvent alone); the groups given ascorbate, CV-36l or ascorbyl palmitate; the group given ADR; and the group

but CV-36l ascites

1 and

ascorbyl

palmitate

ofantitumor

ADR

effect

and ascorbyl

of ascorbate

In an experiment

ofADR

1, or ascorbyl

(Fig 2). A significant

(Fig 3).

on toxicity

of ADR

repeated

in the life span

ofmice

effect,

the life of Ehrlich

was observed

palmitate

with

1, re-

palmitate

had no significant

prolonged

ICR mice

carcinoma-bearing

4), an increase

ADR-induced

We

ascorbate

(1 1 , 12). We therefore (1 3), and two lipophilic acid

have

antioxidant.

previous

scavenger

publications

supplemental

by

had

prolonged

ascorbate. survival

given

in after

and

the group

alone

of ADR

The

the group

and

in Figure

of ADR

action

mice

tentiation

is unex-

reduced

free-radical

day.

alone),

ceiving both ADR and ascorbate, CV-361 are shown in Figures 2 and 3. Ascorbate

toxicity

cardiotoxicity

to be the

recent

oftocopherol (9,

found with

although

cardiotoxicity

l298S

were

animals

ICR

was examined

of ADR

alone,

are shown

administration

the

Effect

toxicity

treatment

cancer sodium

ADR

effect

cells

every

solution

given

both ADR and ascorbate leukemia (P < 0.01).

diac

Ascorbic

(5 mg/kg)

(0.9% NaCl

contrast,

Ll2lO

was administered

the group

with

ested

on the antitumor leukemia

administration

for control

plained, one probable pathway is the induction of peroxidation in cardiac lipids (6). Thus, both this lipid peroxidation and car-

copherol

of ascorbate

(2 gJkg)

mg/kg),

et al (4) synthesized had a low delayed

of some

mice,

effect of ADR in leukemia L1210 cells

on antitumor

transplanted

istrations

to potentiate the clinical of the antitumor an-

be to prevent

administration

mechanism

(ADR)

Umezawa which

in BD2F1

Effect of ascorbate, CV-361 1 and ascorbyl palmitate on antitumor effect of ADR in Ehrlich ascites carcinoma-bearing ICR mice

neoplasms ( 1 ). Unfortunately, by a potentially lethal cardiac

toxicity (2, 3). One significant value of ADR is to discover

though

effect with

alone,

also sug-

2-O-octadecylascor-

adriamycin

of ADR

pigs.

mice with transplanted

corbate

toxicity

range of human is compromised

Shamoto,

lethality

guinea

The effect of ascorbate,

against a wide its clinical use

ADR

the

Hartley

of ascorbate

The mice

Introduction The

Mikihiro

(I 5, 16), on

a single

microscopy.

J Clin

ascorbate,

palmitate,

the

the elevation.

treatment

Am

Niimi,

and

Effect BD2F1

antiLl2lO

peroxide

The results

combined

Adriamycin,

ascorbyl

lipid

by electron

derivatives.

the

in

cardiomyopathy

derivatives

efficacy or the

was

an-

toxicity

prolonged

prevented

ofADR-induced acid

mice,

ADR

elevated

acid

mitate

no effect on with leukemia

ADR

ascorbic

prevention

acid

ascorbic

ADR.

a wide

a potent

but it significantly

Hajime

induction

acid,

in reducing

Sato,

use is com-

through

Ascorbic

acid had inoculated

Taizan Fujita

against

its clinical possibly

lipids.

carcinoma,

pigs by ascorbic

Ascorbic

toxicity,

Ascorbic in mice

treated

The significant

is effective

for effect

and guinea pigs. activity ofADR

or Ehrlich

gest

cardiac

in cardiac

was

,2

in BD2FI

administration was observed

po-

in the group

mice

of ADR

(Fig

in the group

I From the Institute for Comprehensive Medical Science, School of Medicine, Fujita Health University, Toyoake, Aichi, and the Institute of Microbial Chemistry, Tokyo, Japan. 2 Address reprint nequests to K Fujita, Institute for Comprehensive Medical Science, School ofMedicine, Fujita Health University, Toyoake, Aichi 470-1 1,Japan.

13015.

Printed

in USA.

© I 99 1 American

Society

for Clinical

Nutrition

ASCORBIC

ACID

AND

ADRIAMYCIN

5

“5

4

U-

3

I:

1299S

TOXICITY