Nephrotoxic effects of pepstatin A. An histoenzymologic study

Nephrotoxic effects of pepstatin A. An histoenzymologic study

Pharmacological Research, Vol. 22, Supplement 59 1,199O NEPHROTOXIC EFFECTS OF PEPSTATIN A. AN HISTOENZYMOLOGIC STUDY. BIJSCEMI M.*, GERBINO A.*,...

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Pharmacological

Research,

Vol. 22, Supplement

59

1,199O

NEPHROTOXIC EFFECTS OF PEPSTATIN A. AN HISTOENZYMOLOGIC STUDY. BIJSCEMI M.*, GERBINO A.*, TESSITORE V.*, F.M.#, GEBBIA N.# AND RAUSA L.#. Institute University

of of

Key words: mitochondrial

Pepstatin proven

(*) Italy.

Pepstatin enzymes.

A,

A (Pep), to

tumors

Pep inhibits

have

undertaken

effects

of

were

sacrificed saline

using

by

the

genase)

of

pattern

and

of

enzymes

(Acid

renin

(3),

we the

CD-l

mg/kg

mice

i.p.)

and

DMSO in

parenchyma

were

evaluations

by and

mitochondrial

Isocitric-Dehydrogenase

lysosomal

reported

procedures of

to

also

received

Pep on renal

variations

with

noted

purpose,

group

Mallory-Azan

mice

investigate

and histochemical and

cinil-Dehydrogenase,

to

Pep (200

Control

The effects

Ematoxilin-Eosin

invest,igating

of

later.

morphological

order On this

administrations

(10% v/v).

assessed

in

has been

has been

has been

(#I I enzymes,

in

including

parenchyma.

15 days

lysosomal

agent

As it

studies

Pharmacology

agent

proteinases

further

TUMMINELLO

D inhibitor,

this

(2).

carboxyl

7 and

D,

Cathepsin

effects

single

of

Cathepsin

However

Pep on renal

given

Institute

as antimetastatic

(1).

hepatotoxic

that

and

a specific

be effective

experimental induce

Histology Palermo,

LET0 G.#>

by

(Suc-

and Malic-DehydroPhosphatase,

Acetyl-beta-

Glucosaminidase). Pep administration enzymes

7

granules areas, are

days in

after

renal

completely quite

induced

normal

dramatic

treatment. parenchyma

missing. 7 days

1043-6618/90/2210059-02/$03.00/0

changes Distribution

was disomogeneous On the

following

other

hand,

treatment,

in

mitochondrial of

formazanic

and,

in

some

lysosomes,

which

were

to

noted

o 1990 The Italian Pharmacological

be Society

Pharmacological

60

FIGURE 1: Histochemical the kidney of a mouse

strongly

damaged

chondrial

after

enzymes

evaluation treated with

15 days seem

to

Research, Vol. 22, Supplement I, 1990

of acid Fepstatin

(Figure return

phosphatase (10x) in A (ZOO mg/kg i.p.)

1). to

At a

this

normal

time

mito-

pattern

of

distribution. Further

investigations

induced

by chronic

in

the

are

in

treatments

progress of

to

clarify

Pep on histoenzymatic

the

effects changes

kidney.

REFERENCES 1.

Tumminello F.M. , Let0 G., Gebbia N., Rausa L. and Bernacki R.J. Evaluation of antitumor and antimetatatic activity of Pepstatin A in some experimental tumor models. J. Chemother. 1969, Suppl. 4: 1135-1138.

2.

Buscemi M. ) Gerbino A., Tessitore P.M. and Gebbia N. A morphological hepatotoxicity. Basic and Appl. (Supp?. ):22.

3.

Umezawa H. 1 Aoyagi T. Fepstat.ins, pepstatones, hydroxy-pepstatins-inhibitors of carboxyl proteinases including renin. In: Activities of proteinases inhibitors of microbiological origin. 1979, Chapt. 15:646-651.

Supported

by

AIRC

and

in

part

by

V. , L,eto G., Tumminello study on Pepstatin A Histochem. , 1989, 33

M.P.I.

i60%)