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%)