Effect
of Agroclavine on NK Activity in Vivo under
Normal and Stress Conditions in Rats
M.
STAREC, A. FIŠEROVÁ3, J. ROSINA1,
J. MÁLEK2, M. KRŠIAK
Department
of Pharmacology, 1Department of Biophysics,
2Department of Anesthesiology, Third Faculty of
Medicine, Charles University, and 3Institute of
Microbiology, Academy of Sciences, Prague, Czech
Republic
Received October 17,
2000
Accepted February 19, 2001
Summary
Agroclavine
is a natural, clavine type of ergot alkaloid with
D1 dopamine and ?-adrenoceptor agonistic
properties. We showed previously that in vitro
agroclavine enhances natural killer (NK) cell
activity, increases interleukin-2 and
interferon-gamma production and prolongs the
survival time of tumor-bearing mice. The aim of
this study was 1) to test the effect of
agroclavine on NK activity in vivo, and 2) to
assess the potential toxicity of high doses of
agroclavine on cardiac and liver functions using
creatine kinase MB (CKMB) and alanine
aminotransferase (ALT) as biochemical markers in
normal and stressed animals. The effect of stress
was studied because we examined promising
anticancer properties of agroclavine and
malignant diseases are supposed to be a potent
stressful event for patients. In our experiments
3-month-old male rats of the Wistar-Kyoto strain
were used. Agroclavine was injected
intraperitoneally (0.5 mg/kg or 0.05 mg/kg) 30
min before stress (four hours' restraint and
immersion in 23 °C water). The animals were
killed 30 min after stress, blood was collected
and the spleen was removed. Non-stressed animals
treated with agroclavine were killed 5 h after
the drug administration. The results confirmed
our previous in vitro results and showed that
also in vivo agroclavine increases NK cell
activity under non-stress conditions. Agroclavine
only slightly increased CKMB and had no influence
on ALT in non-stressed animals. These promising
results are limited by the fact that agroclavine
(0.5 mg/kg) diminished NK cell activity and
significantly increased ALT and CKMB under stress
conditions.
Key
words
Agroclavine
· Ergot alkaloid · Stress · Rat · NK cell
activity · Toxicity
Reprint
requests
Dr.
Miroslav Starec, Department of Pharmacology,
Third Faculty of Medicine, Charles University,
Ruská 87, 100 00 Praha 10, Czech Republic, fax.
0042 2 67102461, e-mail Miroslav.Starec@LF3.cuni.cz
|