Cardiac troponin T following repeated administration of pyridoxal isonicotinoyl hydrazone in rabbits.
Pyridoxal isonicotinoyl hydrazone (PIH) is a new tridentate Fe-chelating agent that should be very promising in many pathological states resulting from both an iron-overload and formation of free radicals. The aim of our study was to investigate the effect of PIH on the cardiovascular system focusing to the regulatory protein -- cardiac troponin T (cTnT). The study was carried out in two groups of Chinchilla male rabbits: 1) PIH (50 mg/kg dissolved in 10 % Cremophor i.p., once a week, 10 administrations, n=8) and 2) Cremophor (2 ml/kg i.p. in the same schedule, n=7). Plasma concentrations of cTnT (as a marker of myocardial damage) were measured using a commercial kit (Roche). cTnT was within the physiological range (i.e. < 0.1 microg/l) during the whole experiment in the Cremophor group. In the PIH group, the cTnT levels were not significantly increased when compared with the control group or with the initial values (except with those before the 5th administration). Furthermore, we analyzed the cytosolic and myofibrillar fraction of cTnT in the left ventricular myocardium. Using SDS-PAGE and Western blot we resolved three isoforms. The profiling of TnT did not differ significantly between the PIH-treated group and the Cremophor-treated group. Our data concerning cTnT support the opinion that the possible cardiotoxicity of PIH is very low.
Adamcová
M
M
Department of Physiology, Faculty of Medicine of Charles University, Hradec Kralove, Czech Republic. adamcova@lfhk.cuni.cz
Machácková
J
J
Gersl
V
V
Pelouch
V
V
Simůnek
T
T
Klimtová
I
I
Hrdina
R
R
Ponka
P
P
D000818:Animals; D002458:Cell Fractionation / Q000379:methods; D003600:Cytosol / Q000378:metabolism; D007502:Iron Chelating Agents / Q000633:toxicity*; D019190:Iron Overload / Q000188:drug therapy; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000633:toxicity*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism; D011730:Pyridoxal / Q000031:analogs & derivatives* / Q000633:toxicity*; D011817:Rabbits; D020107:Troponin T / Q000097:blood*
D007502:Iron Chelating Agents; D020107:Troponin T; D011730:Pyridoxal; C021079:pyridoxal isonicotinoyl hydrazone; D007538:Isoniazid