mitochondrial antioxidant pattern in livers from rats

31° Congresso Nazionale della Società Italiana di Farmacologia
Trieste, 26-29 giugno 2003
MITOCHONDRIAL ANTIOXIDANT PATTERN IN LIVERS FROM RATS AFTER
LONG-TERM TREATMENT WITH CYCLOSPORINE A
Bompadre S.*, Pugnaloni A.#, Politi A.*, Rubini C.**, Ferreiro M.S.°, Gallardo I.°°, Bullon
P.°°, Battino M.§
*Institute of Microbiology and Biomedical Sciences, §Institute of Biochemistry, #Institute of
Human Morphology, **Istituto di Anatomia Patologica, °Institute of Infective Diseases and
Public Health, Università politecnica delle Marche, Ancona ITALY
°°Departamento de Estomatologia, Universidad de Sevilla, SPAIN
CyclosporineA (CyA) is widely used as the immunosuppressant, however, its use is often
associated with hepatic and renal side effects observed in humans and rats. It prevents the
mitochondrial permeability transition pore opening . Since the modulation of permeability
transition is dependent by many positive and negative effectors, including the different redox
forms of some antioxidants, we decided to investigate if a long-term treatment with CyA may
have any effects on the lipophilic and hydrophobic antioxidant pattern of rat liver
mitochondria. 20 Wistar rats were treated i.p. for 4 weeks with CyA (30 mg/Kg/day) or with
the CyA vehicle 24 hours after their last injection animal were anaesthetized and killed. Liver
mithocondria were obtained by differential centrifugation. Quantitative measurement of
mitochondrial antioxidant contents was performed with HPLC. As far as the lipophilic
antioxidants (Vit. E, CoQ9 and CoQ10) are concerned, CyA treated rats are characterized by
higher antioxidant concentrations.This difference occurs in all cases altough the variability of
data is particularly high in the samples proceeding from CyA treated rats. More than 60% of
CoQ9 and more than 80% of CoQ10 result in reduced form and the CoQ9/CoQ10 ratio is
slightly more than 10 and remain constant regardless CyA administration. Hydrophilic
antioxidants reveal contrasting results:in fact glutathione is higher in CyA treated rats,uric acid
is similar in both treated and untreated and finally ascorbic acid is higher in the control
group.However, the differences are not statistically significant because values from CyA
treated present a great variability. These preliminar evidence seems to suggest that CyA does
not affects the redox status of antoxidants investigated despite the various morphofunctional
effects produced by CyA.
Antioxidants in liver mithocondria: Control (Ctrl) CyA treated rats. Mean ± SEM nmol/mg
N=10 Q9ox
Q9red
Q10ox
Q10red
Vit E
GSH
Uric A. Ascorbic A.
Ctrl 0.77±0.08 2.11±0.28 0.04±0.02 0.17±0.03 450±60 4.61±0.59 0.04±0.01 0.79±0.31
CyA 0.82±0.23 2.99±1.04 0.02±0.02 0.28±0.07 530±130 7.81±1.39 0.05±0.00 0.44±0.12
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