e n v i r o n m e n t a l t o x i c o l o g y a n d p h a r m a c o l o g y 3 6 ( 2 0 1 3 ) 296–302
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The effect of calorie restriction on acute ethanol-induced
oxidative and nitrosative liver injury in rats
Duˇ san Mladenovi´ c
a
, Milica Ninkovi´ c
b
, Vuk Aleksi´ c
a
, Tamara
ˇ
Sljivanˇ canin
c
,
Danijela Vuˇ cevi´ c
a
, Vera Todorovi´ c
d
, Milena Stankovi´ c
a
, Olivera Stanojlovi´ c
e
,
Tatjana Radosavljevi´ c
a,*
a
Institute of Pathophysiology, “Ljubodrag Buba Mihailovi´ c”, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
b
Institute for Medical Research, Military Medical Academy, Belgrade, Serbia
c
Clinics of Gynecology and Obstetrics, “Narodni front”, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
d
Faculty of Dentistry,Panˇ cevo, University of Business Economy, Novi Sad, Serbia
e
Institute of Medical Physiology, “Richard Burian”, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
a r t i c l e i n f o
Article history:
Received 17 October 2012
Received in revised form
9 April 2013
Accepted 10 April 2013
Available online 17 April 2013
Keywords:
Calorie restriction
Liver
Oxidative stress
Ethanol
Rats
a b s t r a c t
The aim of our study was to examine the effect of calorie restriction (CR) on oxidative and
nitrosative liver injury in rats, induced by acute ethanol intoxication. Male Wistar rats were
divided into groups: (1) control; (2) calorie-restricted groups with intake of 60–70% (CR
60–70
)
and 40–50% of daily energy needs (CR
40–50
); (3) ethanol-treated group (E); (4) calorie-restricted,
ethanol-treated groups (E + CR
60–70
and E + CR
40–50
). Ethanol was administered in 5 doses of
2 g/kg every 12 h, and duration of CR was 5 weeks before ethanol treatment. Malondialdehyde
and nitrite and nitrate level were significantly lower in E + CR
60–70
and higher in E + CR
40–50
vs.
E group. Liver reduced glutathione content and activity of both superoxide dismutase izoen-
zymes were significantly higher in E + CR
60–70
and lower in E + CR
40–50
vs. E group. Oxidative
stress may be a potential mechanism of hormetic effects of CR on acute ethanol-induced
liver injury.
© 2013 Elsevier B.V. All rights reserved.
1. Introduction
Calorie restriction (CR) is a well known procedure that extends
the lifespan of a wide variety of organisms, and reduces the
incidence of many diseases, such as malignancy, diabetes,
obesity, autoimmune diseases, sarcopenia, etc. (Martin et al.,
2006; Weindruch, 1996). The mechanisms of beneficial effects
of CR are not completely understood. CR-induced increase in
SIRT1 expression is known to be an important mechanism of
lifespan prolongation and prevention of aging-related cogni-
tive impairment and neurodegeneration (Corbi et al., 2012).
∗
Corresponding author. Tel.: +381 11 2685 340; fax: +381 11 2685 340.
E-mail address: tanjamm@med.bg.ac.rs (T. Radosavljevi´ c).
Potential additional mechanisms of beneficial effects of CR
include: metabolic and neuroendocrine changes (Koukova and
Guarente, 2003), modification of the expression of numerous
genes (Lee et al., 1999), decrease in glycosylation rate of the
macromolecules (Sell et al., 1996) and reduction of serum con-
centrations of several growth factors (platelet-derived growth
factor/PDGF/, transforming growth factor-beta/TGF-/) and
fasting insulin level. Long-term CR with adequate vitamin and
micronutrient intake is associated with decreased serum tri-
iodothyronine concentration, which may, also, contribute to
delay of biological aging in humans (Koukova and Guarente,
2003).
1382-6689/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.etap.2013.04.002