Biology Reference
In-Depth Information
80
Liver
Plasma
70
14
60
12
50
10
8
40
6
30
4
20
2
10
0
0
Control
NAC
TAU
TTAU
APAP
NAC +
APAP
TAU +
APAP
TTAU +
APAP
Fig. 20.5 The effects of NAC, TAU, and TTAU on the activities of liver and plasma CAT of rats
treated with a hepatotoxic (800 mg/kg i.p.) dose of APAP. Differences were significant from con-
trol at * p < 0.05, ** p < 0.01, and *** p < 0.001 and from APAP at †† p <0.01 and ††† p < 0.001. Values
are shown as mean ± SEM for n = 6
At high doses APAP can make the liver more vulnerable to the deleterious effects
of oxidative stress through its inhibitory interaction with antioxidant enzymes
known to interact and destroy specific ROS (Matés 2000 ). In agreement with the
results reported by other investigators in rats (Sabina et al. 2009 ) and mice (Olaleye
and Rocha 2008 ), this work verified that the activity of CAT and SOD was decreased
by a high dose of APAP both in the plasma and liver. This situation will certainly
add to the susceptibility of liver cells to oxidative stress inasmuch as each of these
enzymes is involved in ROS detoxification (hydrogen peroxide by CAT, hydrogen
peroxide and other peroxides by GPx, superoxide anion by SOD). As seen in
Figs. 20.5 and 20.6 , the plasma activities of these enzymes were reduced by 56%
and 29%, respectively, relative to control values ( p £ 0.01) and by 41% and 58%,
respectively ( p £ 0.01), in the liver. All the pretreatment compounds were able to
prevent the losses in antioxidant enzyme activities to a significant extent in the
plasma (CAT by only 1-11%, SOD by ~11%) and liver (CAT 7-15%, SOD by
26-35%, p < 0.01), with TAU providing a nonsignificantly greater protection than
either TTAU or NAC. While the activity of CAT may protect against LPO by
preventing iron-catalyzed generation of ROS, an increase in SOD activity may cur-
tail the accumulation of MDA in parallel with liver necrosis (Nakae et al. 1990 ) .
In vitro studies in which isolated rat hepatocytes were exposed to an oxidant in the
presence and absence of inhibitors of GPx and GR have suggested that the GPx/GR
system can protect hepatocytes from damage by oxidative stress and can decrease
 
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