Comparative Evaluation of the Effects of Taurine and Thiotaurine on Alterations of the Cellular Redox Status and Activities of Antioxidant and Glutathione-Related Enzymes by Acetaminophen in the Rat - Advances in Experimental Medicine and Biology - page 192

10

200

Liver
Plasma

9

180

8

160

7

140

6

120

5 100

4

80

3

60

2

40

1

20

0

0

Control NAC TAU TTAU APAP NAC +

APAP

TAU +
APAP

TTAU +
APAP

Fig. 20.2 The effects of NAC, TAU, and TTAU on liver and plasma GSH levels of rats treated
with a hepatotoxic (800 mg/kg i.p.) dose of APAP. Differences were significant from control 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

Experiments in rodents have demonstrated that an acute high dose of APAP can
lower the hepatic GSH levels as early as 15 min after its administration (Lores Arnaiz
et al. 1995 ; Lauterburg et al. 1983 ). From the results presented in Fig. 20.2 , it is
apparent that APAP depleted GSH both in the liver (by 76%, p < 0.001) and plasma
(by 39%, p < 0.01), changes that were much less pronounced in the presence of TTAU
(+5% and −11%, respectively). By comparison, protection was less in the presence
of TAU (−20%, p < 0.01, and −46%, p < 0.001, respectively) and about equal follow-
ing a treatment with NAC (−10% and −2%, respectively) relative to TTAU.
The loss of GSH upon the administration of APAP has occurred concomitantly
with a proportional decrease in arterial plasma GSH concentration but not with a
corresponding increase in GSSG, findings that are consistent with the hypothesis
that the liver is a major source of plasma GSH (Adams et al. 1983 ) . In the present
study, APAP (800 mg/kg) lowered the GSSG levels in both plasma (−25%, p < 0.01)
and liver (−47%, p < 0.001) (Fig. 20.3 ), effects that were counteracted by TAU
(−19% and −22%, p < 0.05, respectively) and TTAU (−15%, p < 0.05, and +66%,
p < 0.001) relative to control values. NAC, on the other hand, was about equipotent
with TTAU (−14% and +46%, p < 0.001, respectively). In parallel with a decrease in
hepatic GSH and GSSG, there was also a corresponding decrease in the GSH/GSSG
ratio both in the plasma (−19%, p < 0.05) and liver (−54%, p < 0.001) (Fig. 20.4 ).
These changes were attenuated by TAU (−23% and −29%, respectively, both at
p < 0.05) and reversed by TTAU (+10% and 66%, p < 0.001, respectively) and NAC
(+4 and +46%, p < 0.001, respectively).