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 188

glutathione redox cycling, transfer, and synthesis in the rat (Acharya and Lau-Cam
2010 ). The rationale for testing these sulfur-containing compounds as protection
against APAP hepatotoxicity stemmed from previous recognition that TAU was
capable of attenuating LPO, apoptosis, necrosis, and DNA fragmentation in hepato-
cytes from rats treated with a toxic dose of APAP (Waters et al. 2001 ) and that TAU
and HYTAU effectively lowered LPO, the fall of the GSH/GSSG ratio, and the loss
of antioxidant enzyme activities in erythrocytes from diabetic rats (Gossai and Lau-
Cam 2009 ). Since these results pointed to a determining role for the sulfur-containing
functionality in the potency differences noted in erythrocytes between TAU and
HYTAU, the present study was undertaken to further validate this assumption by
comparing the actions of TAU in APAP-related hepatotoxicity against those of thio-
taurine (TTAU), the thiosulfonate (-SO 2 -SH) analog thiotaurine which has also been
found to possess antioxidant actions (Egawa et al. 1999 ; Yoshiyuki 1998 ; Yoshiyuki
and Yoshiki 2000 ).To better define the degree of protective action of TAU and
TTAU in APAP-induced hepatotoxicity, their activities were compared against those
of NAC.

20.2 Methods

20.2.1 Chemicals

The chemicals used in the present study were obtained from commercial sources in
the USA. NAC, APAP, and chemicals used in the preparation of the biological sam-
ples and in the biochemical assays were purchased from Sigma-Aldrich, St. Louis,
MO. TTAU was from Wako Chemicals USA, Inc., Richmond, VA.

20.2.2 Animals, Treatments, and Sample Collections

Male Sprague-Dawley rats, weighing 200-250 g, were obtained from Taconic,
Germantown, New York, USA. The study received the approval of the Institutional
Animal Care and Use Committee of St. John's University, Jamaica, New York, and
the animals were cared in accordance with guidelines established by the United
States Department of Agriculture. The experimental groups consisted of six rats
each and they were used in the nonfasted state. The treatment solutions were pre-
pared just prior to an experiment. The APAP solution was made in warm 50% poly-
ethylene glycol (PEG) 400 and allowed to cool to ambient temperature before its
administration. The test compounds (NAC, TAU, TTAU) were dissolved in distilled
water. A treatment compound was administered as a single, 2.4 mmol/kg/2 mL,
dose 30 min before a hepatotoxic, 800 mg/kg/2 mL, dose of APAP. Animals serving
as controls only received 50% PEG 400 in a volume equal to 2 mL. All treatments