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

Abstract

The present study was carried out to ascertain the impact of replacing the sulfonate group of TAU with thiosulfonate, as present in thiotaurine (TTAU), on the protective actions of TAU against hepatocellular damage and biochemical alterations related to oxidative stress and glutathione redox cycling, synthesis, and utilization caused by a high dose of acetaminophen (APAP). To this end, male Sprague-Dawley rats, 225-250 g, were intraperitoneally treated with a 2.4 mmol/kg dose of TAU (or TTAU), followed 30 min later by 800 mg/kg of APAP. A reference group received 2.4 mmol/kg of N-acetylcysteine (NAC) prior to APAP. Naive rats served as controls. The animals were sacrificed 6 h after receiving APAP and their blood and livers were collected. Plasma and liver homogenates were analyzed for indices of cell damage (plasma transaminases, plasma lactate dehydrogenase), -oxidative stress (malondialdehyde = MDA, reduced glutathione = GSH, glutathione disulfide = GSSG, catalase, glutathione peroxidase, superoxide dismutase), glutathione cycling (glutathione reductase), utilization (glutathione S-transferase), and synthesis (γ-glutamylcysteine synthetase) activities. APAP increased MDA formation and lowered the GSH/GSSG ratio and all enzyme activities, especially those of antioxidant enzymes. In general, TTAU was equipotent with NAC and more potent than TAU in protecting the liver. Taken into account the results of a previous study comparing the actions of TAU and hypotaurine (HTAU), the sulfinate analog of TAU, it appears that the sulfinate and thiosulfonate analogs are somewhat more effective than the parent sulfonate TAU in counteracting APAP-induced hepatic alterations in the liver and plasma.

Protective role of taurine against oxidative stress (Review)

“…In addition to depleting intrahepatic GSH, APAP seems to decrease the activity of anti-oxidant enzymes (SOD, CAT, GPx), as well as of enzymes involved in glutathione redox cycling (glutathione reductase, GR), utilization (glutathione S-transferase, GST) and synthesis (gamma-glutamylcysteine synthetase) ( 237 ). In this context, taurine has been shown to improve the effects of APAP on both oxidative stress and glutathione redox metabolism ( 238 ). Taurine administered at a dose of 2.4 mmol/kg for 30 min following administration of 800 mg/kg APAP appeared to successfully alleviate both DNA damage signals and oxidative indices ( 238 ).…”

“…In this context, taurine has been shown to improve the effects of APAP on both oxidative stress and glutathione redox metabolism ( 238 ). Taurine administered at a dose of 2.4 mmol/kg for 30 min following administration of 800 mg/kg APAP appeared to successfully alleviate both DNA damage signals and oxidative indices ( 238 ). This was achieved by i) reducing MDA formation, ii) regulating glutathione cycling-utilization-synthesis cycle, iii) increasing the already reduced glutathione to glutathione disulfide (GSH/GSSG) ratio and iv) increasing the activity of all anti-oxidant enzymes ( 238 ).…”

“…Taurine administered at a dose of 2.4 mmol/kg for 30 min following administration of 800 mg/kg APAP appeared to successfully alleviate both DNA damage signals and oxidative indices ( 238 ). This was achieved by i) reducing MDA formation, ii) regulating glutathione cycling-utilization-synthesis cycle, iii) increasing the already reduced glutathione to glutathione disulfide (GSH/GSSG) ratio and iv) increasing the activity of all anti-oxidant enzymes ( 238 ). Notably, hepatic damage mediated by paracetamol intake can be monitored through plasma and urine taurine levels ( 239 ).…”

Sulfane sulfur – new findings on an old topic

“…Thiotaurine possesses antioxidant and regulatory properties. Interestingly, a previous study had shown that the protective, antioxidant action of thiotaurine was stronger than that of taurine (Acharya & Lau-Cam, 2013). It was probably connected with presence of a thiosulfonate group in thiotaurine.…”

A preclinical study to model taurine pharmokinetics in the undernourished rat

“…Thus far, little is known about the pharmacokinetics of taurine after oral administration. Such information is essential if a regimen for administration of this agent as a nutraceutic in enteral diets or as therapeutic substance is designed – for example in treating the adverse effects of nickel in the nervous system ( 23 ) or after paracetamol poisoning ( 24 , 25 ) . A review of the literature revealed only very few reports concerning the pharmacokinetics of taurine.…”