| A groups of sulfur-containing compounds consisting of S-substituted analogs of L-cysteine (5-allyl-, S-ethyl-, S-propyl-) and analogs (acetyltaurine = ATAU, methyltaurine = MTAU, pantoyltaurine = PTAU), homologs (homotaurine = HMTAU) and oxidation products (hypotaurine = HYTAU, thiotaurine = THTAU) of taurine (TAU) were compared with each other and with N-acetylcysteine (NAC) and TAU, serving as reference compounds, for the ability to protect the liver and kidney against acetaminophen (APAP)-induced toxicity. For this purpose, Sprague-Dawley rats were intraperitoneally (i.p.) dosed with APAP (800 mg/kg), with or without an i.p. treatment with a sulfur-containing compound (2.4 mmol/kg), given 30 min earlier. In addition, rats were also pretreated with NAC plus TAU. After sacrificing the animals at 6 hr post APAP, blood, liver and kidney samples were collected for the assay of indicators of cellular damage (aspartate and alanine transaminases = ALT and AST, lactate dehydrogenase = LDH), oxidative stress (malondialdehyde = MDA, reduced and oxidized glutathione = GSH and GSSG, catalase = CAT, glutathione peroxidase = GPX, superoxide dismutase = SOD), GSH utilization (glutathione S-transferase = GST), synthesis (gamma-glutamylcysteinyl synthase = GCS) and recycling (glutathione reductase = GR). In addition, the liver was evaluated for APAP-protein adduct formation, and liver and kidney samples were submitted to histological examination. In comparison to results for saline-treated rats serving as controls, APAP significantly (p≤0.05) elevated the values of circulating AST, ALT and LDH and of intracellular and circulating MDA, and lowered the intracellular and circulating values of GSH, GSSG, CAT, GPX, SOD, GST, GCS and GR, more so in the liver than in the kidney. All the treatment compounds were able to counteract APAP-induced biochemical alterations, with the magnitude of the effect varying from compound to compound and from test to test. Among L-cysteine analogs, the protective actions generally decreased in the order S-propyl ≥ NAC > S-ethyl > S-allyl. Among TAU-related compounds, HYTAU, THTAU, HMTAU, and PTAU, in that order, were usually the most protective, ATAU and MTAU the least, and, often, HYTAU and THTAU were better than NAC. Whereas TAU was less potent than NAC in all tests but those for antioxidant enzymes and GR, their combined administration led, in most instances, to a greater protection that when given separately. APAP-adduct formation was only detected in rats receiving APAP and APAP-MTAU, and histological abnormalities, consisting of centrilobular necrosis, cellular enlargement, sinusoidal vacuolation and infiltration by macrophages, were absent in all kidney samples and only observed in the livers of rats on APAP, APAP-ATAU and APAP-MTAU. |
