Responses of thiols to an oxidant challenge: differences between blood andtissues in the rat

Treatment of rats with diamide (100 mg/kg ip) altered the thiol components of the blood to a very different extent than in tissues (liver, kidney, lun g, spleen, heart and testis). A total consumption (10 min) and regeneration (120 min) of blood glutathione (GSH), matched by a parallel increase and d ecrease in glutathione-protein mixed disulfides (GS-SP) was observed. In co ntrast, no modification of non-protein SH groups (NPSH) and protein SH grou ps (PSH), GS-SP and malondialdehyde (MDA) was observed in liver, kidney, lu ng, testis spleen and heart within same time range. In particular, only glu tathione disulfide (GSSG) levels and some activities of antioxidant enzymes were modified to a small extent and in an opposite direction in some organ s. For example, GSSG, and glucose-6-phosphate dehydrogenase (G-6-PDH) and c atalase (CAT) activities appeared up-regulated in one tissue and down-regul ated in another. The least modified organ was the liver, whereas lung and s pleen were the most affected (lung, GSSG, significantly increased whereas G -6-PDH, glutaredoxin (GRX), GPX, superoxide dimutase (SOD) levels were sign ificantly lowered; spleen, GSSG and the activity of glutathione reductase ( GR), G-6-PDH and glutathione transferase (GST) were significantly decreased ). The different responses of erythrocytes and organs to diamide were expla ined by the high affinity of hemoglobin and by the relatively high potentia l of thiol regeneration in organs. The rapid reversibility of the process o f protein S-thiolation in blood and the small effects in organs leads us to propose the existence af an inter-organ cooperation in the rat that regula tes protein S-thiolation in blood. Plasma thiols may well play a role in th is process. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.