PMID- 14990342 OWN - NLM STAT- MEDLINE DCOM- 20040423 LR - 20161126 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1688 IP - 2 DP - 2004 Mar 2 TI - Modulation of rat erythrocyte antioxidant defense system by buthionine sulfoximine and its reversal by glutathione monoester therapy. PG - 121-9 AB - The protective effects of glutathione monoester (GME) on buthionine sulfoximine (BSO)-induced glutathione (GSH) depletion and its sequel were evaluated in rat erythrocyte/erythrocyte membrane. Animals were divided into three groups (n=6 in each): control, BSO and BSO+GME group. Administration of BSO, at a concentration of 4 mmol/kg bw, to the albino rats resulted in depletion of blood GSH level to about 59%. GSH was elevated several folds in the GME group as compared to the control (P<0.05) and BSO (P<0.001) groups. Decreased concentration of vitamin E was found in the erythrocyte membrane isolated from BSO-administered animals. Antioxidant enzymes, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) were also found to be altered due to BSO-induced GSH depletion in blood erythrocytes. The SOD and CAT activities in BSO group were significantly lower (P<0.001) than the other groups. Lipid peroxidation index and malondialdehyde (MDA) levels in erythrocytes and their membranes were increased to about 45% and 40%, respectively. The activities of Ca2+ ATPase, Mg2+ ATPase and Na+K+ ATPase were lower than those of control group (P<0.05), whereas the activities of these enzymes were found to be restored to normal followed by GME therapy (P<0.05). Cholesterol, phospholipid and C/P ratio and some of the phospholipid classes like phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphingomyelin were significantly (P<0.05) altered in the erythrocyte membranes of BSO-administered rats compared with those of control group. These parameters were restored to control group levels in GME-treated group. Oxidative stress may play a major role in the BSO-mediated gamma glutamyl cysteine synthetase (gamma-GCS) inhibition and hence the depletion of GSH. In conclusion, our findings have shown that antioxidant status decreased and lipid peroxidation increased in BSO-treated rats. GME potentiates the RBC and blood antioxidant defense mechanisms and decreases lipid peroxidation. FAU - Rajasekaran, Namakkal Surappan AU - Rajasekaran NS AD - Unit of Biochemistry, Department of Zoology, University of Madras, Guindy Campus, Chennai, 600 025, India. nsrajachem@rediffmail.com FAU - Devaraj, Niranjali S AU - Devaraj NS FAU - Devaraj, Halagowder AU - Devaraj H LA - eng PT - Comparative Study PT - Journal Article PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (Antioxidants) RN - 0 (Enzyme Inhibitors) RN - 0 (Membrane Lipids) RN - 0 (Phospholipids) RN - 0 (Thiobarbituric Acid Reactive Substances) RN - 1406-18-4 (Vitamin E) RN - 4Y8F71G49Q (Malondialdehyde) RN - 5072-26-4 (Buthionine Sulfoximine) RN - 7W95D60F4J (S-ethyl glutathione) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.11.1.6 (Catalase) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 3.6.1.- (Adenosine Triphosphatases) RN - GAN16C9B8O (Glutathione) SB - IM MH - Adenosine Triphosphatases/blood MH - Animals MH - Antioxidants/analysis/*metabolism MH - Buthionine Sulfoximine/administration & dosage/antagonists & inhibitors/*pharmacology MH - Catalase/blood MH - Chromatography, High Pressure Liquid MH - Enzyme Inhibitors/pharmacology MH - Erythrocyte Membrane/drug effects/metabolism MH - Erythrocytes/*drug effects/metabolism MH - Glutathione/*analogs & derivatives/deficiency/*therapeutic use MH - Glutathione Peroxidase/blood MH - Hydrogen Peroxide MH - Lipid Peroxidation MH - Male MH - Malondialdehyde/blood MH - Membrane Lipids/blood MH - Oxidative Stress/drug effects MH - Phospholipids/blood MH - Rats MH - Rats, Wistar MH - Superoxide Dismutase/blood MH - Thiobarbituric Acid Reactive Substances/analysis MH - Vitamin E/blood EDAT- 2004/03/03 05:00 MHDA- 2004/04/24 05:00 CRDT- 2004/03/03 05:00 PHST- 2003/09/09 00:00 [received] PHST- 2003/11/07 00:00 [revised] PHST- 2003/11/11 00:00 [accepted] PHST- 2004/03/03 05:00 [pubmed] PHST- 2004/04/24 05:00 [medline] PHST- 2004/03/03 05:00 [entrez] AID - S0925443903001911 [pii] AID - 10.1016/j.bbadis.2003.11.004 [doi] PST - ppublish SO - Biochim Biophys Acta. 2004 Mar 2;1688(2):121-9. doi: 10.1016/j.bbadis.2003.11.004.