Modulation of rat erythrocyte antioxidant defense system by buthionine sulfoximine and its reversal by glutathione monoester therapy.
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.
Rajasekaran
Namakkal Surappan
NS
Unit of Biochemistry, Department of Zoology, University of Madras, Guindy Campus, Chennai, 600 025, India. nsrajachem@rediffmail.com
Devaraj
Niranjali S
NS
Devaraj
Halagowder
H
D000251:Adenosine Triphosphatases / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000378:metabolism*; D019328:Buthionine Sulfoximine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002374:Catalase / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000172:deficiency / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000097:blood; D006861:Hydrogen Peroxide; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008563:Membrane Lipids / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D010743:Phospholipids / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014810:Vitamin E / Q000097:blood
D000975:Antioxidants; D004791:Enzyme Inhibitors; D008563:Membrane Lipids; D010743:Phospholipids; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D008315:Malondialdehyde; D019328:Buthionine Sulfoximine; C042431:S-ethyl glutathione; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000251:Adenosine Triphosphatases; D005978:Glutathione