Novel synthesized aminosteroidal heterocycles intervention for inhibiting iron-induced oxidative stress.
The objective of this study was to elucidate the potential role of novel synthesized aminosteroidal heterocyclic compounds 2, 5, 9b and 10c against iron-induced oxidative stress with particular insight on erythrocyte ghosts in male rats. Chronic iron supplementation (3000 mg kg(-1) diet) for 6 weeks significantly increased plasma iron and ferritin levels. It also produced significant increase in plasma TNF-alpha and NO levels. Lipid metabolism was also affected by excess iron, so that plasma and erythrocyte membrane total cholesterol, triglycerides, phospholipids and total lipid levels were significantly elevated. In consequence, a significant increase in plasma leptin level was detected. Iron overload clearly induces oxidative stress as indicated by the significant increase in both plasma and erythrocyte membrane lipid peroxidation levels. Noteworthy, excess iron not only decreased the mean value of erythrocyte membrane protein but also caused marked alterations in the membrane protein fractions with concomitant inhibition in erythrocyte membrane ATPases activity. On the other hand, treatment with the aminosteriodal heterocyclic compounds especially compounds 5, 2, and 10c in an oral dose of 5 mg kg(-1) B.W. per day could ameliorate almost all of the changes in plasma and erythrocyte ghosts components induced by iron overload. The efficacious role of these novel synthesized aminosteriods in preventing iron-induced oxidative stress may be mediated through their iron chelating properties, anti-lipid peroxidation activities and membrane stabilizing actions. The encouraging results obtained in the present study lend credence to substantial investigation to assess the use of these compounds as a potent line of therapy to retard the pathogenesis of iron overload diseases.
Elmegeed
Gamal A
GA
Hormones Department, National Research Center, Dokki, Giza, Egypt. gamalae@hotmail.com
Ahmed
Hanaa H
HH
Hussein
Jihan S
JS
D000251:Adenosine Triphosphatases / Q000187:drug effects; D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D007501:Iron / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D019190:Iron Overload / Q000188:drug therapy* / Q000378:metabolism; D019266:Iron, Dietary; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D008968:Molecular Conformation; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013260:Steroids, Heterocyclic / Q000138:chemical synthesis / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D019266:Iron, Dietary; D008563:Membrane Lipids; D013260:Steroids, Heterocyclic; D007501:Iron; D000251:Adenosine Triphosphatases