Protection against dextran sodium sulfate-induced colitis by dehydroepiandrosterone and 7alpha-hydroxy-dehydroepiandrosterone in the rat.
In this study the anti-oxidant effect of DHEA and 7alpha-hydroxy-DHEA against oxidative stress induced by colitis was investigated in vivo in rats. The two steroids were intraperitoneally injected once daily (50 mg/kg body weight) for 7 days before the induction of colitis that was effected by a daily treatment of 5% (w/v) dextran sodium sulfate (DSS) in drinking water for 7 days. This was quantified by the evidence of weight loss, rectal bleeding, increased wall thickness, and colon length. The inflammatory response was assessed by neutrophil infiltration after a histological examination and myeloperoxidase (MPO) activity measurement. Two markers of oxidative damage were measured in colon homogenates after the onset of DSS treatment: protein carbonyls and thiobarbituric acid-reacting substances. The colonic metabolism of corticosterone by 11beta-hydroxysteroid dehydrogenases types 1 and 2 (11beta-HSD) was investigated in control and treated animals. Results indicated that colitis caused a decrease in body weight and colon length. Severe lesions were observed in the colon with a reduced number of goblet cells which contained less mucins. The lesions were associated with increased MPO activity and oxidative damage. Colonic inflammation down and up regulated the 11beta-HSD2 and 11beta-HSD1, respectively. Treatments by DHEA and 7alpha-hydroxy-DHEA attenuated the inflammatory response when MPO activity decreased; but this did not increase the colonic oxidation of corticosterone into 11-dehydrocorticosterone. Both DHEA and 7alpha-hydroxy-DHEA exerted a significant anti-oxidant effect against oxidative stress induced by colitis through reducing the oxidative damage to proteins and lipids. This resulted in a moderate increase in the amount of colonic mucus. Both DHEA and 7alpha-hydroxy-DHEA may prove useful in the prevention or treatment of colitis.
Pélissier
Marie-Agnès
MA
Laboratoire de Biologie, EA-3199, Conservatoire National des Arts et Métiers, 2 rue Conté, 75003 Paris, France.
Muller
Caroline
C
Hill
Martin
M
Morfin
Robert
R
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016264:Dextran Sulfate / Q000633:toxicity*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects
D000276:Adjuvants, Immunologic; D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D003687:Dehydroepiandrosterone; C003587:7-hydroxydehydroepiandrosterone; D016264:Dextran Sulfate; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D009195:Peroxidase