Short-term effects of thalidomide analogs on hepatic glycogen and nitric oxide in endotoxin-challenged rats.
Hepatic glycogen metabolism is altered by nitric oxide (NO) during endotoxic shock. Thalidomide analogs immunomodulate the endotoxin-induced cytokines which regulate the NO release. We analyzed the short-term effects of some thalidomide analogs on the hepatic glycogen store and on the plasma and hepatic NO in an acute model of endotoxic challenge in rat. An endotoxin dose selection was performed. Rats received vehicle, thalidomide or analogs orally and, two hours after last dose, they were injected with endotoxin (5 mg/kg). Animals were sacrificed 2 h after challenge. Liver glycogen was quantified by the anthrone technique. Plasma and hepatic NO was determined by Griess reagent and HPLC. Hepatic interferon-gamma, a NO co-inducer, was measured by ELISA. Endotoxin caused inverse dose-dependent effects on plasma NO and on glycogen.Thalidomide analogs showed short-term regulatory effects on glycogen, some of them increased it. Plasma NO was almost unaffected by analogs but hepatic NO was strikingly modulated. Analogs slightly up-regulated the liver interferon-gamma and two of them increased it significantly. Thalidomide analogs may be used as a pharmacological tool due to their short-term regulatory effects on glycogen and NO during endotoxic shock. Drugs that increase glycogen may improve liver injury in early sepsis.
Fernández-Martínez
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E
Centro de Investigación en Biología de la Reproducción, Area Académica de Medicina, I.C.Sa.-Universidad Autónoma del Estado de Hidalgo, Hidalgo, Mexico. efernan@uaeh.reduaeh.mx
Wens-Flores
I
I
Moreno
M G
MG
Ortiz
M I
MI
Muriel
P
P
Pérez-Alvarez
V
V
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000633:toxicity*; D006003:Glycogen / Q000378:metabolism*; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013997:Time Factors
D004731:Endotoxins; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D013792:Thalidomide; D007371:Interferon-gamma; D006003:Glycogen