Role for glutathione in the hyposensitivity of LPS-pretreated mice to LPS anorexia.
To study the role of the redox state regulator glutathione (GSH) in bacterial lipopolysaccharide (LPS)-induced anorexia we measured total reduced GSH (trGSH) in liver, serum and brain in response to intraperitoneal (ip) lipopolysaccharide (LPS, 4 microg/mouse) injection in LPS-naïve and LPS-pretreated (4 microg/mouse given 3 days earlier) mice. LPS reduced food intake in LPS-naïve mice and LPS pretreatment attenuated this effect. LPS decreased trGSH at 24 hours after injection in LPS-naïve mice but 4 days later trGSH levels were upregulated in brain and liver, and this was associated with a significant attenuation of LPS-induced anorexia. In addition, LPS increased mitochondrial GSH levels in brain and liver at 4 days after injection. Pharmacological GSH depletion with diethylmaleate and L-buthionine sulfoximine in LPS-pretreated mice ablated the hyposensitivity to the anorexic effect of LPS. Together, these findings suggest a prominent role for GSH and its intracellular repartition in LPS anorexia.
Hernadfalvi
Noemi
N
Institute of Animal Sciences, ETH Zurich, Schwerzenbach, Switzerland.
Langhans
Wolfgang
W
von Meyenburg
Claudia
C
Onteniente
Brigitte
B
Richard
Denis
D
Arsenijevic
Denis
D
D000818:Animals; D000855:Anorexia / Q000378:metabolism*; D019328:Buthionine Sulfoximine / Q000737:chemistry; D005978:Glutathione / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D008298:Maleates / Q000494:pharmacology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008070:Lipopolysaccharides; D008298:Maleates; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D019328:Buthionine Sulfoximine; D007371:Interferon-gamma; C014476:diethyl maleate; D005978:Glutathione