title: Anti-TNF treatment reduces rat skeletal muscle wasting in monocrotaline-induced cardiac cachexia.
abstract: The aim was to explore efficacy of tumor necrosis factor (TNF) inhibitors in attenuating increases in anorexia and ubiquitin proteasome pathway transcripts in cardiac cachexia, a potentially lethal condition that responds poorly to current treatments. Cardiac cachexia was rapidly induced with monocrotaline in Sprague-Dawley rats. Either soluble TNF receptor-1 or the general inhibitor of TNF production, pentoxifylline, was given to diminish TNF action on the first indication of cachexia. Animals were anesthetized with a ketamine-xylazine-acepromazine cocktail, and then skeletal muscles were removed for subsequent measurements including ubiquitin proteasome pathway transcripts and Western blots. Both soluble TNF receptor-1 and pentoxifylline attenuated losses in both body and skeletal muscle masses and also reduced increases in selected ubiquitin proteasome pathway transcripts. The action of soluble TNF receptor-1 was partly through reversal of reduced food consumption, while the effects of pentoxifylline were independent of food intake. Here we demonstrate, for the first time, that attenuation of anorexia by soluble TNF receptor-1 treatment in monocrotaline-induced cardiac cachexia is responsible for attenuating increases in some ubiquitin proteasome pathway transcripts as well as preserving body mass and attenuating loss of skeletal muscle mass.
authors.affiliation: Department of Medical Pharmacology, Dalton Cardiovascular Institute, University of Missouri, Columbia, Missouri 65211, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Steffen
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Lees
authors.forename: Frank W
authors.initials: FW
authors.lastname: Booth
mesh_terms: D000818:Animals; D000855:Anorexia / Q000188:drug therapy / Q000209:etiology; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000139:chemically induced* / Q000150:complications / Q000473:pathology*; D004435:Eating / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology*; D008297:Male; D016686:Monocrotaline; D018482:Muscle, Skeletal / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D010431:Pentoxifylline / Q000031:analogs & derivatives / Q000494:pharmacology; D011042:Poisons; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000079424:Tumor Necrosis Factor Inhibitors; D025801:Ubiquitin / Q000502:physiology; D015431:Weight Loss / Q000187:drug effects
chemical_list: D011042:Poisons; D047888:Receptors, Tumor Necrosis Factor, Type I; D000079424:Tumor Necrosis Factor Inhibitors; D025801:Ubiquitin; D012313:RNA; C061298:torbafylline; D016686:Monocrotaline; D010431:Pentoxifylline