Formoterol fumarate and roxithromycin effects on muscle mass in an animal model of cancer cachexia.
Our study probed the effects of the beta-2 adrenergic agonist, formoterol and the macrolide antibiotic, roxithromycin, on muscle wasting in a well-characterized animal model of cancer cachexia. Female Wistar rats were inoculated with Yoshida AH130 ascites hepatoma (AH) cells to induce rapid and severe cachexia as demonstrated by wet weight determinations of the hearts, gastrocnemius muscles and carcasses. The control animals received saline (vehicle) inoculations. The AH-inoculated rats were treated once daily for four days by i.p. injection with a vehicle control, 1 mg/kg formoterol, 5 and 50 mg/kg roxithromycin or 1 mg/kg formoterol plus 5, 25, 40 and 50 mg/kg roxithromycin. The saline-inoculated animals were treated by i.p. injection with vehicle control, 1 mg/kg formoterol, 5 and 40 mg/kg roxithromycin. As a result, formoterol alone reduced the loss of muscle mass in the AH-inoculated rats by approximately one-half, consistent with literature reports. Roxithromycin alone at 5 mg/kg did not affect muscle mass in the AH-inoculated rats. Roxithromycin given alone at 50 mg/kg reduced the loss of muscle mass in AH-inoculated animals by approximately one-half. With respect to the antagonizing muscle loss, formoterol combined with either 5 or 25 mg/kg roxithromycin did not reach statistical significance versus formoterol alone, while formoterol plus either 40 or 50 mg/kg roxithromycin enhanced protection against muscle loss versus formoterol alone. The gastrocnemius weights in the AH-inoculated rats treated with formoterol combined with 40 mg/kg roxithromycin were not significantly different from the muscle weights in the saline-inoculated controls. To sum up, formoterol and roxithromycin apparently exert anti-cachectic effects in an additive fashion and may offer the potential for combination therapy in cachexia.
Kenley
Richard A
RA
Anaborex, Inc., La Jolla, CA 92037, USA. rkenley@anaborex.com
Denissenko
Mikhail F
MF
Mullin
Robert J
RJ
Story
Jennifer
J
Ekblom
Jonas
J
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002100:Cachexia; D006528:Carcinoma, Hepatocellular / Q000628:therapy; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D000068759:Formoterol Fumarate; D015233:Models, Statistical; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009132:Muscles / Q000187:drug effects*; D009133:Muscular Atrophy / Q000188:drug therapy*; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D015575:Roxithromycin / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000900:Anti-Bacterial Agents; D004983:Ethanolamines; D015575:Roxithromycin; D000068759:Formoterol Fumarate