Lack of Synergy Between β-Agonist Treatment and a Blockage of Sarcoplasmic Calcium Flow in a Rat Cancer Cachexia Model.
calcium
cancer cachexia
dantrolene
formoterol
ryanodine receptor 1
skeletal muscle
Journal
OncoTargets and therapy
ISSN: 1178-6930
Titre abrégé: Onco Targets Ther
Pays: New Zealand
ID NLM: 101514322
Informations de publication
Date de publication:
2021
2021
Historique:
received:
12
12
2020
accepted:
05
02
2021
entrez:
25
3
2021
pubmed:
26
3
2021
medline:
26
3
2021
Statut:
epublish
Résumé
During cancer cachexia, both skeletal muscle and adipose tissue losses take place. The use of β2-agonists, formoterol in particular, has proven to be very successful in the treatment of the syndrome in pre-clinical models. The object of the present research was to study the effects of a combination of formoterol and dantrolene, an inhibitor of the ryanodine receptor 1 (RyR1), on body weight loss and cachexia in tumour-bearing animals. Rats were separated into two groups: controls (C) and tumour bearing (TB). TB group was further subdivided into four groups: untreated (saline as a vehicle), treated with Formoterol (TF) (0,3 mg/kg body weight in saline, subcutaneous (s.c.), daily), treated with Dantrolene (TD) (5 mg/kg body weight in saline, subcutaneous (s.c.), daily), and double-treated treated (TFD) with Formoterol (0,3 mg/kg body weight, subcutaneous (s.c.), daily) and Dantrolene (5 mg/kg body weight, subcutaneous (s.c.), daily). 7 days after tumour transplantation, muscle weight, grip force, and total physical activity were specified in all experimental groups. While formoterol had, as in previous studies, a very positive effect in reducing muscle weight loss, dantrolene had no effects, neither on skeletal muscle nor on any of the parameters studied. Finally, the combined treatment (formoterol and dantrolene) did not result in any significant benefit on the action of the β2-agonist. It is concluded that, in the preclinical cachectic model used, no synergy exists between β2-agonist treatment and the blockade of sarcoplasmic-calcium flow.
Sections du résumé
BACKGROUND
BACKGROUND
During cancer cachexia, both skeletal muscle and adipose tissue losses take place. The use of β2-agonists, formoterol in particular, has proven to be very successful in the treatment of the syndrome in pre-clinical models. The object of the present research was to study the effects of a combination of formoterol and dantrolene, an inhibitor of the ryanodine receptor 1 (RyR1), on body weight loss and cachexia in tumour-bearing animals.
METHODS
METHODS
Rats were separated into two groups: controls (C) and tumour bearing (TB). TB group was further subdivided into four groups: untreated (saline as a vehicle), treated with Formoterol (TF) (0,3 mg/kg body weight in saline, subcutaneous (s.c.), daily), treated with Dantrolene (TD) (5 mg/kg body weight in saline, subcutaneous (s.c.), daily), and double-treated treated (TFD) with Formoterol (0,3 mg/kg body weight, subcutaneous (s.c.), daily) and Dantrolene (5 mg/kg body weight, subcutaneous (s.c.), daily). 7 days after tumour transplantation, muscle weight, grip force, and total physical activity were specified in all experimental groups.
RESULTS
RESULTS
While formoterol had, as in previous studies, a very positive effect in reducing muscle weight loss, dantrolene had no effects, neither on skeletal muscle nor on any of the parameters studied. Finally, the combined treatment (formoterol and dantrolene) did not result in any significant benefit on the action of the β2-agonist.
CONCLUSION
CONCLUSIONS
It is concluded that, in the preclinical cachectic model used, no synergy exists between β2-agonist treatment and the blockade of sarcoplasmic-calcium flow.
Identifiants
pubmed: 33762827
doi: 10.2147/OTT.S293834
pii: 293834
pmc: PMC7982712
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1953-1959Informations de copyright
© 2021 Busquets et al.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest related to employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding.
Références
Shock. 2001 Mar;15(3):200-7
pubmed: 11236903
Cancer Res. 2004 Sep 15;64(18):6725-31
pubmed: 15374990
Exp Ther Med. 2011 Jul;2(4):731-735
pubmed: 22977567
Br J Cancer. 2000 Aug;83(4):526-31
pubmed: 10945502
Clin Nutr. 2010 Apr;29(2):154-9
pubmed: 20060626
Nutr Metab (Lond). 2012 Aug 21;9(1):76
pubmed: 22909172
J Cachexia Sarcopenia Muscle. 2014 Dec;5(4):315-20
pubmed: 25167857
Neuromuscul Disord. 2007 Jan;17(1):47-55
pubmed: 17134898
Int J Biochem Cell Biol. 2005 Oct;37(10):2134-46
pubmed: 15893952
Am J Med. 1980 Oct;69(4):491-7
pubmed: 7424938
Arch Biochem Biophys. 1993 Oct;306(1):52-8
pubmed: 8215420
Front Physiol. 2017 Apr 19;8:213
pubmed: 28469577
Clin Nutr. 2012 Dec;31(6):889-95
pubmed: 22608917
Appl Physiol Nutr Metab. 2009 Jun;34(3):389-95
pubmed: 19448704
BMC Cancer. 2011 Nov 23;11:493
pubmed: 22111896
Neurocrit Care. 2009;10(1):103-15
pubmed: 18696266
Support Care Cancer. 2014 May;22(5):1269-75
pubmed: 24389826
Int J Cancer. 1995 Mar 29;61(1):138-41
pubmed: 7705927
Lancet Oncol. 2011 May;12(5):489-95
pubmed: 21296615
Oncol Rep. 2011 Jan;25(1):189-93
pubmed: 21109976
Biochim Biophys Acta. 2013 Mar;1830(3):2770-8
pubmed: 23200745
Clin Nutr. 2008 Dec;27(6):793-9
pubmed: 18718696
Nat Med. 2015 Nov;21(11):1262-1271
pubmed: 26457758
Gynecol Oncol. 2012 Mar;124(3):417-25
pubmed: 22198049
Clin Nutr. 2010 Dec;29(6):733-7
pubmed: 20621398
Br J Cancer. 2004 Mar 8;90(5):996-1002
pubmed: 14997196
Exerc Sport Sci Rev. 2009 Jan;37(1):29-35
pubmed: 19098522
Annu Rev Biochem. 2007;76:367-85
pubmed: 17506640
Biochem Biophys Res Commun. 1994 Jun 15;201(2):682-6
pubmed: 8003002
Am J Clin Nutr. 2006 Sep;84(3):475-82
pubmed: 16960159
CA Cancer J Clin. 2007 Jul-Aug;57(4):225-41
pubmed: 17626119