Changes in Body Composition of Old Rats at Different Time Points After Dexamethasone Administration

Author(s): Maire Aru, Karin Alev*, Ando Pehme, Priit Purge, Lauri Õnnik, Anu Ellam, Priit Kaasik, Teet Seene.

Journal Name: Current Aging Science

Volume 11 , Issue 4 , 2018

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Abstract:

Background: Aging leads to changes in skeletal muscle quantity and quality and is accompanied with increase in body mass and fat mass, whereas fat-free mass either decreases or remains unchanged. The body composition of rodents has been an important factor for clinical trials in the laboratory. Glucocorticoids such as dexamethasone are widely used in clinical medicine, but may induce myopathy, characterized by muscle weakness, atrophy, and fatigue. In animals treated with glucocorticoids, a dose-dependent reduction of body weight has been observed. This weight loss is usually followed by muscle atrophy and a reduction of several muscle proteins, contributing to impaired muscle function. This study was designed to describe changes in body composition and BMC of 22-month-old rats during 10- and 20-day recovery period after 10-day dexamethasone administration.

Method: Data on body mass, lean body mass, fat mass and bone mineral content of the rats were obtained with dual energy X-ray absorptiometry scan.

Result: Significant reduction in body mass, lean body mass, fat mass and fast-twitch muscle mass was observed after dexamethasone treatment. Body mass, fat mass and fast-twitch muscle mass stayed decreased during 20 days after terminating the hormone administration; lean body mass reached the preadministration level after 20-day recovery period. There were no significant changes in bone mineral density during the recovery period. Dexamethasone treatment gradually reduced hindlimb grip strength that also stayed decreased during the 20-day recovery period.

Conclusion: This study demonstrated that a 10-day period of overexprosure to glycocorticoids induced longlasting changes in old rats’ body composition and these values did not attain the baseline level even after 20-day recovery period.

Keywords: Old rats, dexamethasone administration, body composition, skeletal muscle, recovery, glucocorticoids.

[1]
Feely RS, Larkin LM, Halter JB, Dengel DR. Chemical versus dual energy x-ray absorptiometry for detecting age-associated body compositional changes in male rats. Exp Gerontol 2000; 35: 417-27.
[2]
Seene T, Kaasik P, Riso EM. Review on aging, unloading and reloading: changes in skeletal muscle quantity and quality. Arch Gerontol Geriatr 2012; 54: 374-80.
[3]
Cederna PS, Asato H, Gu X, et al. Motor unit properties of nerve-intact extensor digitorum longus muscle grafts in young and old rats. J Gerontol A Biol Sci Med Sci 2001; 6: B254-8.
[4]
Sugiura M, Kanda K. Progress of age-related changes in properties of motor units in the gastrocnemius muscle of rats. J Neurophysiol 2004; 92: 1357-65.
[5]
Bruce KD, Byrne CD. The metabolic syndrome: common origins of a multifactorial disorder. Postgrad Med J 2009; 85: 614-21.
[6]
Seidell JC, Hautvast JG, Deurenberg P. Overweight: Fat distribution and health risks. Epidemiological observations A review. Infusionstherapie 1989; 16: 276-81.
[7]
Oliveira A, Rodriguez-Artalejo F, Severo M, Lopes C. Indices of central and peripheral body fat: association with non-fatal acute myocardial infarction. Int J Obes (Lond) 2010; 34: 733-41.
[8]
Batchelor TT, Taylor LP, Thaler HT, Posner JB, DeAngelis LM. Steroid myopathy in cancer patients. Neurology 1997; 48: 1234-8.
[9]
Ruff RL, Martyn D, Gordon AM. Glucocorticoid-induced atrophy is not due to impaired excitability of rat muscle. Am J Physiol 1982; 243: E512-21.
[10]
Seene T. Turnover of skeletal muscle contractile proteins in glucocorticoid myopathy. J Steroid Biochem Mol Biol 1994; 50: 1-4.
[11]
Seene T, Kaasik P, Pehme A, Alev K, Riso E-M. The effect of glucocorticoids on the myosin heavy chain isoforms’ turnover in skeletal muscle. J Steroid Biochem Mol Biol 2003; 86: 201-6.
[12]
Chiu CS, Weber H, Adamski S, et al. Non-invasive muscle contraction assay to study rodent models of sarcopenia. BMC Musculoskelet Disord 2011; 12: 246.
[13]
Graves L, Lukert BP. Glucocorticoid-induced osteoporosis. Clin Rev Bone Miner Metab 2004; 2: 79-90.
[14]
Canalis E, Mazziotti G, Giustina A, Bilezikian JP. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int 2007; 18: 1319-28.
[15]
Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 1998; 102: 274-82.
[16]
Hofbauer LC, Gori F, Riggs BL, et al. Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: Potential paracrine mechanisms of glucocorticoid-induced osteoporosis. Endocrinology 1999; 140: 4382-9.
[17]
Böcker W, El Khassawna T, Bauer N, et al. Short-term glucocorticoid treatment causes spinal osteoporosis in ovariectomized rats. Eur Spine J 2014; 23: 2437-48.
[18]
Attaix D, Mosoni L, Dardevet D, Combaret L, Mirand PP, Grizard J. Altered responses in skeletal muscle protein turnover during aging in anabolic and catabolic periods. Int J Biochem Cell Biol 2005; 37: 1962-73.
[19]
Dardevet D, Sornet C, Savary E, Debras E. Patureau-Mirand, Grizard J. Glucocorticoid effects on insulin- and IGF-1-regulated muscle protein metabolism during aging. J Endocrinol 1998; 156: 83-9.
[20]
Goldspink G, Harridge SD. Growth factors and muscle ageing. Exp Gerontol 2004; 39: 1433-8.
[21]
Seene T, Viru A. The catabolic effect of glucocorticoids on different types of skeletal muscle fibres and its dependence upon muscle activity and interaction with anabolic steroids. J Steroid Biochem 1982; 16: 349-52.
[22]
Seene T, Umnova M, Alev K, Pehme A. Effect of glucocorticoids on contractile apparatus of rat skeletal muscle. J Steroid Biochem 1988; 29: 313-7.
[23]
Albanese CV, Diessel E, Genant HK. Clinical applications of body composition measurements using DXA. J Clin Densitom 2003; 6: 75-85.
[24]
Stevenson KT, van Tets IG. Dual-energy X-ray absorptiometry (DXA) can accurately and non-destructively measure the body composition of small, free-living rodents. Physiol Biochem Zool 2008; 81: 373-82.
[25]
Faron KC. Cancer cachexia and fat. Muscle physiology. N Engl J Med 2011; 365: 565-7.
[26]
Kaasik P, Umnova M, Pehme A, et al. Ageing and dexamethasone associated sarcopenia: Peculiarities of regeneration. J Steroid Biochem Mol Biol 2007; 105: 85-90.
[27]
Seene T, Kaasik P. Role of myofibrillar protein catabolism in development of glucocorticoid myopathy: Aging and functional activity aspect. Metabolites 2016; 6: 15.
[28]
Ahtikoski AM, Riso EM, Koskinen SO, Risteli J, Takala TE. Regulation of type IV collagen gene expression and degradation in fast and muscle during dexamethasone treatment and exercise. Pflugers Arch – Eur j Physiol 2003; 448: 123-30.
[29]
Ma K, Mallidis C, Bhasin S, et al. Glucocorticoid-induced skeletal muscle atrophy is associated with upregulation of myostatin gene expression. Am J Physiol Endocrinol Metab 2003; 285: E363-71.
[30]
Auclair D, Garrel DR, Chaouki Zerouala A, Ferland LH. Activation of the ubiquitin pathway in rat skeletal muscle by catabolic doses of glucocorticoids. Am J Physiol 1997; 272: 1007-16.
[31]
Singleton JR, Baker BL, Thorburn A. Dexamethasone inhibits insulin-like growth factor signalling and potentiates myoblast apoptosis. Endocrinology 2000; 141: 2945-50.
[32]
Carballo-Jane E, Pandit S, Santoro JS, et al. Skeletal muscle: a dual system to measure glucocorticoid-dependent transactivation and transrepression of gene regulation. J Steroid Biochem Mol Biol 2004; 88: 191-201.
[33]
Moore DR, Tang JE, Burd NA, Rerecich T, Tarnopolsky MA, Phillips SM. Differential stimulation of myofibrillar and sarcoplasmic protein synthesis with protein ingestion at rest and after resistance exercise. J Physiol 2009; 587: 897-904.
[34]
Moore DR, Atherton PJ, Rennie MJ, Tarnopolsky MA, Phillips SM. Resistance exercise enhances mTOR and MAPK signalling in human muscle over that seen at rest after bolus protein ingestion. Acta Physiol 2011; 201: 365-72.


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Article Details

VOLUME: 11
ISSUE: 4
Year: 2018
Page: [255 - 260]
Pages: 6
DOI: 10.2174/1874609812666190114144238

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