Indomethacin and ibuprofen preserve gastrocnemius muscle mass in mice bearing the colon-26 adenocarcinoma

2004 ◽  
Vol 27 (3) ◽  
pp. 174-184 ◽  
Author(s):  
Donna O. McCarthy ◽  
Pamela Whitney ◽  
Andrew Hitt ◽  
Sadeeka Al-Majid
2004 ◽  
Vol 28 (1) ◽  
pp. 48-55 ◽  
Author(s):  
Erin Graves ◽  
Andrew Hitt ◽  
Michael W. Pariza ◽  
Mark E. Cook ◽  
Donna O. McCarthy

2021 ◽  
Author(s):  
Luca J Delfinis ◽  
Catherine A Bellissimo ◽  
Shivam Gandhi ◽  
Sara N DiBenedetto ◽  
Megan E Rosa-Caldwell ◽  
...  

Muscle weakness and wasting are defining features of cancer-induced cachexia. Mitochondrial stress occurs before atrophy in certain muscles, but distinct responses between muscles and across time remains unclear. We aimed to determine the time-dependent and muscle-specific responses to Colon-26 (C26) cancer-induced cachexia in mice. At 2 weeks post-inoculation, the presence of small tumours did not alter body or muscle mass but decreased force production in the quadriceps and diaphragm. Pyruvate-supported mitochondrial respiration was lower in quadriceps while mitochondrial H2O2 emission was elevated in diaphragm. At 4 weeks, large tumours corresponded to lower body mass, muscle mass, and cross-sectional area of fibers in quadriceps and diaphragm. Force production in quadriceps was unchanged but remained lower in diaphragm vs control. Mitochondrial respiration was increased while H2O2 emission was unchanged in both muscles vs control. Mitochondrial creatine sensitivity was compromised in quadriceps. These findings indicate muscle weakness precedes atrophy in quadriceps and diaphragm but is linked to heterogeneous mitochondrial alterations. Eventual muscle-specific restorations in force and bioenergetics highlight how the effects of cancer on one muscle do not predict the response in another muscle. Exploring heterogeneous responses of muscles to cancer may reveal new mechanisms underlying distinct sensitivities, or resistance, to cancer cachexia.


2007 ◽  
Vol 102 (2) ◽  
pp. 564-572 ◽  
Author(s):  
Kirsten Legerlotz ◽  
Peter Schjerling ◽  
Henning Langberg ◽  
Gert-Peter Brüggemann ◽  
Anja Niehoff

Compared with muscle or bone, there is a lack of information about the relationship between tendon adaptation and the applied loading characteristic. The purpose of the present study was to analyze the effect of different exercise modes characterized by very distinct loading patterns on the mechanical, morphological, and biochemical properties of the Achilles tendon. Sixty-four female Sprague-Dawley rats were divided into five groups: nonactive age-matched control (AMC; n = 20), voluntary wheel running (RT; n = 20), vibration strength-trained (LVST; n = 12), high-vibration strength-trained (HVST; n = 6), and high strength-trained (HST; n = 6) group. After a 12-wk-long experimental period, the Achilles tendon was tested mechanically and the cross-sectional area, the soleus and gastrocnemius muscle mass, and mRNA concentration of collagen I, collagen III, tissue inhibitor of metalloproteinase-1 (TIMP-1), transforming growth factor-β, connective tissue growth factor, and matrix metalloproteinase-2 was determined. Neither in the LVST nor in the HVST group could any adaptation of the Achilles tendon be detected, although the training had an effect on the gastrocnemius muscle mass in the LVST group ( P < 0.05). In the HST group, the highest creep was found, but the effect was more pronounced compared with the LVST group ( P < 0.05) than with the AMC group. That indicates that this was rather induced by the low muscle mass rather than by training. However, the RT group had a higher TIMP-1 mRNA concentration in the Achilles tendon in contrast to AMC group ( P < 0.05), which suggests that this exercise mode may have an influence on tendon adaptation.


2008 ◽  
Vol 40 (Supplement) ◽  
pp. S77
Author(s):  
Tyrone A. Washington ◽  
J. Mark Davis ◽  
Larry L. Lowe ◽  
L. Britt Wilson ◽  
J. Larry Durstine ◽  
...  

2008 ◽  
Vol 294 (2) ◽  
pp. R393-R401 ◽  
Author(s):  
Kristen A. Baltgalvis ◽  
Franklin G. Berger ◽  
Maria Marjorette O. Pena ◽  
J. Mark Davis ◽  
Stephanie J. Muga ◽  
...  

The ApcMin/+mouse has a mutation in the Apc tumor suppressor gene and develops intestinal polyps, beginning at 4 wk of age. This mouse develops cachexia by 6 mo, characterized by significant loss of muscle and fat tissue. The purpose of the present study was to determine the role of circulating interleukin-6 (IL-6) and the polyp burden for the development of cachexia in ApcMin/+mice. At 26 wk of age, mice exhibiting severe cachectic symptoms had a 61% decrease in gastrocnemius muscle weight, complete loss of epididymal fat, a 10-fold increase in circulating IL-6 levels, and an 89% increase in intestinal polyps compared with mildly cachectic animals. ApcMin/+/IL-6−/−mice did not lose gastrocnemius muscle mass or epididymal fat pad mass while overall polyp number decreased by 32% compared with ApcMin/+mice. Plasmid-based IL-6 overexpression in ApcMin/+/IL-6−/−mice led to a decrease in gastrocnemius muscle mass and epididymal fat pad mass and increased intestinal polyp burden. IL-6 overexpression did not induce cachexia in non-tumor-bearing mice. These data demonstrate that IL-6 is necessary for the onset of adipose and skeletal muscle wasting in the ApcMin/+mouse and that circulating IL-6 can regulate ApcMin/+mouse tumor burden.


2021 ◽  
Author(s):  
Yumin Wang ◽  
Satoshi Ikeda ◽  
Katsunori Ikoma

Abstract Mechanical stimulation has benefits for muscle mass and function. Passive stretching is widely performed in clinical rehabilitation medicine. However, the hypertrophic effects of passive repetitive stretching on senescent skeletal muscles against muscle atrophy remain unknown. We used senescence-accelerated model SAM-P8 mice. The gastrocnemius muscle was passively repetitive stretched by manual ankle dorsiflexion for 15 min, 5 days a week for 2 weeks under deep anesthesia. We examined the effects of passive stretching on muscle mass, myofiber cross-sectional area, muscle fiber type and composition, satellite cell content, mRNA expression of the signaling pathways involved in muscle protein synthesis, muscle-specific ubiquitin ligases, and myogenic regulatory factors. The gastrocnemius muscle weight of the stretched side increased compared with that of the unstretched side. In addition to the increase in muscle mass, muscle fiber cross-sectional area of the stretched side was greater than that of the unstretched side. Passive repetitive stretching significantly increased the mRNA expression level of Akt, p70S6K, 4E-BP1, Myf5, myogenin, MuRF1. Passive repetitive stretching promoted skeletal muscle mass and myofiber cross-sectional area in SAM-P8 mice. These hypertrophic observations are attributable to the stretch-activated signaling pathways involved in protein turnover. These findings are applicable to clinical muscle strengthening and sarcopenia prevention.


1987 ◽  
Vol 27 (1) ◽  
pp. 17-20 ◽  
Author(s):  
V. R. Mysorekar ◽  
A. N. Nandedkar

In the literature, there is no information about sexual dimorphism in human muscles. The present work attempts to establish sexual dimorphism in the human gastrocnemius muscle. In the females, the femora are more oblique at the lower end due to a broader pelvis. To counteract this obliquity, presumably, at the knee joint a stronger muscle mass would be needed on the medial side. To test this assumption the gastrocnemius muscle was studied in 26 male and 25 female cadavers. In each case, the two heads of the muscle were detached from their origins and the length of each head was measured. The study showed that in the female, on the right side, the medial head of the muscle was significantly longer.


2014 ◽  
Vol 307 (11) ◽  
pp. E983-E993 ◽  
Author(s):  
Florian A. Britto ◽  
Gwenaelle Begue ◽  
Bernadette Rossano ◽  
Aurélie Docquier ◽  
Barbara Vernus ◽  
...  

REDD1 (regulated in development and DNA damage response 1) has been proposed to inhibit the mechanistic target of rapamycin complex 1 (mTORC1) during in vitro hypoxia. REDD1 expression is low under basal conditions but is highly increased in response to several catabolic stresses, like hypoxia and glucocorticoids. However, REDD1 function seems to be tissue and stress dependent, and its role in skeletal muscle in vivo has been poorly characterized. Here, we investigated the effect of REDD1 deletion on skeletal muscle mass, protein synthesis, proteolysis, and mTORC1 signaling pathway under basal conditions and after glucocorticoid administration. Whereas skeletal muscle mass and typology were unchanged between wild-type (WT) and REDD1-null mice, oral gavage with dexamethasone (DEX) for 7 days reduced tibialis anterior and gastrocnemius muscle weights as well as tibialis anterior fiber size only in WT. Similarly, REDD1 deletion prevented the inhibition of protein synthesis and mTORC1 activity (assessed by S6, 4E-BP1, and ULK1 phosphorylation) observed in gastrocnemius muscle of WT mice following single DEX administration for 5 h. However, our results suggest that REDD1-mediated inhibition of mTORC1 in skeletal muscle is not related to the modulation of the binding between TSC2 and 14-3-3. In contrast, our data highlight a new mechanism involved in mTORC1 inhibition linking REDD1, Akt, and PRAS40. Altogether, these results demonstrated in vivo that REDD1 is required for glucocorticoid-induced inhibition of protein synthesis via mTORC1 downregulation. Inhibition of REDD1 may thus be a strategy to limit muscle loss in glucocorticoid-mediated atrophy.


1965 ◽  
Vol 43 (6) ◽  
pp. 705-710 ◽  
Author(s):  
G. L. A. Graff ◽  
A. J. Hudson ◽  
K. P. Strickland

In this investigation both ascorbic acid and glycogen were determined in rat gastrocnemius muscle after denervation for times ranging from 12 hours to 60 days. To assess more correctly the changes due to denervation, concentrations per unit weight and content per whole muscle were expressed as a percentage of the corresponding value obtained from the contralateral control. The concentrations of ascorbic acid and glycogen in the normal rat gastrocnemius were, respectively, 2.7 ± 0.1 μg (S.E.M. for 51 animals) and 355 (as a glucose equivalent) ± 15 μg (S.E.M. for 52 animals) per 100 mg wet weight. The concentration of ascorbic acid per unit weight showed significant increase (+ 27%) 36 hours after neurotomy and reached five times the control value 60 days after the denervation. The ascorbic acid content of the whole denervated muscle gradually accumulated to a value of 195% of control at 5 days and then declined to a value of 78% at 15 days and 65% at 60 days. In the later stages of atrophy the losses in ascorbic acid were always less than the losses in muscle mass. The glycogen concentration per unit weight remained essentially unchanged for the first 36–48 hours after neurotomy; it then dropped abruptly to 39% of the original value on the 3rd day and stayed at about this level until the 60th day after denervation. In the first 12 hours there appeared to be a slight rise in the glycogen content of the whole denervated muscle. Subsequently, there was a rapid loss of glycogen from 116% of normal at 24 hours to 35% at 3 days; during the same period of time the loss in muscle mass was only 16%. The loss in glycogen content after 60 days represented 94% of the original amount.The observed initial accumulation of ascorbic acid after denervation may reflect a relative increase in active transport (or in situ synthesis) over breakdown mechanisms. The results reported rule out the possibility that a local deficiency in ascorbic acid per unit weight of muscle is a contributory factor to denervation atrophy and show that there is a continuous local accumulation of ascorbic acid.


2018 ◽  
Vol 37 ◽  
pp. S182-S183
Author(s):  
S. Biesek ◽  
J.M. Filho ◽  
A.P. Miro ◽  
A.C.R.D.M. Ferreira ◽  
A.S. Vojciechowski ◽  
...  

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