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Skeletal muscle myopenia in mice model of bile duct ligation and carbon tetrachloride ‐ induced liver cirrhosis

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ABSTRACT

Skeletal muscle myopathy is universal in cirrhotic patients, however, little is known about the main mechanisms involved. The study aims to investigate skeletal muscle morphological, histological, and functional modifications in experimental models of cirrhosis and the principal molecular pathways responsible for skeletal muscle myopathy. Cirrhosis was induced by bile duct ligation (BDL) and carbon tetrachloride (CCl4) administration in mice. Control animals (CTR) underwent bile duct exposure or vehicle administration only. At sacrifice, peripheral muscles were dissected and weighed. Contractile properties of extensor digitorum longus (EDL) were studied in vitro. Muscle samples were used for histological and molecular analysis. Quadriceps muscle histology revealed a significant reduction in cross‐sectional area of muscle and muscle fibers in cirrhotic mice with respect to CTR. Kinetic properties of EDL in both BDL and CCl4 were reduced with respect to CTR; BDL mice also showed a reduction in muscle force and a decrease in the resistance to fatigue. Increase in myostatin expression associated with a decrease in AKT‐mTOR expressions was observed in BDL mice, together with an increase in LC3 protein levels. Upregulation of the proinflammatory citochines TNF‐a and IL6 and an increased expression of NF‐kB and MuRF‐1 were observed in CCl4 mice. In conclusion, skeletal muscle myopenia was present in experimental models of BDL and CCl4‐induced cirrhosis. Moreover, reduction in protein synthesis and activation of protein degradation were the main mechanisms responsible for myopenia in BDL mice, while activation of ubiquitin‐pathway through inflammatory cytokines seems to be the main potential mechanism involved in CCl4 mice.

No MeSH data available.


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Physiological properties of extensor digitorum longus muscles from experimental groups. Functional performance and contractile properties of extensor digitorum longus muscles were compared by dF/dt, −dF/dt, tetanic force, specific force, and time to fatigue. All measurements are presented as mean ± SEM (#P < 0.05 vs. CTR‐CCl4; *P < 0.05 vs. CTR‐BDL); n ≥ 3; BDL, bile duct ligation; CCl4, Carbon tetrachloride.
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phy213153-fig-0005: Physiological properties of extensor digitorum longus muscles from experimental groups. Functional performance and contractile properties of extensor digitorum longus muscles were compared by dF/dt, −dF/dt, tetanic force, specific force, and time to fatigue. All measurements are presented as mean ± SEM (#P < 0.05 vs. CTR‐CCl4; *P < 0.05 vs. CTR‐BDL); n ≥ 3; BDL, bile duct ligation; CCl4, Carbon tetrachloride.

Mentions: Among the functional parameters analyzed, we observed a slowing down of the kinetic properties of EDL muscle, as expressed by the dF/dt (Fig. 5A) and the −dF/dt (Fig. 5B). Of note, the BDL treatments induced more severe functional alterations, compared with CCl4 treatments, as revealed by the significant reduction in the tetanic force, the reduction in specific force, and by the significant reduction in the time to fatigue (−38%) (Fig. 5C–E). No direct significant effects of CCl4 treatment seems to appear in the specific force.


Skeletal muscle myopenia in mice model of bile duct ligation and carbon tetrachloride ‐ induced liver cirrhosis
Physiological properties of extensor digitorum longus muscles from experimental groups. Functional performance and contractile properties of extensor digitorum longus muscles were compared by dF/dt, −dF/dt, tetanic force, specific force, and time to fatigue. All measurements are presented as mean ± SEM (#P < 0.05 vs. CTR‐CCl4; *P < 0.05 vs. CTR‐BDL); n ≥ 3; BDL, bile duct ligation; CCl4, Carbon tetrachloride.
© Copyright Policy - creativeCommonsBy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5392502&req=5

phy213153-fig-0005: Physiological properties of extensor digitorum longus muscles from experimental groups. Functional performance and contractile properties of extensor digitorum longus muscles were compared by dF/dt, −dF/dt, tetanic force, specific force, and time to fatigue. All measurements are presented as mean ± SEM (#P < 0.05 vs. CTR‐CCl4; *P < 0.05 vs. CTR‐BDL); n ≥ 3; BDL, bile duct ligation; CCl4, Carbon tetrachloride.
Mentions: Among the functional parameters analyzed, we observed a slowing down of the kinetic properties of EDL muscle, as expressed by the dF/dt (Fig. 5A) and the −dF/dt (Fig. 5B). Of note, the BDL treatments induced more severe functional alterations, compared with CCl4 treatments, as revealed by the significant reduction in the tetanic force, the reduction in specific force, and by the significant reduction in the time to fatigue (−38%) (Fig. 5C–E). No direct significant effects of CCl4 treatment seems to appear in the specific force.

View Article: PubMed Central - PubMed

ABSTRACT

Skeletal muscle myopathy is universal in cirrhotic patients, however, little is known about the main mechanisms involved. The study aims to investigate skeletal muscle morphological, histological, and functional modifications in experimental models of cirrhosis and the principal molecular pathways responsible for skeletal muscle myopathy. Cirrhosis was induced by bile duct ligation (BDL) and carbon tetrachloride (CCl4) administration in mice. Control animals (CTR) underwent bile duct exposure or vehicle administration only. At sacrifice, peripheral muscles were dissected and weighed. Contractile properties of extensor digitorum longus (EDL) were studied in vitro. Muscle samples were used for histological and molecular analysis. Quadriceps muscle histology revealed a significant reduction in cross&#8208;sectional area of muscle and muscle fibers in cirrhotic mice with respect to CTR. Kinetic properties of EDL in both BDL and CCl4 were reduced with respect to CTR; BDL mice also showed a reduction in muscle force and a decrease in the resistance to fatigue. Increase in myostatin expression associated with a decrease in AKT&#8208;mTOR expressions was observed in BDL mice, together with an increase in LC3 protein levels. Upregulation of the proinflammatory citochines TNF&#8208;a and IL6 and an increased expression of NF&#8208;kB and MuRF&#8208;1 were observed in CCl4 mice. In conclusion, skeletal muscle myopenia was present in experimental models of BDL and CCl4&#8208;induced cirrhosis. Moreover, reduction in protein synthesis and activation of protein degradation were the main mechanisms responsible for myopenia in BDL mice, while activation of ubiquitin&#8208;pathway through inflammatory cytokines seems to be the main potential mechanism involved in CCl4 mice.

No MeSH data available.


Related in: MedlinePlus