Redox Status and Muscle Pathology in Rheumatoid Arthritis: Insights from Various Rat Hindlimb Muscles.

A B Oyenihi,K H Myburgh,C Smith,Y S L Powrie,T Ollewagen

doi:10.1155/2019/2484678

A B Oyenihi, K H Myburgh + Show 3 more

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https://doi.org/10.1155/2019/2484678

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Abstract

Due to atrophy, muscle weakness is a common occurrence in rheumatoid arthritis (RA). The majority of human studies are conducted on the vastus lateralis muscle—a muscle with mixed fiber type—but little comparative data between multiple muscles in either rodent or human models are available. The current study therefore assessed both muscle ultrastructure and selected redox indicators across various muscles in a model of collagen-induced rheumatoid arthritis in female Sprague-Dawley rats. Only three muscles, the gastrocnemius, extensor digitorum longus (EDL), and soleus, had lower muscle mass (38%, 27%, and 25% loss of muscle mass, respectively; all at least P < 0.01), while the vastus lateralis muscle mass was increased by 35% (P < 0.01) in RA animals when compared to non-RA controls. However, all four muscles exhibited signs of deterioration indicative of rheumatoid cachexia. Cross-sectional area was similarly reduced in gastrocnemius, EDL, and soleus (60%, 58%, and 64%, respectively; all P < 0.001), but vastus lateralis (22% smaller, P < 0.05) was less affected, while collagen deposition was significantly increased in muscles. This pathology was associated with significant increases in tissue levels of reactive oxygen species (ROS) in all muscles except the vastus lateralis, while only the gastrocnemius had significantly increased levels of lipid peroxidation (TBARS) and antioxidant activity (FRAP). Current data illustrates the differential responses of different skeletal muscles of the hindlimb to a chronic inflammatory challenge both in terms of redox changes and resistance to cachexia.

Highlights

There can be no doubt that individuals suffering from rheumatoid arthritis (RA) have significantly decreased quality of life
Increased muscle inflammatory cytokine levels, altered expression of genes involved in muscle repair and glycolytic metabolism, as well as increased levels of fibrosis-associated amino acids, correlated with disease progression, physical inactivity, and pain in a large cohort of RA patients [6]
These data, generated from the vastus lateralis muscle, and the finding related to altered glycolytic metabolism, raised the question of whether different muscles or muscles with different fiber type distributions may be differentially sensitive to RAassociated pathology

Summary

Introduction

There can be no doubt that individuals suffering from rheumatoid arthritis (RA) have significantly decreased quality of life. While neuromuscular fatigue (assessed by electromyography) was reported to weakly correlate with subjective perception of fatigue and physical activity level, it did not correlate to either clinical profile or treatment features [5] This suggests that while advancement of emotional well-being should form part of treatment strategy, neuromuscular pathology is probably not a major role player in RA. Increased muscle inflammatory cytokine levels, altered expression of genes involved in muscle repair and glycolytic metabolism, as well as increased levels of fibrosis-associated amino acids, correlated with disease progression, physical inactivity, and pain in a large cohort of RA patients [6] These data, generated from the vastus lateralis muscle, and the finding related to altered glycolytic metabolism, raised the question of whether different muscles or muscles with different fiber type distributions may be differentially sensitive to RAassociated pathology

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