Repercussions of adjuvant-induced arthritis on body composition, soleus muscle, and heart muscle of rats

Abstract

This study investigated the repercussions of adjuvant-induced arthritis (AIA) on body composition and the structural organization of the soleus and cardiac muscles, including their vascularization, at different times of disease manifestation. Male rats were submitted to AIA induction by intradermal administration of 100 μL of Mycobacterium tuberculosis (50 mg/mL), in the right hind paw. Animals submitted to AIA were studied 4 (AIA4), 15 (AIA15), and 40 (AIA40) days after AIA induction as well as a control group of animals not submitted to AIA. Unlike the control animals, AIA animals did not gain body mass throughout the evolution of the disease. AIA reduced food consumption, but only on the 40th day after induction. In the soleus muscle, AIA reduced the wet mass in a time-dependent manner but increased the capillary density by the 15th day and the fiber density by both 15 and 40 days after induction. The diameter of the soleus fiber decreased from the 4th day after AIA induction as well as the capillary/fiber ratio, which was most evident on the 40th day. Moreover, AIA induced slight histopathological changes in the cardiac muscle that were more evident on the 15th day after induction. In conclusion, AIA-induced changes in body composition as well as in the soleus muscle fibers and vasculature have early onset but are more evident by the 15th day after induction. Moreover, the heart may be a target organ of AIA, although less sensitive than skeletal muscles.

Figure 1.. Right (A) and left (B) hind paw diameter determined in control (CTRL) animals or in those submitted to adjuvant-induced arthritis (AIA), 4 days (AIA4), 15 days (AIA15), and 40 days (AIA40) after induction. Data are reported as means±SE. The number of independent samples is reported in parentheses. *P<0.0001 vs CTRL; ^#P<0.05 vs AIA4; ^@P≤0.05 vs AIA15 (one-way ANOVA, followed Tukey's post-test).

Figure 2.. Values of body weight (A), fat mass (B), and lean mass (C) determined in control (CTRL) animals or in those submitted to adjuvant-induced arthritis (AIA) 4 days (AIA4), 15 days (AIA15), and 40 days (AIA40) after induction. Data are reported as means±SE. The number of independent samples is reported in parentheses. ^aP<0.01 vs CTRL assessed on the 4th day after false-immunized; ^bP≤0.05 vs CTRL assessed on the 15th day after false-immunized; ^cP<0.01 vs CTRL assessed on the 40th day after false-immunized. *P<0.01 vs CTRL; ^#P≤0.05 vs AIA4; ^@P<0.01 vs AIA15 (one-way ANOVA, followed Tukey's post-test).

Figure 3.. Photomicrographs of soleus (A-D) and cardiac (E-H) muscles taken from control (CTRL) animals or those submitted to adjuvant-induced arthritis (AIA) 4 days (AIA4), 15 days (AIA15), and 40 days (AIA40) after induction. In the control groups, the soleus and cardiac muscles exhibited normal morphology (A, E). In the AIA groups, at all times after induction, the soleus muscle showed signs of damage (B-B _2, C-C _2, D-D ₂). In the cardiac muscle, AIA promoted inflammatory infiltrate 15 days after induction (G, G-inset) and apparent atrophy in cardiomyocytes 40 days (H) after induction compared with AIA4 (F). BV: blood vessels; star: normal muscle fibers; non-filled arrowhead: leukocyte migration; asterisk: atrophied fibers; arrowhead: nuclear aggregation; arrow: inflammatory infiltrate. Staining: hematoxylin and eosin. Magnification bars: A, B, D-H, 50 μm; C, B ₁-D _1, B ₂-D ₂, 20 μm; G-inset, 50 μm.