Estudo do potencial efeito antioxidante do extrato fracionado da soja no músculo esquelético distrófico de camundongos mdx

Abstract

Calcium influx is one of the main mechanisms involved in muscle degeneration in Duchenne muscular dystrophy (DMD). Excess calcium in the cytoplasm of dystrophic muscle cells accumulates in the mitochondria, This process intensifies the production of reactive oxygen species (ROS), triggering oxidative stress and inflammation. In mdx mice, genistein demonstrated superior antioxidant effects and benefits when administered as part of soy extract, compared to genistein alone. This study investigates the antioxidant effect of fractionated soy extract containing 2 mg/kg genistein on dystrophic muscle of mdx mice. The following techniques were performed: analysis of the toxicity of fractionated soy extract (AST and ALT); CK analysis; histopathological analysis of liver and kidneys; strength assessment before, during and after treatments; quantification of lipofuscin granules in muscles and analysis of the DHE area of the BB, DIA, TA and EDL muscles; levels of CAT, SOD2, NF-kB and 4-HNE in the BB and DIA muscles; GSH dosage in the BB, DIA, TA and EDL muscles; analysis of the inflammation and macrophage area of the BB, DIA, TA and EDL muscles; quantification of IgG-positive fibers and quantification of fibers with a central nucleus in the BB, DIA, TA and EDL muscles. Isoflavone-rich soybean extract had no toxic effect in mdx mice and attenuated muscle damage (increased muscle strength and reduced IgG-positive (21%-BB; 65.7%- DIA; 50.6%-TA and 37%-EDL) and CK (92.5%) levels), the inflammatory process (reduced NF-κB (58.2%-BB; 46.9%-DIA)), inflammatory area (7.9%-BB; 44.6%-DIA and 8.3%-TA) and macrophages (21.3%-BB and 89.2%-DIA)) and oxidative stress ((reduced the production of ROS (19.1%-BB and 62.4%-DIA), 4-HNE (18.1%-BB), lipofuscin (67.7%-BB; 46.9%-DIA; 60.8%-TA and 33.2%-EDL) and increased catalase and GSH levels (37.2% and 58.5%-BB)); and modulated regeneration (increased centralized nuclei (11.4%-BB; 120.1%-DIA; 11%-TA and 25.7%-EDL)). Soy extract rich in isoflavones proved to be safe and beneficial in the mdx mouse model, promoting improved muscle function and reducing myopathy.