Aging-associated oxidative stress modulates the acute inflammatory response in skeletal muscle after contusion injury

Abstract

Inflammation is an integral component of the response of skeletal muscle to a contusion injury that can be modulated by acute oxidative stress. Less is known regarding the effect of aging-associated oxidative stress on the inflammatory response in injured skeletal muscle. The purpose of this project was to assess the level of oxidative stress in skeletal muscles of young, adult, and old rats and determine its effect on the acute inflammatory response to a contusion injury. Inherent oxidative stress in the muscle was determined by measuring the glutathione:glutathione disulfide ratio, and levels of GP91(phox). Elevated oxidative stress was observed in uninjured muscles of adult and old rats and was accompanied by increased levels of lipid peroxidation and neutrophil chemoattractant CINC-1. After injury, the acute inflammatory response (8h, 3 d) was determined from markers of neutrophil (myeloperoxidase) and macrophage (CD68) content and by expression of NFkappaB, CINC-1 and TGF-beta1. Compared to injured muscles of young rats, NFkappaB, myeloperoxidase activity (8h), macrophage content (3 d), and TGF-beta1 (8h and 3 d) were significantly greater in injured muscles of old rats. We conclude that aging-associated oxidative stress in muscles of old rats exacerbated the inflammatory response to contusion injury and leads to increased TGF-beta1-induced collagen content.