Abstract
BackgroundChronic alcohol ingestion may cause severe biochemical and pathophysiological derangements to skeletal muscle. Unfortunately, these alcohol-induced events may also prime skeletal muscle for worsened, delayed, or possibly incomplete repair following acute injury. As alcoholics may be at increased risk for skeletal muscle injury, our goals were to identify the effects of chronic alcohol ingestion on components of skeletal muscle regeneration. To accomplish this, age- and gender-matched C57Bl/6 mice were provided normal drinking water or water that contained 20% alcohol (v/v) for 18–20 wk. Subgroups of mice were injected with a 1.2% barium chloride (BaCl2) solution into the tibialis anterior (TA) muscle to initiate degeneration and regeneration processes. Body weights and voluntary wheel running distances were recorded during the course of recovery. Muscles were harvested at 2, 7 or 14 days post-injection and assessed for markers of inflammation and oxidant stress, fiber cross-sectional areas, levels of growth and fibrotic factors, and fibrosis.ResultsBody weights of injured, alcohol-fed mice were reduced during the first week of recovery. These mice also ran significantly shorter distances over the two weeks following injury compared to uninjured, alcoholics. Injured TA muscles from alcohol-fed mice had increased TNFα and IL6 gene levels compared to controls 2 days after injury. Total protein oxidant stress and alterations to glutathione homeostasis were also evident at 7 and 14 days after injury. Ciliary neurotrophic factor (CNTF) induction was delayed in injured muscles from alcohol-fed mice which may explain, in part, why fiber cross-sectional area failed to normalize 14 days following injury. Gene levels of TGFβ1 were induced early following injury before normalizing in muscle from alcohol-fed mice compared to controls. However, TGFβ1 protein content was consistently elevated in injured muscle regardless of diet. Fibrosis was increased in injured, muscle from alcohol-fed mice at 7 and 14 days of recovery compared to injured controls.ConclusionsChronic alcohol ingestion appears to delay the normal regenerative response following significant skeletal muscle injury. This is evidenced by reduced cross-sectional areas of regenerated fibers, increased fibrosis, and altered temporal expression of well-described growth and fibrotic factors.
Highlights
Chronic alcohol ingestion may cause severe biochemical and pathophysiological derangements to skeletal muscle
Body weight and voluntary wheel running activity To indirectly assess the severity of muscle injury, we recorded changes to body weight and quantified daily and total, 14-day voluntary wheel running activity in control and alcohol-fed mice
We hypothesized that the influence of chronic alcohol ingestion and severity of skeletal muscle injury may affect voluntary wheel running activity
Summary
Chronic alcohol ingestion may cause severe biochemical and pathophysiological derangements to skeletal muscle. We and others have shown that underlying chronic alcohol abuse may produce a wide range of skeletal muscle defects including type II muscle atrophy, oxidant stress, and anabolic resistance [7,8,9,10,11]; the ability of alcoholic skeletal muscle to regenerate following injury has not been investigated. This issue is clinically relevant as alcoholics may be at increased risk for muscle injuries due in part to peripheral neuropathies and sensory impairments, increased risky behaviors that may include motor vehicle accidents or inter- and intrapersonal violence, or to muscle atrophy with concomitant reductions to strength and reduced ability to safely stabilize the body during a fall [12,13]. These cells have reduced capacity to minimize proteolysis following direct IGF-1 or insulin stimulation [21]
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