Antioxidant (Oxiprovin TM) supplementation and muscle recovery from contusion injury - an in vivo study

[摘要] ENGLISH ABSTRACT: Human studies on the response of muscle to contusion injury are limited,probably due to the large variability in injury severity and the non-specificity ofclinical symptoms reported. To circumvent this problem, several experimentalanimal models have been designed to study muscle damage and regenerationafter contusion injuries. However, the majority of techniques currently used toinduce contusion injury are very invasive and therefore not optimal. Furthermore,published studies regarding clinical treatment of such injuries are limited. Themain aims of this study were therefore: a) to establish and characterise an in vivomodel of non-invasive contusion injury, and b) to assess the effect of pre-injurychronic administration of the antioxidant supplement Oxiprovin™ - a naturalgrape seed extract (GSE) - on skeletal muscle recovery after experimentallyinducedinjury.Two groups of male Wistar rats were subjected to 14 days of oral administrationof isovolaemic placebo (sterile isotonic saline) or GSE (20 mg/kg/day) prior toinduced contusion. Contusion injury was induced with the mass-drop technique,and recovery parameters assessed for up to 14 days post-injury. Placebotreatedrats on average exhibited a 56 % higher creatine kinase (CK) activitywhen compared to the GSE-treated rats when area under the curve (AUC) wascalculated for 14 days post-injury (p < 0.001). In the placebo group, plasmaoxygen radical absorbance capacity (ORAC) was unchanged over time, butmuscle ORAC was significantly increased by day 7 post-injury (p < 0.001). In theGSE group, a significant decrease in both plasma (p < 0.01) and muscle ORAC(p < 0.001) was evident 4 hr after injury, followed by a significant increase by day3 (p < 0.05 and p < 0.001 respectively). CD34+ satellite cell (SC) numbers (quiescent and activated) peaked earlier in GSE-treated rats when compared toplacebo-treated rats (4 hours vs. day 7 post-injury). Total satellite cell number(CD56+) also peaked earlier in GSE-treated rats than in placebo-treated rats (4hours vs. 3 days post-injury), while M-cadherin+ SC numbers (quiescent,activated or proliferating) in both treatment groups were significantly increased 4hours post-injury (p < 0.001), but more so in the placebo group. In GSE-treatedrats when compared to placebo-treated rats, newly generated muscle fibres(displaying central nuclei and MHCf+) both appeared (day 3 vs. day 7 post-injury)and peaked in number (day 3 vs. day 7 post-injury; increase from baseline p <0.001 for both) earlier.The results of this study demonstrate that we have successfully established an invivo model for non-invasive contusion injury in rats. Furthermore, we have shownthat Oxiprovin™: a) increased the ability to scavenge reactive species generatedafter injury and b) resulted in the activation of satellite cells and formation ofnewly generated muscle fibres at an earlier time point, thus accelerating therecovery of skeletal muscle after a standardised contusion injury.

[发布机构] Stellenbosch University