Low dietary zinc promotes cell stress following blast injury (122.5)

Abstract

Increased metallothionein (MT) and extracellular matrix metalloprotease (MMP) activity has been documented in skeletal muscle following ischemia/reperfusion injury (I/R). MTs bind zinc (Zn) and MMPs, possibly affecting activation of the Zn‐dependent mTOR pathway and MMP‐dependent tissue remodeling post‐injury. Because dietary Zn can reduce I/R, we evaluated the effects of 5‐weeks of low‐ and adequate Zn diets on MMP and TIMP expression in muscle following exposure to blast. Thirty‐two anesthetized Wistar rats were exposed to explosive blast (18g Semtex; 120kPa incident pressure); 32 rats served as Controls. Soleus muscle was harvested at 48h and 14d post‐blast. qRT‐PCR was used to quantify mRNA. All blast‐exposed rats exhibited transient bradycardia and bradypnea post‐injury. Loss‐of‐consciousness averaged 200 sec. At 48h post‐injury, there was a blast‐induced (P<0.05), and Zn‐responsive (P<0.05) upregulation of MT‐MMP (4.3‐fold), MMP‐2 (3.0‐fold), TIMP‐1 (5.6‐fold) and TIMP‐2 (3.4‐fold). MMP‐3 and MMP‐9 were inhibited by the blast, and were not responsive to Zn‐supplementation. No differences were observed 14d post‐blast. Our results suggest that exposure to blast activates MMPs acutely in skeletal muscle, and this response is attenuated by 14d. Low Zn diets interfere with the MMP/TIMP response in muscle, suggesting that Zn‐supplementation ameliorates blast‐induced cell stress.Grant Funding Source: Supported by US Army MRMC, US Air Force MSA