Myocardial ischemia and reperfusion injury in rats: lysosomal hydrolases and matrix metalloproteinases mediated cellular damage.
The aim of this study was to evaluate the time course events of cellular damage during myocardial ischemia and reperfusion injury in rats and to find out a correlation between the structural alterations with respect to the biochemical changes. Cardiac biomarkers and lysosomal enzymes viz. cathepsin D, acid phosphatase and beta-glucuronidase and matrix metalloproteinases (MMPs) were evaluated at different time points, in response to ischemia-reperfusion induced oxidative stress in an isolated rat heart model perfused in Langendorff mode. Microscopically, changes in myocardial architecture, myofibrillar degradation, and collagen (COL) integrity were studied using hematoxylin-eosin, Masson's trichrome and toluidine blue staining techniques. A three-fold increase in the level of myoglobin was observed after 30 min of ischemia followed by 120 min of reperfusion as compared to 15 min ischemia, 120 min reperfusion. Similarly, a significant increase (P<0.05) in the levels of lipid peroxides and superoxide anion coupled with a decrease in enzymatic and nonenzymatic antioxidant levels were observed. A concomitant increase in the activity of cathepsin D (24.07+/-0.95) and a higher expression of MMPs after 120 min of reperfusion following 30 min ischemia were shown to correlate with the myocardial damage as shown by histopathology, suggesting that free radical induced activation of cathepsin D and MMPs could mediate early damage during myocardial ischemia and reperfusion.
Tiwari
Mitali
M
Department of Biotechnology, Central Leather Research Institute, Adyar, Chennai 600020, India.
Hemalatha
Thiagarajan
T
Ganesan
Kalaivani
K
Nayeem
Mohammed
M
Murali Manohar
Bhakthavatsalam
B
Balachandran
Chidambaram
C
Vairamuthu
Subbiah
S
Subramaniam
Samu
S
Puvanakrishnan
Rengarajulu
R
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004487:Edema / Q000473:pathology; D004562:Electrocardiography; D006867:Hydrolases / Q000378:metabolism / Q000502:physiology*; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism / Q000502:physiology*; D017202:Myocardial Ischemia / Q000201:enzymology / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D015415:Biomarkers; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D003094:Collagen; D006867:Hydrolases; D020782:Matrix Metalloproteinases