Myocardial ischemia and reperfusion injury in rats: lysosomal hydrolases and matrix metalloproteinases mediated cellular damage |
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Authors: | Mitali Tiwari Thiagarajan Hemalatha Kalaivani Ganesan Mohammed Nayeem Bhakthavatsalam Murali Manohar Chidambaram Balachandran Subbiah Vairamuthu Samu Subramaniam Rengarajulu Puvanakrishnan |
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Institution: | (1) Department of Biotechnology, Central Leather Research Institute, Adyar, Chennai, 600020, India;(2) Alved Pharma and Foods Pvt. Ltd, Chennai, India;(3) Centre for Animal Health studies, Tamil Nadu Veterinary and Animal Sciences University, Madhavaram, Chennai, India;(4) Department of Veterinary Pathology, Madras Veterinary College, Chennai, India;(5) Department of Biochemistry, Apollo Hospitals, Chennai, India |
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Abstract: | 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 β-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. |
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Keywords: | Ischemia Reperfusion injury Acid hydrolases Matrix metalloproteinase Collagen |
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