Myocardial ischemia and reperfusion injury in rats: lysosomal hydrolases and matrix metalloproteinases mediated cellular damage

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 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.

Disassembly of All SNARE Complexes by N-Ethylmaleimide-sensitive Factor (NSF) Is Initiated by a Conserved 1:1 Interaction between α-Soluble NSF Attachment Protein (SNAP) and SNARE Complex*

“…VAMP7-syntaxin4-SNAP23 participates in synaptotagmin VII-regulated lysosomal exocytosis in fibroblasts (23). VAMP8-syntaxin4-SNAP23 is involved in cytokine/chemokine trafficking by segregating lysosomal secretory granules in mast cells (24). These four different ternary SNARE complexes allowed us to test if NSF-driven disassembly is influenced by primary sequence variation of the SNARE core domains and by differences in the N-terminal domains ( i.e.…”

Phloroglucinol, a nutraceutical for IR‐induced cardiac damage in diabetic rats

“…Cytokines and reactive oxygen species mobilize acid hydrolases, which damage myofibrillar proteins, leading to increases in infarct size and eventually to apoptosis or necrosis of the heart tissue . Phloroglucinol treatment significantly reduced oxidative stress by elevating antioxidant enzyme levels, which might be a possible cause of the reduction of infarct size in treated diabetic rats.…”

Biochemical Indices of Cardaic Function of Albino Wistar Rats Exposed to Hippocratea Africana Root Bark Extract

“…Serum total CK activity and CK-MB concentration rise in parallel following myocardial injury. A significant elevation in the level of CK-MB has been observed in the heart effluent during myocardial ischemia band reperfusion in isolated rat hearts [32]. Jaffe et al, (2000) also reported that serum CK-MB is considerably more specific for myocardial damage [33].…”