ROLE OF THE COAGULATION SYSTEM IN b CELL LOSS INDUCED BY STREPTOZOTOCIN (STZ): FIBRINOLYTIC FUNCTIONAL INSIGHTS
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Keywords
Coagulation system, Fibrinolytic, Type 1 diabetes mellitus, Pancreatic β cells, Alteplase, Streptokinase
Abstract
Background: Diabetes mellitus is a chronic metabolic disorder that dysregulates blood glucose levels. This study aims to assess the role of the coagulation system activation in the initiation of type 1 diabetes millets (T1DM) and the potential effect of certain fibrinolytic agents, specifically streptokinase (STK) and alteplase (ALT) against T1DM and insulin secretion.
Methods: Sixty male Balb/c mice were randomly distributed equally into six groups including normal control, STK, ALT, streptozotocin (STZ), STZ + STK and STZ +ALT. Induction of T1DM was carried out using i.p injection of STZ at a dose of 55 mg/kg body weight for 5 consecutive days in the presence or absence of a single dose of STK (i.v in 8000 IU/kg) or ALT (i.v. in 0.9 mg/kg) on the fifth day of the experiment. Protein expression in the pancreatic tissues for insulin, PAR-2, p-AKT, and PI3K was assessed using immunofluorescence assay and histopathological and nuclear changes were evaluated using hematoxylin and eosin and DAPI stains. Serum insulin level, blood glucose and platelet count were recorded. Results: STZ-induced diabetic mice demonstrated increased expression of PAR-2, p-AKT and PI3K along with notable histopathological and nuclear changes, while insulin expression significantly decreased in pancreatic islets compared to control mice. Conversely, STZ-induced diabetic mice treated with STK or ALT improved the protein expression of insulin, PAR-2, p-AKT and PI3K as well as improved histopathological and nuclear changes caused by STZ-induction.
Conclusion: Activation of the coagulation system plays a vital role in the development β -cell death and hyperglycemia in T1DM. In addition, STK and ALT mitigated the adverse effects resulting from STZ-induction with STK demonstrating superior efficacy compared to ALT in preventing the diabetes onset.
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Abdullah T. Alharbi
Department of Pharmacology and Toxicology, College of Pharmacy, Buraydah 51452, Qassim University, Kingdom of Saudi Arabia
Department of Pharmaceutical Care, Qassim Armed Forces Hospital, Buraydah, 51452, Saudi Arabia
Ahmad H. Alhowail
Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Kingdom of Saudi Arabia.
Salman A. A. Mohammed
Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Kingdom of Saudi Arabia.
Mohamed S. Abdel-Bakky
Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Kingdom of Saudi Arabia.