TY - JOUR
T1 - Effect of aspirin on mitochondrial dysfunction and stress in the pancreas and heart of goto-kakizaki diabetic rats
AU - John, Annie
AU - Amiri, Layla
AU - Shafarin, Jasmin
AU - Howarth, Frank Christopher
AU - Raza, Haider
N1 - Funding Information:
Funding: The authors would like to acknowledge the financial research supports from Sheikh Hamdan Bin Rashid Al Maktoum Award (HR) for Medical Sciences (MRG-01/2011–2012) and research grants (HR), from Research Committee College of Medicine and Health Sciences (NP-14/01) and (NP-20/13) UAE University, U.A.E. The funders had no role in the study design; collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the article for publication.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/9
Y1 - 2021/9
N2 - Our previous study in Goto-Kakizaki (GK) type 2 diabetic rats provided significant evidence that aspirin treatment improves pancreatic β-cell function by reducing inflammatory responses and improving glucose tolerance. In the present study, we aimed to elucidate the mechanism of action of aspirin on the pathophysiology and progression of type 2 diabetic complications in the heart and pancreas of insulin-resistant GK rats. Aspirin treatment demonstrated a reduction in mitochondrial reactive oxygen species (ROS) production and lipid peroxidation, accompanied by improved redox homeostasis. Furthermore, the recovery of metabolic and mitochondrial functions, as well as cytochrome P450 enzyme activities, which were altered in the pancreas and heart of GK rats, were observed. Aspirin treatment brought the activity of CYP 2E1 to the control level in both tissues, whereas the CYP 3A4 level decreased only in the pancreas. This suggests the tissue-specific differential metabolism of substrates in these rats. The recovery of redox homeostasis could be the key target in the improvement of oxidative-stress-dependent alterations in mitochondrial functions which, in turn, facilitated improved energy metabolism in these tissues in the aspirin-treated GK rats. These results may have implications in determining the therapeutic use of aspirin, either alone or in combination with other clinically approved therapies, in insulin-resistant type 2 diabetes.
AB - Our previous study in Goto-Kakizaki (GK) type 2 diabetic rats provided significant evidence that aspirin treatment improves pancreatic β-cell function by reducing inflammatory responses and improving glucose tolerance. In the present study, we aimed to elucidate the mechanism of action of aspirin on the pathophysiology and progression of type 2 diabetic complications in the heart and pancreas of insulin-resistant GK rats. Aspirin treatment demonstrated a reduction in mitochondrial reactive oxygen species (ROS) production and lipid peroxidation, accompanied by improved redox homeostasis. Furthermore, the recovery of metabolic and mitochondrial functions, as well as cytochrome P450 enzyme activities, which were altered in the pancreas and heart of GK rats, were observed. Aspirin treatment brought the activity of CYP 2E1 to the control level in both tissues, whereas the CYP 3A4 level decreased only in the pancreas. This suggests the tissue-specific differential metabolism of substrates in these rats. The recovery of redox homeostasis could be the key target in the improvement of oxidative-stress-dependent alterations in mitochondrial functions which, in turn, facilitated improved energy metabolism in these tissues in the aspirin-treated GK rats. These results may have implications in determining the therapeutic use of aspirin, either alone or in combination with other clinically approved therapies, in insulin-resistant type 2 diabetes.
KW - Aspirin
KW - CYP 450s
KW - GK rat pancreas and heart
KW - Mitochondrial functions
KW - Redox homeostasis
KW - Type 2 diabetes
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U2 - 10.3390/life11090902
DO - 10.3390/life11090902
M3 - Article
AN - SCOPUS:85114456815
SN - 0024-3019
VL - 11
JO - Life
JF - Life
IS - 9
M1 - 902
ER -