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International Journal of Pharmaceutical InvestigationNOW IN
Article

Hyperglycemia‑induced intramitochondrial glycogen granules: A potential mechanism of glucose cytotoxicity in brain of mice

Mohd Alaraj1★, Bahaa Deen Al‑Trad2, Samir Qiblawi1, Audah Al Hazmi3, Fahaad S. H. Alenazi1, Ashfaque Hossain4, Tolgahan Acar5, Mohammad Almermesh6, Mohammed Qumani Ahmed1★ Corresponding author

  1. 1Departments of Pharmacology.
  2. 2Department of Biological Sciences, Yarmouk University, Yarmouk, Jordan.
  3. 3Physiology, College of Medicine, University of Hail.
  4. 4Department of Medical Microbiology, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, UAE.
  5. 5Department of Physical Therapy, College of Applied Medical Science, University of Hail.
  6. 6Department of Pharmacy, College of Pharmacy, University of Hail, Hail, KSA.

CORRESPONDENCE

Mohd Alaraj

Departments of Pharmacology.

ibrahim_naseem@yahoo.com

Volume 8, Issue 1 · pp. 33–37 · PUBLISHED · DOI: 10.4103/jphi.JPHI_95_17

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ABSTRACT

Aim:The main objectives of this work were to prove that subcutaneous injection of high doses of glucose can lead to occurrence of glycogen granules inside ultrastructurally changed mitochondria of mouse cerebral cortex and to check whether blocking of mitochondrial permeability transition pore (MPTP) by cyclosporine A would diminish occurrence of these granules inside some mitochondria. By this, we aimed to explore if hyperglycemia‑induced intramitochondrial glycogen granules (HIMG) may represent a molecular pathway through which hyperglycemia may lead to dysfunction of brain mitochondria. Materials and Methods:Electron microscopic studies and histopathological investigations have been carried out. We then incubated samples of brain cortex of mouse injected with high doses of glucose in alpha‑amylase solvent or disolvent alone before being subjected to microscopic examination. Results:Electron microscopy experiments established that the observed granules are built of glycogen. It has been also demonstrated that blocking of MPTP by cyclosporine A diminished occurrence of glycogen inside some mitochondria in cerebral cortex, thus inhibiting hyperglycemia‑induced apoptotic signaling that results from increased vulnerability of mouse brain mitochondria. Concurrently, cyclosporine A partially suppressed the histopathological changes of brain cortex of these animals. Conclusions:Taken together, this study indicates that cytotoxicity of hyperglycemia might occur through HIMG and we postulate this as a key molecular pathway through which hyperglycemia may lead to dysfunction of brain mitochondria. This is the first report showing HIMG as a cytotoxic molecular mechanism in mouse model.

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    Alaraj, M., Al‑Trad, B. D., Qiblawi, S., Hazmi, A. A., Alenazi, F. S. H., Hossain, A., Acar, T., Almermesh, M., & Ahmed, M. Q. (). Hyperglycemia‑induced intramitochondrial glycogen granules: A potential mechanism of glucose cytotoxicity in brain of mice. International Journal of Pharmaceutical Investigation, 8(1), 33–37. https://doi.org/10.4103/jphi.JPHI_95_17