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Molecular and Cellular Biochemistry

, Volume 449, Issue 1–2, pp 267–276 | Cite as

Regulation of aging and oxidative stress pathways in aged pancreatic islets using alpha-lipoic acid

  • Navid Nobakht-Haghighi
  • Mahban Rahimifard
  • Maryam Baeeri
  • Mohammad Amin Rezvanfar
  • Shermineh Moini Nodeh
  • Hamed Haghi-Aminjan
  • Emre Hamurtekin
  • Mohammad AbdollahiEmail author
Article

Abstract

Oxidative stress has been involved in the aging process and the pathogenesis of type-2 diabetes, which is a serious health problem worldwide. This study investigates the anti-aging, anti-apoptotic, and antioxidant properties of alpha-lipoic acid (ALA), aiming to improve aged rat pancreatic cells. In this regard, half maximal effective concentration (EC50) of ALA based on the survival of aged pancreatic islet cells was determined as 100 µM. Following this, p38 and p53 genes expression as key factors in aging, oxidative stress biomarkers, insulin secretion, and Pdx1 protein expression were evaluated using real-time PCR, ELISA reader, and fluorescence microscope. It was revealed that ALA reduces and controls the effects of aging on beta cells mainly by suppressing p38 and p53 at the gene level (P < 0.001 and P < 0.01), respectively, reducing reactive oxygen species (P < 0.001) and enhancing levels of thiols (P < 0.05) compared with the aged islets. Furthermore, both qualitative and quantitative investigations of insulin secretion have shown that ALA can improve aged cells’ function and increase insulin secretion specially in the stimulating concentration of glucose. Also, the expression of Pdx1 was considerably increased by ALA in comparison to the aged pancreatic islets (P < 0.001). As far as the authors of the present study are concerned, this is the first study, which evaluated aging associated with p38 and p53 pathways, oxidative stress parameters, and the expression of insulin in beta cells of an aged rat and reaffirmed the fact that ALA has a significant antioxidant role in reducing the aging process.

Keywords

Senescence Diabetes Oxidative stress Islet Cells α-Lipoic acid 

Notes

Acknowledgements

This study was mainly self-supported by the corresponding author and in part by TUMS (32716) and INSF (43114) seat awards directed to the corresponding author.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Navid Nobakht-Haghighi
    • 1
    • 2
  • Mahban Rahimifard
    • 2
  • Maryam Baeeri
    • 2
  • Mohammad Amin Rezvanfar
    • 2
  • Shermineh Moini Nodeh
    • 3
  • Hamed Haghi-Aminjan
    • 3
  • Emre Hamurtekin
    • 1
  • Mohammad Abdollahi
    • 2
    • 3
    • 4
    Email author
  1. 1.Faculty of PharmacyEastern Mediterranean UniversityFamagustaCyprus
  2. 2.The Institute of Pharmaceutical Sciences (TIPS)Tehran University of Medical SciencesTehranIran
  3. 3.Department of Toxicology and Pharmacology, Faculty of PharmacyTehran University of Medical SciencesTehranIran
  4. 4.The Institute of Pharmaceutical Sciences (TIPS) and Faculty of PharmacyTehran University of Medical SciencesTehranIran

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