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Drug Res (Stuttg) 2018; 68(06): 355-360
DOI: 10.1055/s-0043-121143
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

PPAR-α Agonist Improves Hyperglycemia-Induced Oxidative Stress in Pancreatic Cells by Potentiating Antioxidant Defense System

Habib Yaribeygi
1   Health Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
2   Chronic Kidney Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
,
Mohammad Taghi Mohammadi
1   Health Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
2   Chronic Kidney Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
,
Amirhossein Sahebkar
3   Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
4   Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
› Author Affiliations
Further Information

Publication History

received 25 August 2017

accepted 09 October 2017

Publication Date:
12 February 2018 (online)

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Abstract

Background Diabetes-induced oxidative stress has an essential role in pancreatic cells dysfunction. The present study aimed to evaluate whether peroxisome proliferator activated receptor- alpha (PPAR-α) induction by fenofibrate counterbalances oxidative stress in pancreatic cells.

Methods In this in vivo study, male Wistar rats were randomly divided into four groups as normal, normal treated, diabetic and diabetic treated groups (n=6 in each group). Diabetes was induced by a single intravenous injection of streptozotocin (45 mg/kg). Treated animals received fenofibrate for 8 weeks (80 mg/kg/day) orally. At the end of the 8th week, rats were sacrificed and blood samples and pancreas tissues were collected. Then, the content of malondialdehyde (MDA), nitrate (Nox) and glutathione (GLT) and enzymatic activities of catalase (CAT) and superoxide dismutase (SOD) were assessed. D ata were analyzed using two-way ANOVA.

Results Diabetes deteriorated anti-oxidant defense capacity in pancreatic cells by reducing SOD and CAT activities and induced oxidative stress as reflected by increased MDA content and free radicals production (Nox content). Treatment by fenofibrate increased SOD and CAT activities and improved oxidative stress by decreasing pancreatic MDA and Nox levels.

Conclusion Uncontrolled hyperglycemia weakens anti-oxidant defense capacity in pancreatic cells and contributes to oxidative stress. PPAR-α induction by fenofibrate can restore anti-oxidant defense systems and improve diabetes-induced oxidative stress.

Key words

oxidative stress - pancreas - PPAR-α - diabetes
 

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