Cytoprotective effects of N-acetylcysteine on streptozotocin-induced oxidative stress and apoptosis in RIN-5F pancreatic β-cells

Arwa M.T. Al-Nahdi, Annie John, Haider Raza

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Background/Aims: Numerous studies have reported overproduction of reactive oxygen species (ROS) and alterations in mitochondrial energy metabolism in the development of diabetes and its complications. The potential protective effects of N-acetylcysteine (NAC) in diabetes have been reported in many therapeutic studies. NAC has been shown to reduce oxidative stress and enhance redox potential in tissues protecting them against oxidative stress associated complications in diabetes. In the current study, we aimed to investigate the molecular mechanisms of the protective action of NAC on STZ-induced toxicity in insulin secreting Rin-5F pancreatic β-cells. Methods: Rin-5F cells were grown to 80% confluence and then treated with 10mM STZ for 24h in the presence or absence of 10mM NAC. After sub-cellular fractionation, oxidative stress, GSH-dependent metabolism and mitochondrial respiratory functions were studied using spectrophotometric, flow cytometric and Western blotting techniques. Results: Our results showed that STZ-induced oxidative stress and apoptosis caused inhibition in insulin secretion while NAC treatment restored the redox homeostasis, enhanced insulin secretion in control cells and prevented apoptosis in STZ-treated cells. Moreover, NAC attenuated the inhibition of mitochondrial functions induced by STZ through partial recovery of the mitochondrial enzymes and restoration of membrane potential. STZ-induced DNA damage and expression of apoptotic proteins were significantly inhibited in NAC-treated cells. Conclusion: Our results suggest that the cytoprotective action of NAC is mediated via suppression of oxidative stress and apoptosis and restoration of GSH homeostasis and mitochondrial bioenergetics. This study may, thus, help in better understanding the cellular defense mechanisms of pancreatic β-cells against STZ-induced cytotoxicity.

Original languageEnglish
Pages (from-to)201-216
Number of pages16
JournalCellular Physiology and Biochemistry
Volume51
Issue number1
DOIs
Publication statusPublished - Nov 1 2018

Keywords

  • Apoptosis
  • N-acetylcysteine
  • Oxidative stress
  • Pancreatic Rin-5F cells
  • Streptozotocin

ASJC Scopus subject areas

  • Physiology

Fingerprint

Dive into the research topics of 'Cytoprotective effects of N-acetylcysteine on streptozotocin-induced oxidative stress and apoptosis in RIN-5F pancreatic β-cells'. Together they form a unique fingerprint.

Cite this