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Journal of Physiology and Biochemistry

, Volume 69, Issue 4, pp 761–778 | Cite as

Adverse cardiac responses to alpha-lipoic acid in a rat-diabetic model: possible mechanisms?

  • Nouf M. AL-Rasheed
  • Nawal M. Al-Rasheed
  • Hala A. Attia
  • Iman H. Hasan
  • Maha Al-Amin
  • Hanaa Al-Ajmi
  • Raeesa A. Mohamad
Original Paper

Abstract

Alpha-lipoic acid (ALA) is widely used as an antioxidant for the treatment of diabetes and its complications; however, the pro-oxidant potential of ALA has recently been reported. This study was designed to investigate whether ALA supplementation could have pro-oxidant effects on cardiac tissues in normal and diabetic rats. Diabetes was induced by a single dose of streptozotocin (STZ; 55 mg/kg (intraperitoneal). Diabetic and normal rats were treated with ALA (100 mg kg−1 day−1) for 45 days. ALA supplementation resulted in oxidative protein damage as evident by significant reduction in the cardiac levels of protein thiol in ALA-treated normal rats (P < 0.01) together with a significant elevation (P < 0.001) in the plasma levels of advanced oxidation protein products in ALA-treated normal rats and in ALA + STZ-diabetic rats compared with the normal control rats. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has emerged as the major source of superoxide anion and enhanced oxidative damage in heart failure. ALA supplementation increased the myocardial immunoreactivity of p47phox subunit of NADPH oxidase in both normal nondiabetic and diabetic rats reflecting its pro-oxidant effect. Data showed that ALA supplementation failed to prevent cardiac complications in diabetic rats and led to cardiac toxicity in normal rats as indicated by pathological changes (cellular infiltration, fibrosis, and degeneration) and by the elevation of serum cardiac biomarkers compared with normal controls. The pro-oxidant effects of ALA suggest that careful selection of appropriate doses of ALA in reactive oxygen species-related diseases are critical.

Keywords

Alpha-lipoic acid Diabetic complication Protein thiol Advanced oxidation protein product Vascular endothelial growth factor 

Notes

Acknowledgments

This research project was supported by a grant from the “Research Centre of the Centre for Female Scientific and Medical Colleges,” Deanship of Scientific Research, King Saud University. In addition, this work was partially supported by Global Research Network for Medicinal Plants (GRNMP) and King Saud University.

Conflict of interest statement

The authors declare no conflict of interest. The sponsor’s studies mainly supported the work financially and had no involvement in the study design, collection, analysis and interpretation of data, writing of the manuscript, and the decision to submit the manuscript for publication.

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Copyright information

© University of Navarra 2013

Authors and Affiliations

  • Nouf M. AL-Rasheed
    • 1
  • Nawal M. Al-Rasheed
    • 1
  • Hala A. Attia
    • 1
    • 2
  • Iman H. Hasan
    • 1
  • Maha Al-Amin
    • 1
  • Hanaa Al-Ajmi
    • 1
  • Raeesa A. Mohamad
    • 3
  1. 1.Department of Pharmacology and Toxicology, College of PharmacyKing Saud UniversityRiyadhKingdom of Saudi Arabia
  2. 2.Department of Biochemistry, Faculty of PharmacyMansoura UniversityMansouraEgypt
  3. 3.Department of Anatomy, College of MedicineKing Saud UniversityRiyadhKingdom of Saudi Arabia

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