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Possible vasculoprotective role of linagliptin against sodium arsenite-induced vascular endothelial dysfunction

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Abstract

Vascular endothelial dysfunction (VED) interrupts the integrity and function of endothelial lining through enhanced markers of oxidative stress and decrease endothelial nitric oxide synthase (eNOS) expression. The main aim of the present study has been designed to investigate the possible vasculoprotective role of linagliptin against sodium arsenite-induced VED. Sodium arsenite (1.5 mg/kg, i.p., 2 weeks) abrogated the acetylcholine-induced, endothelium-dependent vasorelaxation by depicting the decrease in serum nitrite/nitrate concentration, reduced glutathione level, and simultaneously enhance the thiobarbituric acid reactive substances (TBARS) level, superoxide level, and tumor necrosis factor-alpha. These elevated markers interrupt the integrity of endothelial lining of thoracic aorta which was assessed histologically. The study elicits dose dependent effect of linagliptin (1.5 mg/kg, i.p. and 3 mg/kg, i.p.) or atorvastatin (30 mg/kg, p.o.) treatment, improved the endothelium-dependent independent relaxation, improve the integrity of endothelium lining which was assessed histologically by enhancing the serum nitrite/nitrate level, reduced glutathione level and simultaneously decreasing the TBARS level, superoxide anion level and tumor necrosis factor-alpha (TNF-α) level. L-NAME (25 mg/kg, i.p.), eNOS inhibitor, abrogated the ameliorative potential of linagliptin. However, the ameliorative potential of linagliptin has been enhanced by l-arginine (200 mg/kg, i.p.) which elicits that ameliorative potential of linagliptin was through eNOS signaling cascade and it may be concluded that linagliptin 3 mg/kg, i.p. has more significantly activated the eNOS and decreased the oxidative markers than linagliptin 1.5 mg/kg, i.p. and prevented sodium arsenite-induced VED.

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Acknowledgments

The authors are thankful to the management and teaching faculty of ISF College of Pharmacy, Moga, India, for providing requisite facilities. Special thanks to Dr. R. K. Goel, Professor, DPSDR, Punjabi University, Patiala, India, for his technical help.

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Authors and Affiliations

  1. University Institute of Pharmaceutical Sciences and Research, Baba Farid University of Health Sciences, Faridkot, Punjab, 151 203, India

    Uma Jyoti, Sunil Kumar Kansal & Sandeep Goyal

  2. Cardiovascular Division, ISF College of Pharmacy, Moga, Punjab, 142 001, India

    Puneet Kumar

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  1. Uma Jyoti
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  2. Sunil Kumar Kansal
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  4. Sandeep Goyal
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Correspondence to Sandeep Goyal.

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Jyoti, U., Kansal, S.K., Kumar, P. et al. Possible vasculoprotective role of linagliptin against sodium arsenite-induced vascular endothelial dysfunction. Naunyn-Schmiedeberg's Arch Pharmacol 389, 167–175 (2016). https://doi.org/10.1007/s00210-015-1184-4

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  • DOI: https://doi.org/10.1007/s00210-015-1184-4

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