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Hemin attenuated oxidative stress and inflammation to improve wound healing in diabetic rats

  • Dhirendra KumarEmail author
  • Geeta Rani Jena
  • Mahendra Ram
  • Madhu Cholenahalli Lingaraju
  • Vishakha Singh
  • Raju Prasad
  • Sanjay Kumawat
  • Vinay Kant
  • Priyanka Gupta
  • Surendra Kumar Tandan
  • Dinesh Kumar
Original Article
  • 8 Downloads

Abstract

Oxidative stress and persistent inflammation play crucial role in the progression of diabetic wound complications. Hemeoxgenase-1 (HO-1) by degrading hemin has been shown to display anti-oxidant and anti-inflammatory effects. Further, hemin is a potent HO-1 inducer. Thus, the current study was aimed to evaluate the effect of topical application of hemin on diabetic wound in rats. Four hundred square millimeter open excision wound were created 2 weeks after induction of diabetes with single intraperitoneal injection of streptozotocin (60 mg/kg), and the diabetic rats were divided into three groups namely diabetic control, hemin, and tin protoporphyrin (SnPPIX). Ointment base, hemin (0.5% in ointment base), and SnPPIX (0.5% in ointment base) were applied topically to wounded area in diabetic control, hemin, and SnPPIX group rats, respectively, twice daily for 19 days. Hemin significantly increased the wound contraction in comparison to control and SnPPIX-treated rats. Time-dependent analysis revealed significant increase in anti-oxidants with concomitant decrease in oxidants in hemin-treated rats as compared to diabetic control rats. Further, mRNA expression decreased for inflammatory cytokine and increased for anti-inflammatory cytokine in hemin group as compared to diabetic control rats. Expression of HO-1 also increased in hemin group as compared to diabetic control rats. However, SnPPIX group results were in disagreement with results of hemin which is clearly reflected in histopathology. Results indicate the ability of hemin to accelerate wound healing in diabetic rats by combating inflammation and oxidative stress probably via HO-1.

Keywords

Diabetes Wound Hemin Tin protoporphyrin Oxidative stress Inflammation 

Notes

Authors’ contribution

DK, MR, VK, and DK conceived and designed the research program. DK, MCL, VS, RP, and SK conducted the experiments. RP, VK, and PG conducted the mRNA studies. DK, GRJ, and SKT analyzed the data. DK and SKT interpreted the results. DK, GRJ, and DK wrote the manuscript. All authors read and approved the manuscript.

Funding information

The Director the Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India, provided the necessary funds and facilities for conducting the present study to the first author.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All the experimental procedures conducted on animals (Wistar rats) were in compliance with at least the Declaration of the National Institutes of Health Guide for Care and Use of Laboratory Animals. The experimental procedures and protocols were duly approved by the Institutional Animal Ethics Committee of Indian Veterinary Research Institute, Izatnagar, India.

This article does not contain any studies with human participants performed by any of the authors.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Dhirendra Kumar
    • 1
    Email author
  • Geeta Rani Jena
    • 2
  • Mahendra Ram
    • 1
  • Madhu Cholenahalli Lingaraju
    • 1
  • Vishakha Singh
    • 1
  • Raju Prasad
    • 1
  • Sanjay Kumawat
    • 1
  • Vinay Kant
    • 1
  • Priyanka Gupta
    • 1
  • Surendra Kumar Tandan
    • 1
  • Dinesh Kumar
    • 1
  1. 1.Division of Pharmacology and ToxicologyIndian Veterinary Research InstituteIzatnagarIndia
  2. 2.Department of Clinical Medicine, College of Veterinary Science and Animal HusbandryOUATBhubaneswarIndia

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