Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats

doi:10.1016/j.intimp.2014.03.009

International Immunopharmacology

Volume 20, Issue 2, June 2014, Pages 322-330

https://doi.org/10.1016/j.intimp.2014.03.009 Get rights and content

Highlights

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Curcumin application enhanced the wound contraction in diabetic rats.
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Curcumin decreased the expressions of TNF-α, IL-1β and MMP-9.
•
Curcumin increased the levels of IL-10, SOD, catalase and glutathione peroxidase.
•
Curcumin-treated wounds showed early regeneration of epithelial layer.
•
Anti-inflammatory and antioxidant potential of curcumin caused faster healing.

Abstract

Prolonged inflammation and increased oxidative stress impairs healing in diabetics and application of curcumin, a well known antioxidant and anti-inflammatory agent, could be an important strategy in improving impaired healing in diabetics. So, the present study was conducted to evaluate the cutaneous wound healing potential of topically applied curcumin in diabetic rats. Open excision skin wound was created in streptozotocin induced diabetic rats and wounded rats were divided into three groups; i) control, ii) gel-treated and iii) curcumin-treated. Pluronic F-127 gel (25%) and curcumin (0.3%) in pluronic gel were topically applied in the gel- and curcumin-treated groups, respectively, once daily for 19 days. Curcumin application increased the wound contraction and decreased the expressions of inflammatory cytokines/enzymes i.e. tumor necrosis factor-alpha, interleukin (IL)-1beta and matrix metalloproteinase-9. Curcumin also increased the levels of anti-inflammatory cytokine i.e. IL-10 and antioxidant enzymes i.e. superoxide dismutase, catalase and glutathione peroxidase. Histopathologically, the curcumin-treated wounds showed better granulation tissue dominated by marked fibroblast proliferation and collagen deposition, and wounds were covered by thick regenerated epithelial layer. These findings reveal that the anti-inflammatory and antioxidant potential of curcumin caused faster and better wound healing in diabetic rats and curcumin could be an additional novel therapeutic agent in the management of impaired wound healing in diabetics.

Introduction

Diabetes is a multisystem disorder and complications of diabetes induce physiological changes in tissues and cells that impair the normal healing process. The pathophysiologic relationship between diabetes and impaired healing is complex. The diabetic wounds get stuck in the inflammatory phase featured by continuing influx of neutrophils that release cytotoxic enzymes, free radicals and inflammatory mediators that cause extensive collateral damage to surrounding tissue. These destructive processes outbalance the healing process in such wounds and overproduction of free radicals that induce oxidative stress results in detrimental cytotoxic effects causing delayed wound healing [1], [2]. The increased oxidative stress is one of the most common complications for the delayed wound healing in diabetics [3]. Therefore, reduction/termination of the persistent inflammation and elimination of free radicals by the introduction of an anti-inflammatory agent and antioxidant into the treatment of wounds could be an important strategy to improve healing of diabetic wounds [2].

Several studies in recent years have demonstrated curcumin as an antioxidant and anti-inflammatory agent [4], [5]. Studies have also reported that curcumin alone or in combination possesses wound healing potential as well as protective effects in radiation induced endothelial injuries and mucosal damage in different animal models [6], [7], [8], [9]. Curcumin has shown its wound healing potential in laser-induced wounds, dexamethasone-impaired healing, corticosteroid-impaired hairless rat skin, radiation-impaired healing of excisional wounds and streptozotocin induced diabetic rats as well as genetically diabetic mice [10], [11], [12], [13], [14], [15].

However, to the best of our knowledge detailed time-dependent studies in diabetic rats are lacking. Hence, in view of the high level of oxidative stress and persistent inflammation associated with delayed healing in diabetic wounds, the present study was conducted to investigate the temporal wound healing potential of topically applied curcumin in diabetic rats.

Section snippets

Animals used and wound creation

Healthy adult male Wistar rats (170–200 g) were procured from Laboratory Animal Resource Section, Indian Veterinary Research Institute, Izatnagar (UP), India. Rats were housed in standard polycarbonate cages with ad lib access to feed and water and were maintained on a 12:12-h light dark cycle in a climatically controlled room. The experimental protocols were approved and sanctioned by the Institutional Animal Ethics Committee. All animals received humane care in accordance with the National

Results

The characteristic signs of diabetes were noticeable from the second day of administration of streptozotocin. The signs were persistent elevated blood glucose levels (Table 2), polyphagia, polydipsia, polyuria and loss of body weight. The increased ocular discharge and paraphimosis with bluish coloration of the glans penis were also perceptible.

Discussion

Curcumin possesses strong antioxidant and anti-inflammatory properties, which makes it a unique molecule for wound healing applications in diabetics [4], [5]. In the present study on diabetic rats, in comparison to the control and gel-treated groups, topical application of curcumin caused acceleration in wound healing with marked collagen synthesis and fully regenerated epithelial layer. It was due to the decreased expression of inflammatory cytokines/enzymes i.e. TNF-α, IL-1β and MMP-9, and

Acknowledgments

The authors are thankful to the Director and Joint Director (Academic) of the Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India, for providing the necessary facilities and support for conducting the present study and the Council of Scientific and Industrial Research (CSIR), New Delhi, India, for Senior Research Fellowship (Award letter no: 09/563(0091)/2012.EMR-I) to the first author. We are also thankful to the Director of the Indian Institutes of Technology (IIT), New

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¹: Present address: Department of Veterinary Pharmacology & Toxicology, Lala Lajpat Rai University of Veterinary & Animal Sciences (LUVAS), Hisar-125001, Haryana, India.

View full text

Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats

Highlights

Abstract

Introduction

Section snippets

Animals used and wound creation

Results

Discussion

Acknowledgments

Int Immunopharmacol

J Control Release

Eur J Pharmacol

Methods

J Invest Dermatol

Am J Pathol

J Nutr Biochem

J Invest Dermatol

J Biol Chem

J Invest Dermatol

J Invest Dermatol

J Invest Dermatol

J Invest Dermatol

Biomaterials

Biomaterials

Oral Surg Oral Med Oral Pathol

Acta Histochem

Classifications for wound bed preparation and stimulation of chronic wounds

Wound Repair Regen

The role of oxidative stress in the pathogenesis and therapy of chronic wounds

Hautarzt

Role of nitric oxide, nitroxidative and oxidative stress in wound healing

Pharmacol Rep

The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgene mouse

J Neurosci

Protective effects of curcumin against gamma radiation-induced ileal mucosal damage

Arch Toxicol

Enhancement of wound healing by curcumin in animals

Wound Repair Regen

Protective effects of curcumin on vascular endothelial injuries induced by radiation

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi

Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice

Wound Repair Regen

Curcumin differentially regulates TGF-beta1, its receptors and nitric oxide synthase during impaired wound healing

Biofactors

Effect of curcumin on radiation-impaired healing of excisional wounds in mice

J Wound Care