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

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2019-11, Vol.392 (11), p.1435-1445
• Main Authors: Kumar, Dhirendra, Jena, Geeta Rani, Ram, Mahendra, Lingaraju, Madhu Cholenahalli, Singh, Vishakha, Prasad, Raju, Kumawat, Sanjay, Kant, Vinay, Gupta, Priyanka, Tandan, Surendra Kumar, Kumar, Dinesh
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Complications; Contraction; Cytokines; Diabetes; Diabetes mellitus; Gene expression; Hemin; Histopathology; Inflammation; Neurosciences; Ointments; Original Article; Oxidants; Oxidative stress; Oxidizing agents; Pharmacology/Toxicology; Protoporphyrin; Rodents; Streptozocin; Tin protoporphyrin; Topical application; Wound healing
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-019-01682-7

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.