BioDiscovery : Research Article
Corresponding author: Madalene Heng (email@example.com)
Academic editor: Nikolai Zhelev
Received: 15 Nov 2016 | Accepted: 02 Feb 2017 | Published: 24 Feb 2017
© 2017 Madalene Heng
This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation: Heng M (2017) Phosphorylase Kinase Inhibition Therapy in Burns and Scalds. BioDiscovery 20: e11207. https://doi.org/10.3897/biodiscovery.20.e11207
Severe burns and scalds almost always result in unsightly hypertrophic scarring. Among the important processes involved in scarring are fibroblast formation and transformation of fibroblasts into myofibroblasts. Myofibroblasts contain α-smooth muscle actin which has contractile properties and can lead to wound contraction and hypertrophic scarring. Phosphorylase kinase (PhK), expressed within 5 mins of injury, is among the earliest enzymes released after tissue damage. It is responsible for activation of NF-kB, which in turn activates over 200 different genes related to inflammation, fibroblastic proliferation, myofibroblast conversion, and eventual scar tissue formation. The sequence and approximate timing of events following injury include the following: activation of PhK (5 mins), followed by appearance of neutrophils (30 mins), macrophages (hours to days), fibroblasts (1 week) and myofibroblasts (2 weeks). Cytokines and growth factors secreted by macrophages include fibroblast growth factor (FGF) and transforming growth factors α and β (TGFα and TGFβ). Fibroblast growth factor is responsible for fibroblastic proliferation, and TGFβ1 for conversion of fibroblasts into myofibroblasts. After thermal injury, the use of topical curcumin, a non-competitive, selective PhK inhibitor that blocks PhK activity upstream of NF-kB activation, was found to be associated with more rapid and improved skin healing, as well as less severe or absent scarring.
tissue injury, thermal injury, hypertrophic scarring, fibroblast proliferation, myofibroblast conversion
Wound healing following significant burns and scalds almost always result in hypertrophic scarring. In general, all tissues after injury are acutely infiltrated by many cell types (
We found that one of the earliest cells activated by tissue injury is the Langerhans cell, the activation of which is detected within 5 mins of epidermal injury (
Activated fibroblasts infiltrate the wound about a week after injury. TGF-β, which is chemotactic to activated fibroblasts, also stimulates fibroblastic proliferation (
The transformation of fibroblasts into myofibroblasts, which usually occurs 2 weeks after injury, is probably the key event in the formation of hypertrophic scarring. Myofibroblasts express α-smooth muscle actin and possess contractile properties resembling smooth muscle, resulting in generation of the forces that lead to wound contraction and hypertrophic scarring (
The molecule induced by injury and central to the wound healing process appears to be the transcription activator, NF-kB, which is detected as early as 30 mins after injury (
Phosphorylase kinase is a dual specificity kinase capable of transferring high energy phosphate bonds to both serine/threonine and tyrosine specific substrates (28). Most protein kinases can only transfer high energy phosphate bonds to substrates of a single specificity i.e. either serine/threonine or tyrosine. Phosphorylase kinase is a unique enzyme in which the spatial arrangements of the specificity determinants can be manipulated so that PhK can transfer high energy phosphate bonds from ATP to substrates of different specificities, such as serine/threonine and tyrosine residues (
Curcumin, the active ingredient of the spice, turmeric, is a non-competitive selective PhK inhibitor (
The following cases illustrate examples of patients with burns and scalds treated with topical curcumin gel that resulted in rapid healing and minimal or absent scarring.
The patient is an 11 year old boy who sustained severe 2nd degree flash burns from pouring lighter fluid on warm barbeque coals. The heat from the ensuing fire singed his hair, eyelashes, forehead, ears, nose, cheeks and neck (Fig.
Burns from Barbeque Fire:
Burns from Barbeque Fire:
The patient was a 2-year old boy who sustained 2nd degree burns over the palms of both hands after falling into a camp-fire. He was seen at a number of emergency care centers, and treated with silvadene cream. When seen four days later, large blisters were seen over both palms (Fig.
Burns from a campfire see four days following injury, Note the presence of blisters suggesting at least second degree burns.
Improvement one day later after hourly application of curcumin gel. Pain and blistering were much improved.
Significant healing observed with curcumin gel (multiple applications daily) was observed after two weeks. Note rapid re-epithelialization of most of the skin of both palms. Also note inability of the patient to fully extend his fingers.
The patient, a 35-year old female, sustained scalds to her left hand when she accidentally poured boiling water over the left hand. When seen one day later, early blister formation, suggestive of second degree injury, was observed both over the left palm and palmar aspect of all the fingers of her left hand (Fig.
Scald from boiling water seen one day after injury before curcumin gel. Note the presence of early blister formation associated with significant pain. Note also the inability of the patient to fully extend her fingers.
Wounds in adults, unlike fetal wounds, often heal with scarring (
In this review, we report the clinical outcome of several patients with burns and scalds treated with curcumin gel that resulted in minimal scarring or scar-free healing. We have previously reported similar beneficial outcomes with use of curcumin gel in post-surgical scars (
We noted that application of curcumin gel after burns and scalds is usually followed by rapid decrease in erythema, blistering, swelling and pain. Improvement in these clinical symptoms and findings strongly suggests that cytokine activity, in particular TNFα, is reduced in curcumin-treated wounds. TNFα is an inflammatory cytokine produced by many activated cells, and especially inflammatory cells such as T lymphocytes and macrophages. TNFα levels have been shown to be significantly increased in burns and other types of injury. By blocking PhK activity (
Dr. Heng has shares in Omnicure Inc., a company that manufactures and markets topical curcumin gel.