Effect of gamma-hydroxybutyrate on keratinocytes proliferation: A preliminary prospective controlled study in severe burn patients

Abstract

Background:Hypermetabolism and hyposomatotropism related to severe burns lead to impaired wound healing. Growth hormone (GH) boosts wound healing notably following stimulation of the production of insulin-like growth factor-1 (IGF1), a mitogen factor for keratinocytes. Gamma-hydroxybutyrate (GHB) stimulates endogenous GH secretion.Aim:To assess effects of GHB sedation on keratinocytes proliferation (based on immunohistochemical techniques).Design:Monocentric, prospective, controlled trial.Materials and Methods:Patients (aging 18-65 years, burn surface area >30%, expected to be sedated for at least one month) were alternately allocated, at the 5th day following injury, in three groups according to the intravenous GHB dose administered for 21 days: Evening bolus of 50 mg/kg (Group B), continuous infusion at the rate of 10 mg/kg/h (Group C), or absence of GHB (Group P). They all received local standard cares. Immunohistochemistry (Ki67/MIB-1, Ulex europaeus agglutinin-1 and Mac 387 antibodies) was performed at D21 on adjacent unburned skin sample for assessing any keratinocyte activation. Serum IGF1 levels were measured at initiation and completion of the protocol.Statistical Analysis:Categorical variables were compared with Chi-square test. Comparisons of medians were made using Kruskal-Wallis test. Post hoc analyses were performed using Mann-Whitney test with Bonferroni correction for multiple comparisons. A P < 0.05 was considered to be statistically significant.Results:A total of 14 patients completed the study (Group B: n = 5, Group C: n = 5, Group P: n = 4). Continuous administration of GHB was associated with a significant higher Ki67 immunolabeling at D21 (P = 0.049) and with a significant higher increase in the IGF1 concentrations at D21 (P = 0.024). No adverse effects were disclosed.Conclusions:Our preliminary data support a positive effect of GHB on keratinocyte proliferation and are encouraging enough to warrant large prospective studies.

Toxicological Characterization of GHB as a Performance-Enhancing Drug

“…Interestingly, a GH release was also seen in animals affected by burn wounds for a total body surface over 40%, in which wound morphology analysis testified a more rapid healing process (epithelialization rates and layer thickness) under high doses of GHB treatment compared with controls ( 32 ). Higher keratinocytes proliferation rates were also found in humans with severe burn injuries ( 41 ). It has to be underlined that, in the context of athletic performances, a potential for the use of GHB might arise from this skin wound healing effect, once confirmed on a larger scale.…”

Protomyofibroblast Pathway in Early Thermal Burn Healing

“…It represented in part an extension to two previous investigations about thermal burn healing [28,29]. A total of 25 burn patients (21 men and 4 women) were enrolled over 9 years.…”

Gamma-hydroxybutyrate and keratinocytes proliferation (correspondence to Int J Crit Illn Inj Sci 2014;2:108-13)

“…A recent report on “gamma-hydroxybutyrate (GHB) and keratinocytes proliferation”[ 1 ] is very interesting. Rousseau et al ., assessed the “effects of GHB sedation on keratinocytes proliferation”[ 1 ] and noted “a positive effect of GHB on keratinocyte proliferation”.…”

“…A recent report on “gamma-hydroxybutyrate (GHB) and keratinocytes proliferation”[ 1 ] is very interesting. Rousseau et al ., assessed the “effects of GHB sedation on keratinocytes proliferation”[ 1 ] and noted “a positive effect of GHB on keratinocyte proliferation”. [ 1 ] Murphy et al ., previously mentioned for the possible effect of GHB on growth hormone system and mentioned its usefulness in wound healing.…”

“…Rousseau et al ., assessed the “effects of GHB sedation on keratinocytes proliferation”[ 1 ] and noted “a positive effect of GHB on keratinocyte proliferation”. [ 1 ] Murphy et al ., previously mentioned for the possible effect of GHB on growth hormone system and mentioned its usefulness in wound healing. [ 2 ] To apply GHB use in injury science is interesting, however, the possible adverse effect of GHB should be mentioned.…”