Botulinum toxin A increases allograft tolerance in an experimental transplantation model: a preliminary study

Abstract

BackgroundIdentifying novel and safe immunosuppressants is of crucial importance. Recently, there have been several studies revealing that botulinum toxin A significantly alleviates ischemia-reperfusion injuries.Emerging evidence shows that ischemia-reperfusion injuries contribute to innate immune activation, promoting rejection and inhibiting tolerance. Therefore, we hypothesized that a pretreatment with botulinum toxin A might decrease allograft rejection in a rat transplantation model. MethodsTwenty-four Lewis rats were randomly assigned to two groups consisting of 12 rats each, depending on whether skin allograft was performed after pretreatment with botulinum toxin A (BoTA group) or with normal saline (control group). The experimental group was pretreated with a subcutaneous injection of botulinum toxin A (10 IU), while the control group was pretreated with normal saline 5 days prior to surgery. The donor Brown-Norway rat dorsal skin was subsequently grafted to the recipient Lewis rats. The recipient wounds, measuring 2 cm × 2 cm, were made via dorsal skin excision through the panniculus carnosus. The donor skins of the same dimensions were obtained and transplanted onto the wounds and sutured with 4-0 nylon sutures. Mean graft survival time was measured in both groups. Quantitative reverse-transcriptase polymerase chain reaction and western blotting were performed to evaluate the gene/protein expression of CD4 and VEGF. ResultsThe mean graft survival time in the BoTA group was significantly longer than that of the control group (p=0.004). The relative mRNA and protein expression of CD4 was significantly lower in the BoTA group (p<0.001), while the relative mRNA and protein expression of VEGF was significantly higher in the BoTA group (p<0.001). ConclusionIn conclusion, our results show that botulinum toxin A prolongs the survival of skin allografts in a rat transplantation model.

Effects of Botulinum Toxin Type A on Microvessels in Hypertrophic Scar Models on Rabbit Ears

“…Park and Park [30] demonstrated that BTXA treatment might increase the expression of VEGF and yield protection against ischemiareperfusion injury depending on increasing angiogenesis. Other studies also concluded that the group with BTXA treatment had higher VEGF expression in a rat transplantation model or transverse rectus abdominis myocutaneous flap in a rat model [31,32]. The concentration of BTXA used in these studies was 10 IU/mL, but Gugerell et al [33] found that high BTXA concentration of 20 IU/mL might reduce VEGF expression and inhibit angiogenesis.…”

Practical context of enzymatic treatment for wound healing: A secreted protease approach (Review)

“…Nevertheless, studies on SP-aided transplants is still ambiguous. For example, the use of botulinum toxin A during skin transplantation in murine models enhances the expression of VEGF and prolonged the survival of skin grafts (148). By contrast, Kucukkaya et al (149) demonstrated that the same toxin reduces wound-graft contraction.…”

Gene signature and prediction model of the mitophagy-associated immune microenvironment in renal ischemia-reperfusion injury

“…Renal tubular epithelial cells are the cells most severely damaged in response to IRI ( 8 ). IRI results in the loss of tubular epithelial cell function, leading to acute renal injury, delayed graft function, and acute and chronic organ rejection ( 9 , 10 ). Mitochondrial autophagy and ferroptosis also occur in renal tubules in response to IRI ( 11 , 12 ).…”