Botulinum toxin B suppresses the pressure ulcer formation in cutaneous ischemia-reperfusion injury mouse model: Possible regulation of oxidative and endoplasmic reticulum stress.

Abstract

BACKGROUND:

We previously identified that botulinum toxin A (BTX-A) suppressed pressure ulcer (PU) formation after cutaneous ischemia-reperfusion (I/R) injury; however, regulation of cutaneous I/R-induced oxidative and endoplasmic reticulum (ER) stress by BTX-B was not investigated. Additionally, the efficacy of BTX-B injection has never been examined.

OBJECTIVE:

Objective was to assess the effects of BTX-B on the formation of PU by cutaneous I/R injury, and the regulation of oxidative and ER stress in I/R injury by BTX-B.

METHODS:

BTX-B was subcutaneously injected into I/R area, and wound size, vascular damage, hypoxic area, and apoptotic cells in I/R area were analyzed. We evaluated the extent of oxidative and ER stress in I/R area by using OKD48 mice and ERAI mice, respectively, which enabled evaluating oxidative and ER stress through bioluminescence detection.

RESULTS:

BTX-B injection significantly suppressed the formation of PU by cutaneous I/R injury. Cutaneous I/R-induced vascular damage, hypoxic area, and number of oxidative-damaged cells and apoptotic cells were suppressed by BTX-B injection. BTX-B administration significantly inhibited I/R-induced oxidative stress signal in OKD48 mice. BTX-B reduced the I/R-induced oxidative stress-associated factors. BTX-B significantly inhibited the oxidant-induced reactive oxygen species and apoptosis of endothelial cells and fibroblasts. BTX-B significantly inhibited I/R-induced ER stress signal in ERAI mice. Cutaneous I/R injury-induced ER stress-response factors and GRP78/BiP and CHOP-positive cells in I/R area were significantly decreased by BTX-B injection.

CONCLUSION:

BTX-B injection might have protective effects against PU formation after cutaneous I/R injury by reducing vascular damage, hypoxia-induced oxidative and ER stress, and apoptosis.

• Authors: Akiko Sekiguchi, Sei-Ichiro Motegi, Akihiko Uchiyama, Akihito Uehara, Chisako Fujiwara, Sahori Yamazaki, Buddhini Perera, Hideharu Nakamura, Sachiko Ogino, Yoko Yokoyama, Ryoko Akai, Takao Iwawaki, Osamu Ishikawa
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 90 Issue 2 Pg. 144-153 (May 2018) ISSN: 1873-569X [Electronic] Netherlands
• PMID: 29402605 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Hspa5 protein, mouse
• Oxidants
• Reactive Oxygen Species
• rimabotulinumtoxinB
• Botulinum Toxins, Type A

Topics

• Animals
• Apoptosis (drug effects)
• Botulinum Toxins, Type A (pharmacology, therapeutic use)
• Disease Models, Animal
• Endoplasmic Reticulum Chaperone BiP
• Endoplasmic Reticulum Stress (drug effects)
• Fibroblasts
• Human Umbilical Vein Endothelial Cells
• Humans
• Injections, Subcutaneous
• Mice
• Mice, Inbred C57BL
• NIH 3T3 Cells
• Oxidants (pharmacology)
• Oxidative Stress (drug effects)
• Pressure Ulcer (drug therapy, etiology, pathology)
• Reactive Oxygen Species (metabolism)
• Reperfusion Injury (complications, pathology)
• Skin (blood supply, drug effects, pathology)
• Treatment Outcome