The effect of KUS121, a novel VCP modulator, against ischemic injury in random pattern flaps.
Surgery using skin flaps is essential for soft tissue reconstruction. However, postoperative ischemic injury of the skin flap is a major complication and a top concern after the surgery. Currently, evidence-based drugs to fully prevent ischemic injury are not available. The purpose of this study was...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0299882 |
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| author | Koichi Yoshimoto Ryosuke Ikeguchi Takashi Noguchi Maki Ando Daichi Sakamoto Terunobu Iwai Kohei Nishitani Hanako Ohashi Ikeda Akira Kakizuka Shuichi Matsuda |
| author_facet | Koichi Yoshimoto Ryosuke Ikeguchi Takashi Noguchi Maki Ando Daichi Sakamoto Terunobu Iwai Kohei Nishitani Hanako Ohashi Ikeda Akira Kakizuka Shuichi Matsuda |
| author_sort | Koichi Yoshimoto |
| collection | DOAJ |
| description | Surgery using skin flaps is essential for soft tissue reconstruction. However, postoperative ischemic injury of the skin flap is a major complication and a top concern after the surgery. Currently, evidence-based drugs to fully prevent ischemic injury are not available. The purpose of this study was to evaluate the effect of KUS121, a VCP modulator, on flap ischemia using a rodent model. 26 Sprague-Dawley rats were randomly divided into two groups. The experimental group was intraperitoneally administered with 100 mg/kg KUS121 dissolved in 5% glucose solution 1 hour before surgery and once per day after surgery. The control group received the same amount of glucose solution on the same schedule. On day 7, 33.6 ± 3.7% of skin flaps in the control group had developed black necrosis compared with 26.4 ± 3.6% in the KUS121 group (p < 0.01). Immunohistochemistry showed that the KUS121 treatment reduced the number of apoptotic cells in the distal third of the flap (p < 0.01); moreover, in the KUS121-treated rats, the number of cells expressing CHOP, an endoplasmic reticulum (ER) stress marker, in the middle third of the flap was significantly lower than in the controls (p < 0.01). We examined the mRNA expression of Ddit3 (CHOP) and Casp3 (caspase-3) on day one after the surgery; mRNA expression of both genes appeared to decrease in the KUS121 group, as compared with the control group, although differences between groups were not significant. Thus, in a random pattern flap, KUS121 reduces ER stress and the number of apoptotic cells, thereby reducing ischemic damage of the flap. |
| format | Article |
| id | doaj-art-30accd22951e4b6d97afe20933e62b42 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-30accd22951e4b6d97afe20933e62b422025-01-08T05:32:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011912e029988210.1371/journal.pone.0299882The effect of KUS121, a novel VCP modulator, against ischemic injury in random pattern flaps.Koichi YoshimotoRyosuke IkeguchiTakashi NoguchiMaki AndoDaichi SakamotoTerunobu IwaiKohei NishitaniHanako Ohashi IkedaAkira KakizukaShuichi MatsudaSurgery using skin flaps is essential for soft tissue reconstruction. However, postoperative ischemic injury of the skin flap is a major complication and a top concern after the surgery. Currently, evidence-based drugs to fully prevent ischemic injury are not available. The purpose of this study was to evaluate the effect of KUS121, a VCP modulator, on flap ischemia using a rodent model. 26 Sprague-Dawley rats were randomly divided into two groups. The experimental group was intraperitoneally administered with 100 mg/kg KUS121 dissolved in 5% glucose solution 1 hour before surgery and once per day after surgery. The control group received the same amount of glucose solution on the same schedule. On day 7, 33.6 ± 3.7% of skin flaps in the control group had developed black necrosis compared with 26.4 ± 3.6% in the KUS121 group (p < 0.01). Immunohistochemistry showed that the KUS121 treatment reduced the number of apoptotic cells in the distal third of the flap (p < 0.01); moreover, in the KUS121-treated rats, the number of cells expressing CHOP, an endoplasmic reticulum (ER) stress marker, in the middle third of the flap was significantly lower than in the controls (p < 0.01). We examined the mRNA expression of Ddit3 (CHOP) and Casp3 (caspase-3) on day one after the surgery; mRNA expression of both genes appeared to decrease in the KUS121 group, as compared with the control group, although differences between groups were not significant. Thus, in a random pattern flap, KUS121 reduces ER stress and the number of apoptotic cells, thereby reducing ischemic damage of the flap.https://doi.org/10.1371/journal.pone.0299882 |
| spellingShingle | Koichi Yoshimoto Ryosuke Ikeguchi Takashi Noguchi Maki Ando Daichi Sakamoto Terunobu Iwai Kohei Nishitani Hanako Ohashi Ikeda Akira Kakizuka Shuichi Matsuda The effect of KUS121, a novel VCP modulator, against ischemic injury in random pattern flaps. PLoS ONE |
| title | The effect of KUS121, a novel VCP modulator, against ischemic injury in random pattern flaps. |
| title_full | The effect of KUS121, a novel VCP modulator, against ischemic injury in random pattern flaps. |
| title_fullStr | The effect of KUS121, a novel VCP modulator, against ischemic injury in random pattern flaps. |
| title_full_unstemmed | The effect of KUS121, a novel VCP modulator, against ischemic injury in random pattern flaps. |
| title_short | The effect of KUS121, a novel VCP modulator, against ischemic injury in random pattern flaps. |
| title_sort | effect of kus121 a novel vcp modulator against ischemic injury in random pattern flaps |
| url | https://doi.org/10.1371/journal.pone.0299882 |
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