PMID- 33515165
OWN - NLM
STAT- MEDLINE
DCOM- 20210917
LR  - 20220130
IS  - 2212-5469 (Electronic)
IS  - 1738-2696 (Print)
IS  - 1738-2696 (Linking)
VI  - 18
IP  - 1
DP  - 2021 Feb
TI  - Nitric Oxide Produced by the Antioxidant Activity of Verapamil Improves the Acute 
      Wound Healing Process.
PG  - 179-186
LID - 10.1007/s13770-020-00308-x [doi]
AB  - BACKGROUND: Verapamil is used in the treatment of hypertension, angina pectoris, 
      cardiac arrhythmia, hypertrophic scars, and keloids to block transmembrane 
      calcium ion flux. Verapamil has antioxidant activity, which enhances the 
      production of nitric oxide (NO). NO promotes the proliferation of fibroblasts, 
      keratinocytes, endothelial cells, and epithelial cells during wound healing. In 
      this study, we investigated the effect of verapamil and its antioxidant 
      properties on the enhancement of acute wound healing via NO. METHODS: A 
      full-thickness wound healing model was created on the rat dorsal with a silicone 
      ring. The wound closure rate was estimated every 2 days for 14 days. A 
      histological study was performed to evaluate wound healing. Immunofluorescence 
      staining was analyzed for angiogenesis. The expressions of collagen type I (COL 
      I), collagen type III (COL III), and vascular endothelial growth factor (VEGF) 
      were assessed by Western blot. Real-time polymerase chain reaction (qRT-PCR) was 
      performed to examine the expression of endothelial NO synthase and inducible NO 
      synthase, which are related to antioxidant activity in the process of wound 
      healing. RESULTS: The wound closure rate was faster in the verapamil group 
      compared to the control and silicone groups. Histologic analysis revealed 
      capillaries and stratum basale in the verapamil group. Immunofluorescence 
      staining was shown vessel formation in the verapamil group. Western blot and 
      qRT-PCR analysis revealed high expression levels of COL I, VEGF, eNOS, and FGF in 
      the verapamil. CONCLUSION: Verapamil's antioxidant activity enhances NO 
      production in acute wound healing. We suggest that verapamil can be used to 
      promote acute wound healing.
FAU - Han, Yu Na
AU  - Han YN
AD  - Department of Biomedicine and Health Sciences, College of Medicine, The Catholic 
      University of Korea, 222 Banpo-daero, Seoul, 06591, Republic of Korea.
AD  - Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul St. 
      Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, 
      Seoul, 06591, Republic of Korea.
FAU - Lee, Yoon Jae
AU  - Lee YJ
AD  - Department of Plastic and Reconstructive Surgery, College of Medicine, Yeouido 
      St. Mary's Hospital, The Catholic University of Korea, 1661-7575, 
      Yeongdeungpo-gu, Seoul, Republic of Korea.
FAU - Kim, Ki Joo
AU  - Kim KJ
AD  - Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul St. 
      Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, 
      Seoul, 06591, Republic of Korea.
FAU - Lee, Su Jin
AU  - Lee SJ
AD  - Department of Biomedicine and Health Sciences, College of Medicine, The Catholic 
      University of Korea, 222 Banpo-daero, Seoul, 06591, Republic of Korea.
AD  - Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul St. 
      Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, 
      Seoul, 06591, Republic of Korea.
FAU - Choi, Jang Youn
AU  - Choi JY
AD  - Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul St. 
      Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, 
      Seoul, 06591, Republic of Korea.
FAU - Moon, Suk-Ho
AU  - Moon SH
AD  - Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul St. 
      Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, 
      Seoul, 06591, Republic of Korea.
FAU - Rhie, Jong Won
AU  - Rhie JW
AUID- ORCID: 0000-0002-9398-8059
AD  - Department of Biomedicine and Health Sciences, College of Medicine, The Catholic 
      University of Korea, 222 Banpo-daero, Seoul, 06591, Republic of Korea. 
      rhie@catholic.ac.kr.
AD  - Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul St. 
      Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, 
      Seoul, 06591, Republic of Korea. rhie@catholic.ac.kr.
LA  - eng
GR  - 2017M3A9E2060428/National Research Foundation of Korea/
GR  - 10062127/Korea Evaluation Institute of Industrial Technology/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210129
PL  - Korea (South)
TA  - Tissue Eng Regen Med
JT  - Tissue engineering and regenerative medicine
JID - 101699923
RN  - 0 (Antioxidants)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - CJ0O37KU29 (Verapamil)
SB  - IM
MH  - Animals
MH  - *Antioxidants/pharmacology
MH  - Endothelial Cells
MH  - *Nitric Oxide
MH  - Rats
MH  - Vascular Endothelial Growth Factor A
MH  - Verapamil/pharmacology
MH  - Wound Healing
PMC - PMC7862477
OTO - NOTNLM
OT  - Antioxidant activity
OT  - Nitric oxide
OT  - Verapamil
OT  - Wound healing
COIS- The authors have no financial conflicts of interest.
EDAT- 2021/01/31 06:00
MHDA- 2021/09/18 06:00
PMCR- 2022/01/29
CRDT- 2021/01/30 05:36
PHST- 2020/06/22 00:00 [received]
PHST- 2020/10/13 00:00 [accepted]
PHST- 2020/09/17 00:00 [revised]
PHST- 2021/01/31 06:00 [pubmed]
PHST- 2021/09/18 06:00 [medline]
PHST- 2021/01/30 05:36 [entrez]
PHST- 2022/01/29 00:00 [pmc-release]
AID - 10.1007/s13770-020-00308-x [pii]
AID - 308 [pii]
AID - 10.1007/s13770-020-00308-x [doi]
PST - ppublish
SO  - Tissue Eng Regen Med. 2021 Feb;18(1):179-186. doi: 10.1007/s13770-020-00308-x. 
      Epub 2021 Jan 29.