Efficacy of leupeptin in treating ischemia in a rat hind limb model
Abstract Prolonged tourniquet use can lead to tissue ischemia and can cause progressive muscle and nerve injuries. Such injuries are accompanied by calpain activation and subsequent Wallerian‐like degeneration. Several known inhibitors, including leupeptin, are known to impede the activity of calpai...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-08-01
|
| Series: | Physiological Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.14814/phy2.15411 |
| _version_ | 1797397306631258112 |
|---|---|
| author | Mikhail Gurevich Kari Iocolano Irene Nozal Martin Gurtej Singh Sami U. Khan Duc T. Bui Alexander B. Dagum David E. Komatsu |
| author_facet | Mikhail Gurevich Kari Iocolano Irene Nozal Martin Gurtej Singh Sami U. Khan Duc T. Bui Alexander B. Dagum David E. Komatsu |
| author_sort | Mikhail Gurevich |
| collection | DOAJ |
| description | Abstract Prolonged tourniquet use can lead to tissue ischemia and can cause progressive muscle and nerve injuries. Such injuries are accompanied by calpain activation and subsequent Wallerian‐like degeneration. Several known inhibitors, including leupeptin, are known to impede the activity of calpain and associated tissue damage. We hypothesize that employment of leupeptin in a rat model of prolonged hind limb ischemia can mitigate muscle and nerve injuries. Sprague–Dawley rats (n = 10) weighing between 300–400 g were employed in this study. Their left hind limbs were subjected to blood flow occlusion for a period of 2‐h using a neonatal blood pressure cuff. Five rats were given twice weekly intramuscular leupeptin injections, while the other five received saline. After 2 weeks, the animals were euthanized, their sciatic nerves and gastrocnemius muscles were harvested, fixed, stained, and analyzed using NIH Image J software. The administration of leupeptin resulted in larger gastrocnemius muscle fiber cross‐sectional areas for the right (non‐tourniquet applied) hindlimb as compared to that treated with the saline (p = 0.0110). However, no statistically significant differences were found between these two groups for the injured left hindlimb (p = 0.1440). With regards to the sciatic nerve cross‐sectional areas and sciatic functional index, no differences were detected between the leupeptin and control treated groups for both the healthy and injured hindlimbs. This research provides new insights on how to employ leupeptin to inhibit the degenerative effects of calpain and preserve tissues following ischemia resulting from orthopedic or plastic surgery procedures. |
| first_indexed | 2024-03-09T01:08:57Z |
| format | Article |
| id | doaj.art-c65009e583fb408b8b87bc6673c47e0a |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-03-09T01:08:57Z |
| publishDate | 2022-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-c65009e583fb408b8b87bc6673c47e0a2023-12-11T09:10:41ZengWileyPhysiological Reports2051-817X2022-08-011015n/an/a10.14814/phy2.15411Efficacy of leupeptin in treating ischemia in a rat hind limb modelMikhail Gurevich0Kari Iocolano1Irene Nozal Martin2Gurtej Singh3Sami U. Khan4Duc T. Bui5Alexander B. Dagum6David E. Komatsu7Renaissance School of Medicine Stony Brook New York USAStony Brook University Stony Brook New York USADivision of Plastic and Reconstructive Surgery, Department of Surgery Stony Brook University Hospital Stony Brook New York USADivision of Plastic and Reconstructive Surgery, Department of Surgery Stony Brook University Hospital Stony Brook New York USADivision of Plastic and Reconstructive Surgery, Department of Surgery Stony Brook University Hospital Stony Brook New York USADivision of Plastic and Reconstructive Surgery, Department of Surgery Stony Brook University Hospital Stony Brook New York USADivision of Plastic and Reconstructive Surgery, Department of Surgery Stony Brook University Hospital Stony Brook New York USADepartment of Orthopaedics and Rehabilitation Stony Brook University Hospital New York USAAbstract Prolonged tourniquet use can lead to tissue ischemia and can cause progressive muscle and nerve injuries. Such injuries are accompanied by calpain activation and subsequent Wallerian‐like degeneration. Several known inhibitors, including leupeptin, are known to impede the activity of calpain and associated tissue damage. We hypothesize that employment of leupeptin in a rat model of prolonged hind limb ischemia can mitigate muscle and nerve injuries. Sprague–Dawley rats (n = 10) weighing between 300–400 g were employed in this study. Their left hind limbs were subjected to blood flow occlusion for a period of 2‐h using a neonatal blood pressure cuff. Five rats were given twice weekly intramuscular leupeptin injections, while the other five received saline. After 2 weeks, the animals were euthanized, their sciatic nerves and gastrocnemius muscles were harvested, fixed, stained, and analyzed using NIH Image J software. The administration of leupeptin resulted in larger gastrocnemius muscle fiber cross‐sectional areas for the right (non‐tourniquet applied) hindlimb as compared to that treated with the saline (p = 0.0110). However, no statistically significant differences were found between these two groups for the injured left hindlimb (p = 0.1440). With regards to the sciatic nerve cross‐sectional areas and sciatic functional index, no differences were detected between the leupeptin and control treated groups for both the healthy and injured hindlimbs. This research provides new insights on how to employ leupeptin to inhibit the degenerative effects of calpain and preserve tissues following ischemia resulting from orthopedic or plastic surgery procedures.https://doi.org/10.14814/phy2.15411calpainischemialeupeptinstourniquetsvascular system injuries |
| spellingShingle | Mikhail Gurevich Kari Iocolano Irene Nozal Martin Gurtej Singh Sami U. Khan Duc T. Bui Alexander B. Dagum David E. Komatsu Efficacy of leupeptin in treating ischemia in a rat hind limb model Physiological Reports calpain ischemia leupeptins tourniquets vascular system injuries |
| title | Efficacy of leupeptin in treating ischemia in a rat hind limb model |
| title_full | Efficacy of leupeptin in treating ischemia in a rat hind limb model |
| title_fullStr | Efficacy of leupeptin in treating ischemia in a rat hind limb model |
| title_full_unstemmed | Efficacy of leupeptin in treating ischemia in a rat hind limb model |
| title_short | Efficacy of leupeptin in treating ischemia in a rat hind limb model |
| title_sort | efficacy of leupeptin in treating ischemia in a rat hind limb model |
| topic | calpain ischemia leupeptins tourniquets vascular system injuries |
| url | https://doi.org/10.14814/phy2.15411 |
| work_keys_str_mv | AT mikhailgurevich efficacyofleupeptinintreatingischemiainarathindlimbmodel AT kariiocolano efficacyofleupeptinintreatingischemiainarathindlimbmodel AT irenenozalmartin efficacyofleupeptinintreatingischemiainarathindlimbmodel AT gurtejsingh efficacyofleupeptinintreatingischemiainarathindlimbmodel AT samiukhan efficacyofleupeptinintreatingischemiainarathindlimbmodel AT ductbui efficacyofleupeptinintreatingischemiainarathindlimbmodel AT alexanderbdagum efficacyofleupeptinintreatingischemiainarathindlimbmodel AT davidekomatsu efficacyofleupeptinintreatingischemiainarathindlimbmodel |