Effects of Folinic Acid Administration on Lower Limb Ischemia/Reperfusion Injury in Rats
Surgery under ischemic conditions, lasting up to 3 h, is routinely performed in orthopedic surgery, causing undesirable injury due to ischemia-reperfusion syndrome, with short and medium-term functional repercussions. To date, there is no established prophylactic treatment. In this work we evaluated...
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| Format: | Article |
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MDPI AG
2021-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/12/1887 |
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| author | Iñigo Cearra Borja Herrero de la Parte Inmaculada Ruiz Montesinos Ana Alonso-Varona Diana Isabel Moreno-Franco Ignacio García-Alonso |
| author_facet | Iñigo Cearra Borja Herrero de la Parte Inmaculada Ruiz Montesinos Ana Alonso-Varona Diana Isabel Moreno-Franco Ignacio García-Alonso |
| author_sort | Iñigo Cearra |
| collection | DOAJ |
| description | Surgery under ischemic conditions, lasting up to 3 h, is routinely performed in orthopedic surgery, causing undesirable injury due to ischemia-reperfusion syndrome, with short and medium-term functional repercussions. To date, there is no established prophylactic treatment. In this work we evaluated folinic acid (FA) in a rodent model of lower limb ischemia-reperfusion (IRI-LL). 36 male WAG rats underwent 3 h of lower limb ischemia. In the saline group, rats received intraperitoneal administration of saline (used as vehicle for treatment). In the experimental group, rats were pretreated with FA (2.5 mg/kg) before the end of ischemia. After ischemia, animals were sacrificed at 3 h, 24 h or 14 days (for biochemical determination (Na+, K+, Cl-, urea, creatinine, CK, LDH, ALP, ALT, and AST), pathological assessment, or functional study using the rotarod test; respectively). Another six animals were used to establish the reference values. The prophylactic administration of FA significantly reduced the elevation of biochemical markers, especially those that most directly indicate muscle damage (CK and LDH). In addition, it also improved direct tissue damage, both in terms of edema, weight, PMN infiltrate and percentage of damaged fibers. Finally, the administration of FA allowed the animals to equal baseline values in the rotarod test; what did not occur in the saline group, where pre-ischemia levels were not recovered. Following 3 h of lower limb ischemia, FA minimizes the increase of CK and LDH, as well as local edema and leukocyte infiltration, allowing a faster recovery of limb functionality. Therefore, it could be considered as a prophylactic treatment when tourniquet is used in clinics. |
| first_indexed | 2024-03-10T04:38:26Z |
| format | Article |
| id | doaj.art-4219e0bc1db6408482a5b3eef87e6b85 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T04:38:26Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-4219e0bc1db6408482a5b3eef87e6b852023-11-23T03:32:28ZengMDPI AGAntioxidants2076-39212021-11-011012188710.3390/antiox10121887Effects of Folinic Acid Administration on Lower Limb Ischemia/Reperfusion Injury in RatsIñigo Cearra0Borja Herrero de la Parte1Inmaculada Ruiz Montesinos2Ana Alonso-Varona3Diana Isabel Moreno-Franco4Ignacio García-Alonso5Osakidetza Basque Health Service, Department of Traumatology and Orthopedics, Basurto University Hospital, ES48013 Bilbao, SpainDepartment of Surgery and Radiology and Physical Medicine, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, ES48940 Leioa, SpainDepartment of Surgery and Radiology and Physical Medicine, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, ES48940 Leioa, SpainDepartment of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, ES48940 Leioa, SpainOsakidetza Basque Health Service, Department of Vascular Surgery and Angiology, Basurto University Hospital, ES48013 Bilbao, SpainDepartment of Surgery and Radiology and Physical Medicine, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, ES48940 Leioa, SpainSurgery under ischemic conditions, lasting up to 3 h, is routinely performed in orthopedic surgery, causing undesirable injury due to ischemia-reperfusion syndrome, with short and medium-term functional repercussions. To date, there is no established prophylactic treatment. In this work we evaluated folinic acid (FA) in a rodent model of lower limb ischemia-reperfusion (IRI-LL). 36 male WAG rats underwent 3 h of lower limb ischemia. In the saline group, rats received intraperitoneal administration of saline (used as vehicle for treatment). In the experimental group, rats were pretreated with FA (2.5 mg/kg) before the end of ischemia. After ischemia, animals were sacrificed at 3 h, 24 h or 14 days (for biochemical determination (Na+, K+, Cl-, urea, creatinine, CK, LDH, ALP, ALT, and AST), pathological assessment, or functional study using the rotarod test; respectively). Another six animals were used to establish the reference values. The prophylactic administration of FA significantly reduced the elevation of biochemical markers, especially those that most directly indicate muscle damage (CK and LDH). In addition, it also improved direct tissue damage, both in terms of edema, weight, PMN infiltrate and percentage of damaged fibers. Finally, the administration of FA allowed the animals to equal baseline values in the rotarod test; what did not occur in the saline group, where pre-ischemia levels were not recovered. Following 3 h of lower limb ischemia, FA minimizes the increase of CK and LDH, as well as local edema and leukocyte infiltration, allowing a faster recovery of limb functionality. Therefore, it could be considered as a prophylactic treatment when tourniquet is used in clinics.https://www.mdpi.com/2076-3921/10/12/1887ischemia-reperfusion injurylower limbtourniquetfolinic acidprophylactic treatmentfunctional recovery |
| spellingShingle | Iñigo Cearra Borja Herrero de la Parte Inmaculada Ruiz Montesinos Ana Alonso-Varona Diana Isabel Moreno-Franco Ignacio García-Alonso Effects of Folinic Acid Administration on Lower Limb Ischemia/Reperfusion Injury in Rats Antioxidants ischemia-reperfusion injury lower limb tourniquet folinic acid prophylactic treatment functional recovery |
| title | Effects of Folinic Acid Administration on Lower Limb Ischemia/Reperfusion Injury in Rats |
| title_full | Effects of Folinic Acid Administration on Lower Limb Ischemia/Reperfusion Injury in Rats |
| title_fullStr | Effects of Folinic Acid Administration on Lower Limb Ischemia/Reperfusion Injury in Rats |
| title_full_unstemmed | Effects of Folinic Acid Administration on Lower Limb Ischemia/Reperfusion Injury in Rats |
| title_short | Effects of Folinic Acid Administration on Lower Limb Ischemia/Reperfusion Injury in Rats |
| title_sort | effects of folinic acid administration on lower limb ischemia reperfusion injury in rats |
| topic | ischemia-reperfusion injury lower limb tourniquet folinic acid prophylactic treatment functional recovery |
| url | https://www.mdpi.com/2076-3921/10/12/1887 |
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